Shifting perspectives: From "Epilepsy" to "Cerebroelectric Disorder".

BACKGROUND & OBJECTIVE: Epilepsy has long been associated with stigma and misconceptions. In response, the Korean Epilepsy Society initiated the Epilepsy Renaming project in 2008 to replace the stigmatizing term with a neutral and scientifically grounded name, "cerebroelectric disorder". This study explores the impact of changing terminology on the public discourse surrounding epilepsy. METHODS: Online news articles from distinct time periods (2001-2003, 2011-2014, 2017-2018, and 2020-2022) were analyzed using text data analysis techniques, including Latent Dirichlet Allocation topic modeling, frequency analysis, and sentiment analysis. The inclusion of data from 2017 to 2018 allowed for an examination of discourse trends independent of the COVID-19 pandemic's influence. Correlation of words in each period was visualized via network maps. Migraine was set as control term to highlight changes in perception devoid of significant stigma intervention efforts. RESULTS: The analysis revealed a significant shift in terminology preference, with cerebroelectric disorder gradually replacing epilepsy in news articles. The discourse surrounding epilepsy evolved over time from focusing on healthcare and economic aspects to patient-centered discussions, emphasizing the daily lives of individuals with epilepsy. This shift towards more empathetic and less stigmatized language was contrasted against the discourse on migraine, highlighting the specific impact of the terminological change on epilepsy's perception. CONCLUSION: The adoption of the neutral term "cerebroelectric disorder" in South Korea has influenced the discourse surrounding epilepsy, leading to more patient-centered discussions and a reduction in stigma. This study highlights the importance of terminology in shaping public perceptions of diseases and suggests that changing terminology can positively impact the understanding and destigmatization of epilepsy.

Chemical Profile Determination and Quantitative Analysis of Components in Oryeong-san Using UHPLC-Q-Orbitrap-MS and UPLC-TQ-MS/MS.

In this study, a method to both qualitatively and quantitively analyze the components of Oryeong-san (ORS), which is composed of five herbal medicines (Alisma orientale Juzepzuk, Polyporus umbellatus Fries, Atractylodes japonica Koidzumi, Poria cocos Wolf, and Cinnamomum cassia Presl) and is prescribed in traditional Oriental medicine practices, was established for the first time. First, ORS components were profiled using ultra-high-performance liquid chromatography/quadrupole Orbitrap mass spectrometry, and 19 compounds were clearly identified via comparison against reference standard compounds. Subsequently, a quantitative method based on ultra-high-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry was established to simultaneously measure the identified compounds. Nineteen compounds were accurately quantified using the multiple-reaction-monitoring mode and used to analyze the sample; we confirmed that coumarin was the most abundant compound. The method was validated, achieving good linearity (R2 ≤ 0.9991), recovery (RSD, 0.11-3.15%), and precision (RSD, 0.35-9.44%). The results suggest that this method offers a strategy for accurately and effectively determining the components of ORS, and it can be used for quality assessment and management.

Qualitative Profiling and Quantitative Analysis of Major Constituents in Jinmu-tang by UHPLC-Q-Orbitrap-MS and UPLC-TQ-MS/MS.

Jinmu-tang (JMT) is a traditional herbal medicine consisting of five herbal medicines: Poria cocos Wolf, Paeonia lactiflora Pallas, Zingiber officinale Roscoe, Atractylodes japonica Koidzumi, and Aconitum carmichaeli Debeaux. In this study, the JMT components were profiled using UHPLC-Q-Orbitrap-MS, and 23 compounds were identified and characterized. In addition, UPLC-TQ-MS/MS analysis was performed in the positive and negative ion modes of an electrospray ionization source for the simultaneous quantification of the identified compounds. The multiple reaction monitoring (MRM) method was established to increase the sensitivity of the quantitative analysis, and the method was verified through linearity, recovery, and precision. All analytes showed good linearity (R2 ≤ 0.9990). Moreover, the recovery and the relative standard deviation of precision were 86.19-114.62% and 0.20-8.00%, respectively. Using the established MRM analysis method, paeoniflorin was found to be the most abundant compound in JMT. In conclusion, these results provide information on the constituents of JMT and can be applied to quality control and evaluation.

