ABSTRACT
Pyroptosis represents a type of cell death mechanism notable for its cell membrane disruption and the subsequent release of proinflammatory cytokines. The Nod-like receptor family pyrin domain containing inflammasome 3 (NLRP3) plays a critical role in the pyroptosis mechanism associated with various diseases resulting from particulate matter (PM) exposure. Tert-butylhydroquinone (tBHQ) is a synthetic antioxidant commonly used in a variety of foods and products. The aim of this study is to examine the potential of tBHQ as a therapeutic agent for managing sinonasal diseases induced by PM exposure. The occurrence of NLRP3 inflammasome-dependent pyroptosis in RPMI 2650 cells treated with PM < 4 µm in size was confirmed using Western blot analysis and enzyme-linked immunosorbent assay results for the pyroptosis metabolites IL-1ß and IL-18. In addition, the inhibitory effect of tBHQ on PM-induced pyroptosis was confirmed using Western blot and immunofluorescence techniques. The inhibition of tBHQ-mediated pyroptosis was abolished upon nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown, indicating its involvement in the antioxidant mechanism. tBHQ showed potential as a therapeutic agent for sinonasal diseases induced by PM because NLRP3 inflammasome activation was effectively suppressed via the Nrf2 pathway.
ABSTRACT
In this paper, we investigate the structural, microstructural, dielectric, and energy storage properties of Nd and Mn co-doped Ba0.7Sr0.3TiO3 [(Ba0.7Sr0.3)1-xNdxTi1-yMnyO3 (BSNTM) ceramics (x = 0, 0.005, and y = 0, 0.0025, 0.005, and 0.01)] via a defect dipole engineering method. The complex defect dipoles (MnTi"-VOââ)â and (MnTi"-VOââ) between acceptor ions and oxygen vacancies capture electrons, enhancing the breakdown electric field and energy storage performances. XRD, Raman, spectroscopy, XPS, and microscopic investigations of BSNTM ceramics revealed the formation of a tetragonal phase, oxygen vacancies, and a reduction in grain size with Mn dopant. The BSNTM ceramics with x = 0.005 and y = 0 exhibit a relative dielectric constant of 2058 and a loss tangent of 0.026 at 1 kHz. These values gradually decreased to 1876 and 0.019 for x = 0.005 and y = 0.01 due to the Mn2+ ions at the Ti4+- site, which facilitates the formation of oxygen vacancies, and prevents a decrease in Ti4+. In addition, the defect dipoles act as a driving force for depolarization to tailor the domain formation energy and domain wall energy, which provides a high difference between the maximum polarization of Pmax and remnant polarization of Pr (ΔP = 10.39 µC/cm2). Moreover, the complex defect dipoles with optimum oxygen vacancies in BSNTM ceramics can provide not only a high ΔP but also reduce grain size, which together improve the breakdown strength from 60.4 to 110.6 kV/cm, giving rise to a high energy storage density of 0.41 J/cm3 and high efficiency of 84.6% for x = 0.005 and y = 0.01. These findings demonstrate that defect dipole engineering is an effective method to enhance the energy storage performance of dielectrics for capacitor applications.
ABSTRACT
The unilateral ureteral obstruction (UUO) injury model is well-known to mimic human chronic kidney disease, promoting the rapid onset and development of kidney injury. ω3-poly unsaturated fatty acids (PUFAs) have been observed to protect against tissue injury in many disease models. In this study, we assessed the efficacy of ω3-PUFAs in attenuating UUO injury and investigated their mechanism of action. The immortalized human proximal tubular cells human kidney-2 (HK2) were incubated for 72 h with docosahexaenoic acid (DHA) or eicosapentaenoic acid (EPA) in various concentrations, in the presence or absence of transforming growth factor (TGF)-ß. DHA/EPA reduced the epithelial-mesenchymal transition in the TGF-ß-treated HK2 cells by enhancing autophagy flux and adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. C57BL/6 mice were divided into four groups and treated as follows: sham (no treatment, n = 5), sham + ω3-PUFAs (n = 5), UUO (n = 10), and UUO + ω3-PUFAs (n = 10). Their kidneys and blood were harvested on the seventh day following UUO injury. The kidneys of the ω3-PUFAs-treated UUO mice showed less oxidative stress, inflammation, and fibrosis compared to those of the untreated UUO mice. Greater autophagic flux, higher amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7, lower amounts of p62, and higher levels of cathepsin D and ATP6E were observed in the kidneys of the omega-3-treated UUO mice compared to those of the control UUO mice. In conclusion, ω3-PUFAs enhanced autophagic activation, leading to a renoprotective response against chronic kidney injury.