Blue Phosphorescence with High Quantum Efficiency Engaging the Trifluoromethylsulfonyl Group to Iridium Phenylpyridine Complexes.

Incorporation of an electron-withdrawing -SO2CF3 substituent to cyclometalating C^N-phenylpyridine (ppy) ligand resulted in an expected blue-shifted phosphorescence in the corresponding homoleptic Ir(ppySCF3)3 complex, showing the emission of λem = 464 nm at 300 K. One of its heteroleptic derivatives, modified by a pyrazolyl borate LX ligand, Ir(ppySCF3)2(bor), exhibited further blue-shifted phosphorescence of λem = 460 nm at 300 K. Cyclic voltammograms (CVs) and density-functional theory (DFT) calculations supported the efficacy of the electron-withdrawing capability of the SO2CF3 substituent lowering HOMO energy and obtained widened bandgaps and resumed blue emissions for all of the iridium complexes studied. The homoleptic complexes of both substituents, Ir(ppySCF3)3 and Ir(ppySF)3, reached the higher quantum yields (ΦPL) of (0.89 and 0.72), respectively. Similarly, emission quantum yields (ΦPL) of the heteroleptic derivatives were reported to be (0.75, 0.83, and 0.87) for Ir(ppySCF3)2(acac), Ir(ppySCF3)2(bor), and Ir(ppySCF3)2(pic), respectively. Emission kinetics support the enhanced quantum efficiency when kr and knr values are compared between Ir(ppySCF3)3 and Ir(ppySF)3, and both values favorably contribute to attaining a higher quantum efficiency for Ir(ppySCF3)3. Among solution-processed multilayered devices having an ITO/PEDOT:PSS/TCTA:Ir dopant (10:1, w/w)/TmPyPB/Liq/Al structure, a heteroleptic dopant, Ir(ppySCF3)2(bor), exhibited better device performance, reporting an external quantum efficiency (EQE) of 1.14%, current efficiency (CE) of 2.31 cd A-1, and power efficiency (PE) of 1.21 lm W-1, together with blue chromaticity of CIEx,y = (0.16, 0.32).

Effect of Silyl Ether-functinoalized Dimethoxydimethylsilane on Electrochemical Performance of a Ni-rich NCM Cathode.

Dimethoxydimethylsilane (DODSi) is used as an interface stabilizing additive through a selective HF scavenging reaction for layered Ni-rich oxide cathodes. Ex situ NMR analyses demonstrated that DODSi effectively removes HF from the electrolyte based on the matched chemical reactivity of Si with F- and O with H+ . The cells employing DODSi exhibit higher specific capacity with retention than those cycled with a DODSi-free electrolyte even under in situ HF generating conditions. Scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and inductively coupled plasma-mass spectroscopy (ICP-MS) analyses indicate that DODSi effectively protects the Ni-rich oxide cathodes against HF corrosion, resulting in improved surface stability of Ni-rich cathodes.

The Korean herbal medicine, Do In Seung Gi-Tang, attenuates atherosclerosis via AMPK in high-fat diet-induced ApoE(-/-) mice.

BACKGROUND: Do In Seung Gi-Tang (DISGT) is an herbal mixture of traditional Korean medicine that is composed of Rheum undulatum Linne, Prunus Persica (L.) Batsch, Conyza canadensis L., Cinnamomum Cassia Presl, and Glycytthiza uralensis Fischer (8: 6: 4: 4: 4 ratio). We investigated the effect of DISGT on vascular inflammation and lipid accumulation in apolipoprotein E-deficient (ApoE(-/-)) mice. METHODS: ApoE(-/-) mice that were fed a high-fat diet (HFD) were treated with DISGT (300 mg/kg/day) or statin (10 mg/kg/day) for 16 weeks. Serum lipid levels were analyzed. Oil Red O staining was used to evaluate atherosclerotic lesions and lipid accumulation in the aorta and liver, respectively. The expression of adhesion molecules (intercellular adhesion molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1], and E-selectin), fatty acid synthase (FAS), adenosine monophosphate-activated protein kinase (AMPK), and acetyl-coA carboxylase (ACC) in the aorta or liver tissues was measured by western blot analysis. Lipid synthesis and inflammatory responses were assessed by immunohistochemistry and hematoxylin & eosin staining, respectively. RESULTS: Treatment of HFD-fed mice with DISGT significantly lowered body weight, liver weight, and the levels of lipids, including total cholesterol, low-density lipoprotein-cholesterol, and triglycerides. Glucose levels were also lowered. In the aorta, DISGT attenuated atherosclerotic lesions and reduced the expression of ICAM-1, VCAM-1, and E-selectin. Moreover, DISGT decreased lipid accumulation, inflammatory responses, and FAS levels, and it activated AMPK and reduced ACC expression in liver tissues. CONCLUSIONS: The beneficial, anti-lipolytic, and anti-inflammatory effects of DISGT were mediated by the AMPK pathway. As a result, the expression of inflammatory factors was reduced. Our data provide evidence that DISGT may have strong therapeutic potential in treating vascular diseases, such as atherosclerosis.