ABSTRACT
In patients with chronic kidney disease, the need for examinations using contrast media (CM) increases because of underlying diseases. Although contrast agents can affect brain cells, the blood-brain barrier (BBB) protects against brain-cell damage in vivo. However, uremia can disrupt the BBB, increasing the possibility of contrast-agent-induced brain-cell damage in patients with chronic kidney disease (CKD). ω-3 polyunsaturated fatty acids (PUFAs) have shown protective effects on various neurological disorders, including uremic brain injury. This study examined whether ω-3 PUFAs attenuate damage to the BBB caused by uremia and contrast agents in a uremic mouse model and evaluated its associated mechanisms. C57BL/6 mice (eight weeks old, male) and fat-1 mice (b6 background/eight weeks old, male) were divided into groups according to uremic induction, CM, and ω-3 PUFA administration. Uremia was induced via 24 h ischemia-reperfusion (IR) renal injury. One day after CM treatment, the brain tissue, kidney tissue, and blood were collected. The expression levels of glial fibrillary acidic protein (GFAP), claudin 5, CD31, laminin α4, and laminin α5 increased in ω-3 PUFA + CM-treated uremic mice and the brain of fat-1 + CM-treated uremic mice compared with those in the brains of CM-treated uremic mice. The pro-apoptotic protein expression decreased, whereas the anti-apoptotic proteins increased in ω-3 PUFA + CM-treated uremic mice and fat-1 + CM-treated uremic mice compared with CM-treated uremic mice. In addition, the brain-expression levels of p-JNK, p-P53, and p-P38 decreased in the ω-3 PUFA + CM-treated uremic mice and fat-1 + CM-treated uremic mice compared with those in wild-type uremic mice. Our results confirm that uremic toxin and CM damage the BBB and cause brain-cell death. ω-3 PUFAs play a role in BBB protection caused by CM in uremic mice.
Subject(s)
Fatty Acids, Omega-3 , Renal Insufficiency, Chronic , Reperfusion Injury , Uremia , Mice , Animals , Male , Blood-Brain Barrier/metabolism , Contrast Media , Mice, Inbred C57BL , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/metabolism , Reperfusion Injury/metabolism , Renal Insufficiency, Chronic/drug therapyABSTRACT
Dielectric materials are highly desired for pulsed power capacitors due to their ultra-fast charge-discharge rate and excellent fatigue behavior. Nevertheless, the low energy storage density caused by the low breakdown strength has been the main challenge for practical applications. Herein, we report the electric energy storage properties of (1 - x) Bi0.5(Na0.8K0.2)0.5TiO3-xBi0.2Sr0.7TiO3 (BNKT-BST; x = 0.15-0.50) relaxor ferroelectric ceramics that are enhanced via a domain engineering method. A rhombohedral-tetragonal phase, the formation of highly dynamic PNRs, and a dense microstructure are confirmed from XRD, Raman vibrational spectra, and microscopic investigations. The relative dielectric permittivity (2664 at 1 kHz) and loss factor (0.058) were gradually improved with BST (x = 0.45). The incorporation of BST into BNKT can disturb the long-range ferroelectric order, lowering the dielectric maximum temperature Tm and inducing the formation of highly dynamic polar nano-regions. In addition, the Tm shifts toward a high temperature with frequency and a diffuse phase transition, indicating relaxor ferroelectric characteristics of BNKT-BST ceramics, which is confirmed by the modified Curie-Weiss law. The rhombohedral-tetragonal phase, fine grain size, and lowered Tm with relaxor properties synergistically contribute to a high Pmax and low Pr, improving the breakdown strength with BST and resulting in a high recoverable energy density Wrec of 0.81 J/cm3 and a high energy efficiency η of 86.95% at 90 kV/cm for x = 0.45.