Reynoutria japonica consisted of emodin-8-ß-D-glucoside ameliorates Dermatophagoides farinae extract-induced atopic dermatitis-like skin inflammation in mice by inhibiting JAK/STAT signaling.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by skin barrier dysfunction and chronic inflammatory responses. Reynoutria japonica, known as Huzhang in traditional Chinese Medicine, can enhance blood circulation to eliminate wind pathogens and terminate coughing. Despite pharmacological evidence supporting the efficacy of R. japonica in suppressing edema-induced skin inflammation or connective tissue diseases, its pharmaceutical potential for treating AD-like skin inflammation remains unexplored. This study investigated the possible effects of R. japonica ethanol extract (RJE) on Dermatophagoides farinae extract (DfE)-induced AD-like skin inflammation in NC/Nga mice. To elucidate the underlying mechanisms by which RJE inhibits skin inflammation, we examined the effect of RJE on IFN-γ/TNF-α-induced signal transducer and activator of transcription (STAT) signaling in human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs). Our findings revealed that RJE mitigates DfE-induced AD-like symptoms and skin barrier disruptions in mouse skin lesions. Moreover, RJE attenuated DfE-induced mast cell infiltration and serum levels of inflammatory cytokines (IL-1α, IL-1ß, IL-6, IL-23, IFN-γ, TNF-α, and GM-CSF). RJE also inhibited IFN-γ/TNF-α-induced chemokine levels and STAT3 phosphorylation in HEKs and HDFs. Virtual binding analysis of the RJE components suggested that emodin-8-ß-D-glucoside binds to Janus kinase (JAK) 1/2, thereby suppressing STAT signaling, which was confirmed by Western blot analysis. In conclusion, our results suggest that RJE may alleviate DfE-induced skin barrier dysfunction by inhibiting JAK/STAT signaling and the proinflammatory immune response through the suppression of inflammatory mediators in AD-like skin disease. These findings suggest that RJE has potential as an effective therapy for AD management.

Higher mortality and longer length of stay in hospitalized patients with newly diagnosed diabetes.

AIMS: We investigated the association between diabetes status at admission and in-hospital outcomes in all hospitalized patients, regardless of the reason for admission. METHODS: All individuals aged 20 years or older who were admitted to Yongin Severance Hospital between March 2020 and February 2022 were included in study. Subjects were categorized into three groups: non-DM, known DM, and newly diagnosed DM, based on medical history, anti-diabetic medications use, and laboratory test. Hospitalization-related outcomes, including in-hospital mortality and length of hospital stay, were compared between groups. RESULTS: 33,166 participants were enrolled. At hospitalization, 6,572 (19.8 %) subjects were classified as known DM, and another 2,634 (7.9 %) subjects were classified as newly diagnosed DM. In-hospital mortality was highest in newly diagnosed DM (HR 1.89, 95% CI 1.58-2.26, p < 0.001) followed by known DM (HR 1.41, 95% CI 1.18-1.69, p < 0.001) compared to non-DM. Length of hospital stay was significantly longer in newly diagnosed DM (median [IQR] 9.0 [5.0-18.0],days) than known DM (median [IQR] 5.0 [3.0-10.0],days)(p < 0.001) and non-DM (median [IQR] 4.0 [2.0-7.0],days). After adjusting for multiple covariates, newly diagnosed diabetes was independently associated with increased in-hospital mortality (p < 0.001). CONCLUSIONS: Diabetes status at admission was closely linked to hospitalization-related outcomes. Notably, individuals with newly diagnosed diabetes demonstrated a higher risk of in-hospital mortality and a prolonged length of hospital stay.