ABSTRACT
OBJECTIVE: We aimed to investigate current expectations and clinical adoption of artificial intelligence (AI) software among neuroradiologists in Korea. MATERIALS AND METHODS: In April 2022, a 30-item online survey was conducted by neuroradiologists from the Korean Society of Neuroradiology (KSNR) to assess current user experiences, perceptions, attitudes, and future expectations regarding AI for neuro-applications. Respondents with experience in AI software were further investigated in terms of the number and type of software used, period of use, clinical usefulness, and future scope. Results were compared between respondents with and without experience with AI software through multivariable logistic regression and mediation analyses. RESULTS: The survey was completed by 73 respondents, accounting for 21.9% (73/334) of the KSNR members; 72.6% (53/73) were familiar with AI and 58.9% (43/73) had used AI software, with approximately 86% (37/43) using 1-3 AI software programs and 51.2% (22/43) having up to one year of experience with AI software. Among AI software types, brain volumetry software was the most common (62.8% [27/43]). Although 52.1% (38/73) assumed that AI is currently useful in practice, 86.3% (63/73) expected it to be useful for clinical practice within 10 years. The main expected benefits were reducing the time spent on repetitive tasks (91.8% [67/73]) and improving reading accuracy and reducing errors (72.6% [53/73]). Those who experienced AI software were more familiar with AI (adjusted odds ratio, 7.1 [95% confidence interval, 1.81-27.81]; P = 0.005). More than half of the respondents with AI software experience (55.8% [24/43]) agreed that AI should be included in training curriculums, while almost all (95.3% [41/43]) believed that radiologists should coordinate to improve its performance. CONCLUSION: A majority of respondents experienced AI software and showed a proactive attitude toward adopting AI in clinical practice, suggesting that AI should be incorporated into training and active participation in AI development should be encouraged.
Subject(s)
Artificial Intelligence , Software , Humans , Radiologists , Surveys and Questionnaires , Internet , Republic of KoreaABSTRACT
This study aimed to investigate and optimize the quality and sensory properties of baked products with lutein-enriched marigold flower powder (MP). Lutein-enriched marigold flowers produced via hydroponic methods using LED lights were used as a functional material in sponge cakes to increase lutein content. MP particles were divided into coarse (Dv50 = 315 µm), fine (Dv50 = 119 µm), and superfine MP (Dv50 = 10 µm) fractions and added to the sponge cake after being designated to control (sponge cake prepared without MP), coarse MPS (sponge cake prepared with coarse MP), fine MPS (sponge cake prepared with fine MP), and superfine MPS (sponge cake prepared with superfine MP) groups. The sizes and surface properties of superfine MP particles were more homogeneous and smoother than the other samples. As the particle size decreased, the specific volume increased, whereas baking loss, hardness, and chewiness of the sponge cake decreased. Superfine MP and superfine MPS had the highest lutein content. The flavor of marigold and the overall acceptability of sponge cake with superfine MP were 7.90 ± 0.97 and 7.55 ± 0.76, which represents the highest values among the samples. The results of this study have shown that jet milling can contribute to improvements in texture, lutein content, and sensory qualities for baked products with MP.
ABSTRACT
Molecular clocks operate in peripheral tissues, including endocrine glands, and play important regulatory roles in this context. However, potential age-related changes in the expression rhythmicity of clock genes and the effects of these changes on the thyroid gland remain unknown. In the present study, we evaluated the expression rhythmicity of peripheral thyroid clock genes in aged mice using RNA-seq transcriptomic analysis in young (3.5-month) versus aged (20-month) mice. In addition, we determined the cellular effects of silencing of PER2, a major clock gene regulator, in human thyroid cell lines. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that differentially expressed genes (DEGs) in the thyroid glands of aged mice were involved in mitogen-activated protein kinase (MAPK) signaling, chemokine signaling, circadian entrainment, PI3K/AKT signaling, and Apelin signaling. The expression of circadian clock genes Arntl/Bmal1 was significantly downregulated in thyroid glands of aged mice, whereas the expression of genes involved in regulation of cell proliferation, migration, and tumorigenesis was upregulated. Peripheral thyroid clock genes, particularly Per mRNA and PER2 protein, were downregulated in the thyroid glands of aged mice, and circadian oscillation of these genes was declined. Knockdown of the circadian clock gene PER2 in human thyroid follicular cells induced AP-1 activity via JNK MAPK signaling activation, which increased cell proliferation. Furthermore, the aging-related loss of PER2 circadian oscillation activated the AP-1 transcription factor via the JNK MAPK pathway, which could contribute to thyroid hyperplasia, a common age-related condition.