Inhibitory effect of Sanguisorba hakusanensis Makino ethanol extract on atopic dermatitis-like responses in NC/Nga mice and human keratinocytes.

Atopic dermatitis (AD) is an allergic, inflammatory skin disease caused by immune dysregulation. In this study, we investigated anti-atopic and anti-inflammatory activities of Sanguisorba hakusanensis ethanol extract (SHE) both in vivo using NC/Nga mice and in vitro using human HaCaT keratinocytes. Oral administration of SHE suppressed several atopic symptoms associated with house dust mites (induced with Dermatophagoides farinae extract) in NC/Nga mice and decreased serum levels of inflammatory mediators such as immunoglobulin E, histamine, and inflammatory chemokines. Additionally, SHE treatment reduced the infiltration of immune cells such as mast cells and macrophages in AD skin lesions. In vitro, interferon-γ- and tumor necrosis factor-α-stimulated HaCaT cells exhibited increased expression of T helper 1 and 2 chemokines; their expression was inhibited by SHE treatment. The anti-inflammatory effects of SHE treatment involved blocking of the mitogen-activated protein kinase and signal transducer and activator of transcription 1 signaling pathways. In conclusion, SHE exerts potent anti-atopic and anti-inflammatory effects and should be considered for the clinical treatment of AD.

Topical Administration of Gardenia jasminoides Extract Regulates Th2 Immunity in OVA-Induced Mice.

A key feature of an allergic immune response is a T helper type 2 (Th2)-mediated response with production of allergen-specific IgE antibodies. Gardenia jasminoides extract with the crocin removed (GJExCR) has been shown to inhibit IgE-mediated allergic disease. To evaluate the efficacy and mechanism-of-action of this inhibition, GJExCR was used in an ovalbumin (OVA)-induced allergy model in BALB/C mice. Sensitization of BALB/C mice with OVA and aluminum hydroxide was performed on days 1 and 14 by intraperitoneal injection, followed by OVA challenge to the dorsal skin for 2 weeks before removal. Seven days post-challenge, mice were treated with GJExCR topically every day for 11 days. Enzyme-linked immunosorbent assay, flow cytometry analysis, real-time PCR, and western blot were performed to determine IgE and Th2 cytokine levels. Following OVA challenge, Th2 cytokine expression and both total and OVA-specific serum IgE levels increased, of which OVA-specific IgE and Th2 cytokine levels decreased after GJExCR treatment. Flow cytometry analysis revealed that GJExCR treatment decreased CD4+ and CD8+ T cell populations in the spleen and lymph nodes. In addition, treatment with GJExCR downregulated signal transducer and activator of transcription 1 (STAT1) activation and Th2 cytokine levels as compared to control. GJExCR containing geniposide downregulated STAT1 activation in HaCaT cells. These findings demonstrate that GJExCR exerts its anti-allergy effect via inhibition of STAT1 activation, thus regulating the immune response via modulation of Th2 cytokine release and IgE levels. Therefore, we propose GJExCR as a potential treatment for allergic hypersensitivity reactions.

Deep-Learning-Based Detection of Vertebral Fracture and Osteoporosis Using Lateral Spine X-Ray Radiography.