Subject(s)
ARNTL Transcription Factors , Thyroid Neoplasms , Mice , Humans , Animals , ARNTL Transcription Factors/metabolism , CLOCK Proteins/metabolism , Period Circadian Proteins/genetics , Period Circadian Proteins/metabolism , Apelin/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Transcription Factor AP-1/metabolism , Circadian Rhythm/genetics , RNA, Messenger/genetics , Thyroid Neoplasms/genetics , Mitogen-Activated Protein Kinases/metabolism , Chemokines/metabolismABSTRACT
We herein report a facile molten-salt synthetic strategy to prepare transparent and uniform Li, Ba-doped (K,Na)NbO3 (KNN) single-crystal microcuboids (â¼80 µm). By controlling the degree of supersaturation, different growth modes were found and the single-crystal microcuboids were synthesized via island-like oriented attachment of KNN particles onto the growing surface. The distinct relaxor ferroelectric (RFE) properties were achieved in the single-crystal microcuboids, which were different from the normal ferroelectric (FE) properties found in their KNN ceramic counterparts prepared through a solid-state reaction using the same initial precursors. The RFE properties were realized by dislocation-induced nanodomain formation during oriented attachment growth of single-crystal microcuboids, which is different from the current strategies to derive the nanodomains by the local compositional inhomogeneity or the application of an electric field. The dislocations served as nucleation sites for ferroelectric domain walls and block the growth of domains. The KNN single-crystal microcuboids exhibited a higher effective piezoelectric coefficient (â¼459 pm/V) compared to that of the bulk KNN ceramic counterpart (â¼90 pm/V) and showed the broad diffuse maxima in the temperature dependence dielectric permittivity. The high maximum polarization (69.6 µC/cm2) at a relatively low electric field (30 kV/cm) was beneficial for energy storage applications. Furthermore, the KNN-based transparent, flexible pressure sensor directly monitored the mechanical motion of human activity without any external electric power. This study provides insights and synthetic strategies of single-crystal RFE microcuboids for other different perovskites, in which nanodomain structures are primarily imposed by their chemical composition.
ABSTRACT
Magneto-mechano-electric (MME) composite devices have been used in energy harvesting and magnetic field sensing applications due to their advantages including their high-performance, simple structure, and stable properties. Recently developed MME devices can convert stray magnetic fields into electric signals, thus generating an output power of over 50 mW and detecting ultra-tiny magnetic fields below pT. These inherent outstanding properties of MME devices can enable the development of not only self-powered energy harvesters for internet of thing (IoT) systems but also ultra-sensitive magnetic field sensors for diagnosis of human bio-magnetism or others. This manuscript provides a brief overview of recently reported high-performance MME devices for energy harvesting and magnetic sensing applications.
Subject(s)
Electricity , Magnetic Fields , Endrin/analogs & derivatives , Humans , Physical PhenomenaABSTRACT
Heat shock proteins (HSPs) play an essential role as molecular chaperones to prevent abnormal protein aggregation and misfolding. Moreover, they protect dopamine neurons from oxidative stress, inflammation, and apoptosis, all well-known pathomechanisms of Parkinson's disease (PD). Melatonin is a potent antioxidant that has the beneficial ability to prevent neurodegenerative diseases like PD. We aimed to explore the protective properties of melatonin in an in vitro PD model, focusing on its underlying mechanism using HSPs. A 1-methyl-4-phenylpyridimium (MPP+)-induced toxin model was established with retinoic acid (RA)-differentiated SH-SY5Y cells. Cell viability and apoptosis were measured using MTT and DAPI. Intracellular reactive oxygen species (ROS) levels were measured by the cell-permeant fluorescent probe DCFH-DA. The level of malondialdehyde and the activities of superoxide dismutase and glutathione peroxidase were assessed using ELISA kits. Apoptotic markers of Bax, Bcl2, and cleaved caspase-3, as well as HSP70 and heat shock factor-1 (HSF1), were measured by Western blot. The melatonin effect through HSP70 was tested with silencing of HSF1 in the MPP + -treated SH-SY5Y cells. Melatonin can protect against MPP + -induced neuronal toxicity by promoting anti-oxidative and anti-apoptotic properties. SH-SY5Y cells exposed to melatonin with MPP + showed increased expression of HSP70 and HSF1 compared with those exposed to MPP + alone. However, siRNA-mediated downregulation of HSF1 significantly attenuated the protective effects of melatonin in the MPP + -induced in vitro PD model. Our findings revealed the protective roles of melatonin in an in vitro PD model. Melatonin can hinder the toxic effects of MPP + on dopaminergic neuronal cells via upregulation of the HSF1/HSP70 pathway. Further experimental studies would verify the therapeutic relevance of melatonin with HSP70 and HSF1 to prevent and decelerate PD-like neurodegeneration.