Osteoporosis and vertebral fractures (VFs) remain underdiagnosed. The addition of deep learning methods to lateral spine radiography (a simple, widely available, low-cost test) can potentially solve this problem. In this study, we develop deep learning scores to detect osteoporosis and VF based on lateral spine radiography and investigate whether their use can improve referral of high-risk individuals to bone-density testing. The derivation cohort consisted of patients aged 50 years or older who underwent lateral spine radiography in Severance Hospital, Korea, from January 2007 to December 2018, providing a total of 26,299 lateral spine plain X-rays for 9276 patients (VF prevalence, 18.6%; osteoporosis prevalence, 40.3%). Two individual deep convolutional neural network scores to detect prevalent VF (VERTE-X pVF score) and osteoporosis (VERTE-X osteo score) were tested on an internal test set (20% hold-out set) and external test set (another hospital cohort [Yongin], 395 patients). VERTE-X pVF, osteo scores, and clinical models to detect prevalent VF or osteoporosis were compared in terms of the areas under the receiver-operating-characteristics curves (AUROCs). Net reclassification improvement (NRI) was calculated when using deep-learning scores to supplement clinical indications for classification of high-risk individuals to dual-energy X-ray absorptiometry (DXA) testing. VERTE-X pVF and osteo scores outperformed clinical models in both the internal (AUROC: VF, 0.93 versus 0.78; osteoporosis, 0.85 versus 0.79) and external (VF, 0.92 versus 0.79; osteoporosis, 0.83 versus 0.65; p < 0.01 for all) test sets. VERTE-X pVF and osteo scores improved the reclassification of individuals with osteoporosis to the DXA testing group when applied together with the clinical indications for DXA testing in both the internal (NRI 0.10) and external (NRI 0.14, p < 0.001 for all) test sets. The proposed method could detect prevalent VFs and osteoporosis, and it improved referral of individuals at high risk of fracture to DXA testing more than clinical indications alone. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Agrobacterium tumefaciens-Mediated Transformation of the Aquatic Fungus Phialemonium inflatum FBCC-F1546.

Phialemonium inflatum is a useful fungus known for its ability to mineralise lignin during primary metabolism and decompose polycyclic aromatic hydrocarbons (PAHs). However, no functional genetic analysis techniques have been developed yet for this fungus, specifically in terms of transformation. In this study, we applied an Agrobacterium tumefaciens-mediated transformation (ATMT) system to P. inflatum for a functional gene analysis. We generated 3689 transformants using the binary vector pSK1044, which carried either the hygromycin B phosphotransferase (hph) gene or the enhanced green fluorescent protein (eGFP) gene to label the transformants. A Southern blot analysis showed that the probability of a single copy of T-DNA insertion was approximately 50% when the co-cultivation of fungal spores and Agrobacterium tumefaciens cells was performed at 24-36 h, whereas at 48 h, it was approximately 35.5%. Therefore, when performing gene knockout using the ATMT system, the co-cultivation time was reduced to ≤36 h. The resulting transformants were mitotically stable, and a PCR analysis confirmed the genes' integration into the transformant genome. Additionally, hph and eGFP gene expressions were confirmed via PCR amplification and fluorescence microscopy. This optimised transformation system will enable functional gene analyses to study genes of interest in P. inflatum.

Gardenia jasminoides extract ameliorates DfE-induced atopic dermatitis in mice through restoration of barrier function and T-helper 2-mediated immune response.

Atopic dermatitis (AD) leads to skin barrier abnormalities and immune dysfunction. As the topical steroids commonly used to treat AD have side effects from long-term use, research into safer treatments for AD is greatly needed. The medicinal herb Gardenia jasminoides improves AD symptoms via skin barrier activation and T helper 2-mediated immune response regulation. Crocin, a bioactive component within the extract, is dispensible for its restorative effects. As such, this work explored the effects of Gardenia jasminoides extract without crocin (GjexCr) on AD symptoms in a DfE-induced AD model in 6-week-old male NC/Nga mice (25.0 ± 0.25 g, n = 10 each, 6 groups). Using histological and behavioral assays, the effects of GjexCr on dermatitis scores, scratching behavior, skin barrier activation, and serum levels of IgE, chemokines, and cytokines were analyzed. In addition, the major components from the GjexCr extract were analyzed by high-performance liquid chromatography and validated in the AD model. GjexCr reduced ear thickness due to hyperkeratosis, dermal thickening, and scratching behavior and restored dermatitis scores in AD-induced mice. GjexCr administration also decreased inflammation and mast cell infiltration, as well as modulated skin barrier recovery by upregulating the production of epidermal proteins. Moreover, GjexCr administration attenuated imbalanced immune responses. Furthermore, geniposide, the main component of GjexCr, improved AD symptoms in DfE-treated NC/Nga mice. Thus, GjexCr could be a suitable treatment for protecting the skin barrier in AD-like skin lesions and a potential therapy for AD.