Subject(s)
Melatonin , Neuroblastoma , Parkinson Disease , 1-Methyl-4-phenylpyridinium/toxicity , Apoptosis , Cell Line, Tumor , Dopaminergic Neurons , HSP70 Heat-Shock Proteins , Heat-Shock Proteins , Humans , Melatonin/pharmacology , Melatonin/therapeutic use , Parkinson Disease/drug therapyABSTRACT
BACKGROUND: Atrophy of the vocal folds and the accompanying glottic insufficiency affect the quality of life. Although growth factors have been used to treat muscle atrophy, their effectiveness is limited by their short half-life. METHODS: In total, 15 rabbits and 24 rats were used for the study. The right recurrent laryngeal nerves of all animals were transected. One month following nerve transection, PBS (PBS group), rHGF (HGF group), or a c-Met agonistic antibody (c-Met group) was injected into the paralyzed vocal folds. The larynges of the rabbits were harvested from each group for histologic examination and subjected to PCR analysis. RESULTS: Cross-sectional areas (CSAs) of thyroarytenoid muscles were evaluated. The c-Met group had increased CSAs compared to the PBS and HGF groups, but there were no significant differences compared to normal controls. The expression levels of myogenesis-related genes were evaluated three weeks after the injection. The expression levels of myosin heavy chain IIa were significantly increased in the PBS group, while the expression levels of MyoD were increased in the c-Met group. CONCLUSIONS: The c-Met agonistic antibody showed promise for promoting muscle regeneration in a vocal fold palsy model.
Subject(s)
Vocal Cord Paralysis , Vocal Cords , Animals , Laryngeal Muscles , Muscular Atrophy/metabolism , Quality of Life , Rabbits , Rats , Vocal Cord Paralysis/metabolism , Vocal Cord Paralysis/pathology , Vocal Cord Paralysis/therapy , Vocal Cords/metabolismABSTRACT
Renal fibrosis is an irreversible and progressive process that causes severe dysfunction in chronic kidney disease (CKD). The progression of CKD stages is highly associated with a gradual reduction in serum Klotho levels. We focused on Klotho protein as a key therapeutic factor against CKD. Urine-derived stem cells (UDSCs) have been identified as a novel stem cell source for kidney regeneration and CKD treatment because of their kidney tissue-specific origin. However, the relationship between UDSCs and Klotho in the kidneys is not yet known. In this study, we discovered that UDSCs were stem cells that expressed Klotho protein more strongly than other mesenchymal stem cells (MSCs). UDSCs also suppressed fibrosis by inhibiting transforming growth factor (TGF)-ß in HK-2 human renal proximal tubule cells in an in vitro model. Klotho siRNA silencing reduced the TGF-inhibiting ability of UDSCs. Here, we suggest an alternative cell source that can overcome the limitations of MSCs through the synergetic effect of the origin specificity of UDSCs and the anti-fibrotic effect of Klotho.