Risk of Carotid Atherosclerosis in Subjects with Prediabetes Overlapping Metabolic Syndrome.

Background: While the number of individuals with prediabetes and metabolic syndrome (MetS) is increasing, only a few studies have reported differences in cardiovascular risk according to the presence or absence of MetS in individuals with prediabetes. Here, we examined differences in carotid intima-media thickness (CIMT) and carotid plaques in individuals with prediabetes with or without MetS among subjects who visited a single center in Seoul (Huh Diabetes Center). Methods: A total of 328 participants aged ≥20 years, including the group with normoglycemia, were enrolled in the analysis, of which 273 had prediabetes. Individuals with prediabetes were defined as those who met one or more of the following two criteria: fasting plasma glucose of 100-125 mg/dL and/or HbA1c level of 5.7%-6.4%. Carotid atherosclerosis was determined by mean and maximal CIMT and by the presence of carotid plaques. Results: Eighty-nine subjects (32.6% of prediabetes group) were categorized as having MetS. Those with MetS had significantly higher mean CIMT and maximal CIMT than those without (P < 0.05). Moreover, the group with MetS had a significantly higher prevalence of carotid plaques than the group without MetS [odds ratio (OR): 2.45, 95% confidence interval (CI): 1.43-4.19; P = 0.001]. After adjusting for age, sex, body mass index, and low-density lipoprotein cholesterol, individuals with MetS still had greater mean and maximal CIMT than individuals without MetS (P < 0.05), and the presence of MetS was significantly associated with a higher risk of carotid plaques (OR: 2.55, 95% CI: 1.06-6.15; P = 0.037). Conclusion: These results suggest that MetS is independently associated with increased CIMT and the presence of carotid plaques in prediabetes. Our study indicates that the risk of cardiovascular disease (CVD) is high in prediabetic individuals with MetS, and that more attention is needed on the risk of CVD in these individuals.

Association Between Low Serum Phosphate Level and Risk of Falls in Hospitalized Patients Over 50 Years of Age: A Retrospective Observational Cohort Study.

Purpose: Falls are the leading cause of injury among hospitalized patients, particularly among older patients. We investigated the association between serum phosphate (s-phosphate) levels and the risk of in-hospital falls. Patients and Methods: This retrospective observational cohort study included all patients aged over 50 years who were admitted to Yongin Severance Hospital in South Korea between January 2018 and March 2021. Demographic, anthropometric, and biochemical parameters were recorded on admission. S-phosphate levels were classified into three groups: below normal (<2.8 mg/dL), normal (2.8-4.4 mg/dL), and above normal (≥4.5 mg/dL). The normal group was further stratified into tertiles (2.8-3.2, 3.3-3.7, and 3.8-4.4 mg/dL). The incidence of in-hospital falls was compared between the five groups. Logistic regression analyses were performed to assess the association between s-phosphate levels and the incidence of falls during the hospital stay, with clinical factors included as covariates in the multivariable models. Results: A total of 15,485 patients (female: 52.1%) with a median age of 70.0 years (interquartile range: 60.0-79.0 years) were included in the analysis, of whom 295 (1.9%) experienced a fall during the hospital stay. The incidence of falls was significantly higher among patients with lower s-phosphate levels, and this relationship also applied among patients with s-phosphate levels within the normal range as well. The association between lower s-phosphate levels and increased risk of falls remained significant in the adjusted analyses. Conclusion: A lower s-phosphate level on admission was independently associated with an increased risk of in-hospital falls. Further studies are needed to determine whether the s-phosphate level on admission could improve prediction of the risk of in-hospital falls.

Spatholobus suberectus Dunn Water Extract Ameliorates Atopic Dermatitis-Like Symptoms by Suppressing Proinflammatory Chemokine Production In Vivo and In Vitro.