Subject(s)
Kidney , Klotho Proteins , Renal Insufficiency, Chronic , Stem Cells , Female , Fibrosis , Glucuronidase/metabolism , Humans , Kidney/metabolism , Kidney/pathology , Male , Regeneration , Renal Insufficiency, Chronic/metabolism , Signal Transduction , Stem Cells/metabolism , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1/metabolism , UrineABSTRACT
OBJECTIVES: To compare the dose reduction potential (DRP) of a vendor-agnostic deep learning model (DLM, ClariCT.AI) with that of a vendor-specific deep learning-based image reconstruction algorithm (DLR, TrueFidelity™). METHODS: Computed tomography (CT) images of a multi-sized image quality phantom (Mercury v4.0) were acquired under six radiation dose levels (0.48/0.97/1.93/3.87/7.74/15.47 mGy) and were reconstructed using filtered back projection (FBP) and three strength levels of the DLR (low/medium/high). The FBP images were denoised using the DLM. For all DLM and DLR images, the detectability index (d') (a task-based detection performance metric) was obtained, under various combinations of three target sizes (10/5/1 mm), five inlets (CT value difference with the background; -895/50/90/335/1000 HU), five phantom diameters (36/31/26/21/16 cm), and six radiation dose levels. Dose reduction potential (DRP) measures the dose reduction made by using DLM or DLR, while yielding d' equivalent to that of FBP at full dose. RESULTS: The DRPs of the DLM, DLR-low, DLR-medium, and DLR-high were 86% (81-88%), 60% (46-67%), 76% (60-81%), and 87% (78-92%), respectively. For 10-mm targets, the DRP of the DLM (87%) was higher than that of all DLR algorithms (58-86%). However, for smaller targets (5 mm/1 mm), the DRPs of the DLR-high (89/88%) were greater than those of the DLM (87/84%). CONCLUSION: The dose reduction potential of the vendor-agnostic DLM was shown to be comparable to that of the vendor-specific DLR at high strength and superior to those of the DLRs at medium and low strengths. KEY POINTS: ⢠DRP of the vendor-agnostic model was comparable to that of high-strength vendor-specific model and superior to those of medium- and low-strength models. ⢠Under various radiation dose levels, the deep learning model shows higher detectability indexes compared to FBP.
Subject(s)
Deep Learning , Algorithms , Drug Tapering , Humans , Image Processing, Computer-Assisted , Phantoms, Imaging , Radiation Dosage , Radiographic Image Interpretation, Computer-Assisted , Tomography, X-Ray ComputedABSTRACT
Exposure to particulate matter (PM) has been considered a potential risk factor for various neurodegenerative diseases, whereas nicotine has protective effects on Parkinson's disease (PD). However, it is still unclear whether or how PM alone and in combination with nicotine affects the pathogenesis of PD. We investigated the potential neurotoxicity of PM and the protective properties of nicotine in an in vitro PD model. A 1-methyl-4-phenylpyridimium (MPP+)-induced neurotoxicity model was established with SH-SY5Y cells. Cell viability and apoptosis were measured using MTT and TUNEL assays, respectively. Intracellular reactive oxygen species (ROS) levels were analyzed using the cell-permeant fluorescent probe DCFH-DA. We investigated mitochondrial apoptotic markers such as Bax, Bcl2, cytochrome C, and cleaved caspase-3 and analyzed their levels by Western blotting. SH-SY5Y cells exposed to PM and MPP+ exhibited significantly increased intracellular ROS and decreased cell viability with those exposed to PM alone. PM strikingly exacerbated MPP+-induced mitochondrial dysfunction, including an increase in the Bax/Bcl2 ratio and the release of cytochrome C and cleaved caspase-3. On the other hand, pretreatment of SH-SY5Y cells with nicotine reduced the MPP+-induced loss of cell viability and levels of intracellular ROS and mitochondrial apoptotic signaling proteins. However, pretreatment with nicotine did not prevent PM-induced toxicity in MPP+-treated SHSY5Y cells. PM and MPP+ synergistically increased ROS levels and mitochondrial apoptosis, which led to SH-SY5Y cell death. The protective effect of nicotine cannot rescue PM-induced synergistic neurotoxicity in the MPP+-induced PD model. Our findings verified the opposing roles of PM and nicotine in a model of PD pathogenesis. A large number of in vivo and in vitro studies would verify the roles of PM and nicotine in the future.
Subject(s)
Nicotine/pharmacology , Nicotinic Agonists/pharmacology , Parkinsonian Disorders/pathology , Particulate Matter/toxicity , 1-Methyl-4-phenylpyridinium/toxicity , Apoptosis/drug effects , Cell Death/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Humans , Neurons/drug effects , Neurons/pathology , Parkinsonian Disorders/chemically inducedABSTRACT
Polycyclic aromatic hydrocarbons (PAHs) are toxicants in particulate matter (PM). The vocal fold, part of the larynx and a key structure for voicing, is always in contact with air. In recent epidemic studies, PM was shown to cause laryngitis; however, the basic mechanism has not been evaluated. In the present study, intracellular reactive oxygen species (ROS) and proinflammatory cytokine levels were analyzed after exposing human vocal fold fibroblasts (hVFFs) to PM standard reference material (SRM 2786). Expression levels of the aryl hydrocarbon receptor (AhR) and Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) were also evaluated. PM induced ROS formation and proinflammatory cytokines via the AhR CYP1A1 pathway and caused lipid peroxidation and DNA damage. Blocking AhR or CYP1A1 production using siRNAs significantly decreased ROS production and IL-6 and IL-9 expression in PM-exposed hVFFs, thus protecting the cells against oxidative stress. These results confirm that PAHs in PM play an important role in cell damage and inflammation, confirming a basic pathophysiologic relationship between PM exposure and laryngitis.
Subject(s)
Oxidative Stress/drug effects , Particulate Matter/chemistry , Polycyclic Aromatic Hydrocarbons/toxicity , Cytochrome P-450 CYP1A1/antagonists & inhibitors , Cytochrome P-450 CYP1A1/genetics , Cytochrome P-450 CYP1A1/metabolism , Fibroblasts/cytology , Fibroblasts/metabolism , Humans , Interleukin-6/metabolism , Interleukin-8/metabolism , Polycyclic Aromatic Hydrocarbons/chemistry , RNA Interference , RNA, Small Interfering/metabolism , Reactive Oxygen Species/metabolism , Receptors, Aryl Hydrocarbon/antagonists & inhibitors , Receptors, Aryl Hydrocarbon/genetics , Receptors, Aryl Hydrocarbon/metabolism , Vocal Cords/cytologyABSTRACT
BACKGROUND: Eupatilin is an active flavon extracted from the Artemisia species and has properties such as antioxidant, anti-inflammatory, and anti-cancer. We examined the effect of eupatilin using fine particulate matter (FPM) and human bronchial epithelial cell line (BEAS-2B) to confirm the potential of eupatilin as a therapeutic agent for respiratory diseases caused by FPM. METHODS: Reactive oxygen species (ROS) levels were checked by flow cytometry to identify if FPM and eupatilin affect ROS production. Western blotting was performed to identify the mechanism of action of eupatilin in FPM-exposed BEAS-2B cells. RESULTS: When cells were exposed to FPM above 12.5 µg/mL concentration for 24 h, ROS production increased significantly compared to the control. When eupatilin was added to cells exposed to FPM, the ROS level decreased proportionally with the eupatilin dose. The phosphorylation of Akt, NF-κB p65, and p38 MAPK induced by FPM was significantly reduced by eupatilin, respectively. CONCLUSION: FPM cause respiratory disease by producing ROS in bronchial epithelial cells. Eupatilin has been shown to inhibit ROS production through altering signaling pathways. The ROS inhibiting property of eupatilin can be exploited in FPM induced respiratory disorders.
ABSTRACT
Vocal fold scarring is a major cause of dysphonia. Vocal fold fibroblasts (VFFs) and the TGF-ß signaling pathway play important roles in scar formation. Eupatilin, a chromone derivative of the Artemisia species, is a traditional folk remedy for wound healing. However, until recently, few studies investigated the therapeutic effects of eupatilin. We investigated the antifibrogenic effects of eupatilin on TGF-ß1-treated human vocal fold fibroblasts (hVFFs). The optimal concentration of eupatilin was determined by a cell viability assay. Western blotting was used to measure the expression of alpha-smooth muscle actin during myofibroblast differentiation, fibronectin (FN), collagen type I (Col I), and collagen type III (Col III) extracellular matrix proteins, and Smad2, Smad3, and p38 in the fibrotic pathway. Measurements were made before and after eupatilin treatment. Eupatilin at 100 nM was shown to be safe for use in hVFFs. TGF-ß1 induced hVFFs to proliferate and differentiate into myofibroblasts and increased Col III and FN synthesis in a time- and dose-dependent manner. Eupatilin suppressed TGF-ß1-induced hVFF proliferation and differentiation into myofibroblasts through the Smad and p38 signaling pathways. Furthermore, eupatilin inhibited TGF-ß1-induced FN, Col I, and Col III synthesis in hVFFs. Our in vitro findings show that eupatilin effectively suppressed TGF-ß1-induced fibrotic changes in hVFFs via the Smad and p38 signaling pathways. Thus, eupatilin may be considered a novel therapeutic agent for the treatment of vocal fold fibrosis.