S. patholobus suberectus Dunn, a traditional Chinese herbal medicine, has various pharmacological activities, such as anti-inflammatory properties. However, to the best of our knowledge, its therapeutic effect on atopic dermatitis (AD) has not been investigated. In this study, we explored the effect of S. suberectus Dunn water extract (SSWex) on AD in vivo and in vitro. In Dermatophagoides farina extract (DfE)-treated NC/Nga mice, the oral administration of SSWex alleviated AD-like symptoms, such as ear thickness, dermatitis score, epidermal thickness, immune cell infiltration, and levels of AD-related serum parameters (immunoglobulin E, histamine, and proinflammatory chemokines). In HaCaT cells, the production of proinflammatory chemokines induced by interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) was inhibited by SSWex pretreatment. SSWex treatment inhibited the phosphorylation of mitogen-activated protein kinase and activation and translocation of transcriptional factors, such as signal transducer and activator of transcription 1 and nuclear factor kappa B in IFN-γ/TNF-α-stimulated HaCaT cells. These results indicate that SSWex may be developed as an efficient therapeutic agent for AD.

Experimental and Computational Approaches to Sulfonated Poly(arylene ether sulfone) Synthesis Using Different Halogen Atoms at the Reactive Site.

Engineering thermoplastics, such as poly(arylene ether sulfone), are more often synthesized using F-containing monomers rather than Cl-containing monomers because the F atom is considered more electronegative than Cl, leading to a better condensation polymerization reaction. In this study, the reaction's spontaneity improved when Cl atoms were used compared to the case using F atoms. Specifically, sulfonated poly(arylene ether sulfone) was synthesized by reacting 4,4'-dihydroxybiphenyl with two types of biphenyl sulfone monomers containing Cl and F atoms. No significant difference was observed in the structural, elemental, and chemical properties of the two copolymers based on nuclear magnetic resonance spectroscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, X-ray diffraction, transmission electron microscopy, and electrochemical impedance spectroscopy. However, the solution viscosity and mechanical strength of the copolymer synthesized with the Cl-terminal monomers were slightly higher than those of the copolymer synthesized with the F-terminal monomers due to higher reaction spontaneity. The first-principle study was employed to elucidate the underlying mechanisms of these reactions.

Terminalia chebula Retz. extract ameliorates the symptoms of atopic dermatitis by regulating anti-inflammatory factors in vivo and suppressing STAT1/3 and NF-ĸB signaling in vitro.

BACKGROUND: Terminalia chebula (TC) is a traditional medicinal plant used for treating various diseases in humans. However, pharmacological mechanisms underlying the effects of TC in atopic treatment remain unelucidated. HYPOTHESIS/PURPOSE: We investigated the therapeutic effects of TC extract in a mouse model of atopic dermatitis (AD) in vivo and the anti-inflammatory mechanism in vitro. STUDY DESIGN/METHODS: For the in vivo study, AD was induced by Dermatophagoides farinae extract (Dfe) in NC/Nga mice. After 14 days of oral administration, the effects of TC concentrations of 30, 100, and 300 mg/kg were analyzed by assessing morphological changes visually; measuring serum levels of inflammatory chemokines/cytokines, IgE, histamine, MDC, TARC, RANTES, and TSLP using ELISA kits; and counting infiltrated mast cells. For in vitro analyses, we used IFNγ/TNF-α-stimulated human keratinocyte cell lines to study the mechanism of action. The production of chemokines/cytokines in the IFNγ/TNF-α-stimulated HaCaT cells was measured using ELISA and a bead array kit. The signaling pathways were analyzed by western blotting and the expression of the transcriptional factors using RT-PCR and luciferase assay. RESULTS: Administration of TC significantly alleviated AD-like symptoms in vivo and decreased the ear thickness, dermatitis score, keratinization, and mast cell infiltration. It also resulted in decreased serum levels of IgE, histamine, and inflammation-related mediators MDC, TARC, RANTES, and TSLP compared with those in the Dfe treatment group. Moreover, TC downregulated the expression of the inflammatory chemokines RANTES and MDC in IFNγ/TNF-α-stimulated HaCaT cells. TC inhibited phosphorylated STAT1/3 and NK-κB subunits and nuclear translocation of NF-κB. It also suppressed the transcription of IFNγ, IL-6, IL-8 and MCP-1 in the IFNγ/TNF-α-stimulated HaCaT cells. TC and its constituents, chebulic acid, gallic acid, corlagin, chebulanin, chbulagic acid, ellagic acid, and chebulinic acid, strongly inhibited the nuclear translocation of NF-κB, STAT1, and STAT3 and decreased the expression of inflammatory cytokines at the mRNA level. CONCLUSIONS: Overall, TC extract alleviated AD-like symptoms by regulating anti-inflammatory factors in vivo and suppressing STAT1/3 and NF-κB signaling in vitro. In addition, our results show the in vivo effect of partial improvements in AD, as well as the in vitro effect on inflammatory factors by the constituents of TC. This finding provides that TC extract and its components could be potential therapeutic drugs for AD.

Ethanol extract of Veronica persica ameliorates house dust mite-induced asthmatic inflammation by inhibiting STAT-3 and STAT-6 activation.

Veronica persica is a flowering plant belonging to the family Scrophulariaceae. Here, we aimed to evaluate the pharmacological activity of the ethanol extract of Veronica persica (EEVP) in an airway inflammation model. We examined airway responsiveness to aerosolized methacholine, serum immunoglobulin (Ig)E levels, and total cell numbers in the lung and bronchoalveolar lavage fluid (BALF). Histological analysis of the lung tissue was performed using hematoxylin-eosin, Masson trichrome, or periodic acid-Schiff staining. Fluorescence-activated cell sorting analysis in the lung and BALF was applied to clarify the changes in immune cell types. Enzyme-linked immunosorbent assay and quantitative real-time polymerase chain reaction were applied to investigate cytokine levels and gene expression related to airway inflammation. STAT-3/6 phosphorylation was examined in primary bronchial/tracheal epithelial cells using western blot analysis. EEVP significantly suppressed total IgE levels and methacholine-induced increase of Penh value in the HDM-challenged mouse model. EEVP also attenuated the severity of airway remodeling in lung tissues and decreased eosinophil and neutrophil infiltration in the lungs and BALF. EEVP significantly reduced the production of cytokines in BAL and splenocyte culture medium, and the expression of mRNAs related to airway inflammation in the lung tissue. EEVP suppressed IL-4/13-induced STAT-3/6 phosphorylation in the epithelial cells. We showed for the first time that EEVP effectively inhibits eosinophilic airway inflammation by suppressing the expression of inflammatory factors for T cell activation and polarization, and inhibits MCP-1 production of bronchial/tracheal epithelial cells by suppressing STAT-3/6 activation. EEVP may be a potential pharmacological agent to prevent inflammatory airway diseases.

Alpinia officinarum water extract inhibits the atopic dermatitis-like responses in NC/Nga mice by regulation of inflammatory chemokine production.

Alpinia officinarum (AO) has been traditionally used in Asia as an herbal medicine to treat inflammatory and internal diseases. However, the therapeutic effect of AO on atopic dermatitis (AD) is unclear. Therefore, we examined whether Alpinia officinarum water extract (AOWex) affects AD in vivo and in vitro. Oral administration of AOWex to NC/Nga mice with Dermatophagoies farina extract (DfE)-induced AD-like symptoms significantly reduced the severity of clinical dermatitis, epidermal thickness, and mast cell infiltration into the skin and ear tissue. Decreased total serum IgE, macrophage-derived chemokine (MDC), and regulated on activation, normal T-cell expressed and secreted (RANTES) levels were observed in DfE-induced NC/Nga mice in the AOWex-treated group. These effects were confirmed in vitro using HaCaT cells. Treatment with AOWex inhibited the expression of proinflammatory chemokines such as MDC, RANTES, IP-10 and I-TAC in interferon-γ and tumor necrosis factor-α-stimulated HaCaT cells. The anti-inflammatory effects of AOWex were due to its inhibitory action on MAPK phosphorylation (ERK and JNK), NF-κB, and STAT1. Furthermore, galangin, protocatechuic acid, and epicatechin from AOWex were identified as candidate anti-AD compounds. These results suggest that AOWex exerts therapeutic effects against AD by alleviating AD-like skin lesions, suppressing inflammatory mediators, and inhibiting major signaling molecules.