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Background: Rheumatoid arthritis (RA) is a chronic inflammatory disorder primarily targeting joints, significantly impacting patients' quality of life. The introduction of tumor necrosis factor-alpha (TNF-α) inhibitors has markedly improved RA management by reducing inflammation. However, these medications are associated with adverse skin reactions, which can vary greatly among patients due to genetic differences. Objectives: This study aimed to identify risk factors associated with skin adverse events by TNF-α in RA patients. Methods: A cohort study was conducted, encompassing patients with RA who were prescribed TNF-α inhibitors. This study utilized machine learning algorithms to analyze genetic data and identify markers associated with skin-related adverse events. Various machine learning algorithms were employed to predict skin and subcutaneous tissue-related outcomes, leading to the development of a risk-scoring system. Multivariable logistic regression analysis identified independent risk factors for skin and subcutaneous tissue-related complications. Results: After adjusting for covariates, individuals with the TT genotype of rs12551103, A allele carriers of rs13265933, and C allele carriers of rs73210737 exhibited approximately 20-, 14-, and 10-fold higher incidences of skin adverse events, respectively, compared to those with the C allele, GG genotype, and TT genotype. The machine learning algorithms used for risk prediction showed excellent performance. The risk of skin adverse events among patients receiving TNF-α inhibitors varied based on the risk score: 0 points, 0.6%; 2 points, 3.6%; 3 points, 8.5%; 4 points, 18.9%; 5 points, 36.7%; 6 points, 59.2%; 8 points, 90.0%; 9 points, 95.7%; and 10 points, 98.2%. Conclusions: These findings, emerging from this preliminary study, lay the groundwork for personalized intervention strategies to prevent TNF-α inhibitor-associated skin adverse events. This approach has the potential to improve patient outcomes by minimizing the risk of adverse effects while optimizing therapeutic efficacy. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease influenced by a complex interplay of genetic and environmental factors. The activation of the JAK-STAT pathway increases the expression of inflammatory cytokines such as IL-4 and IL-13, further deteriorating AD. Therefore, for the treatment of AD, the JAK-STAT pathway is emerging as a significant target, alongside inflammatory cytokines. This study investigates the potential therapeutic effects of a novel herbal complex, LK5, composed of Scutellaria baicalensis, Liriope platyphylla, Sophora flavescens, Dictammus dasycarpus, and Phellodendron schneider, known for their anti-inflammatory and immune-modulating properties. We examined the anti-inflammatory and anti-AD effects of the LK5 herbal complex in HaCaT cells stimulated by LPS and IL-4/IL-13, as well as in a mouse model of AD induced by DNCB. In HaCaT cells stimulated with LPS or IL-4/IL-13, the LK5 herbal complex demonstrated anti-inflammatory effects by inhibiting the expression of inflammatory cytokines including TNF-α, IL-6, and IL-1β, and downregulating the phosphorylation of STAT proteins. In a murine AD-like model induced by DNCB, administration of the LK5 herbal complex significantly ameliorated clinical symptoms, including dermatitis, ear thickness, and TEWL. Histological analysis revealed a reduction in epidermal thickness and mast cell infiltration. The LK5 herbal complex also inhibited pruritus induced by compound 48/80. Furthermore, the LK5 herbal complex treatment significantly decreased the levels of inflammatory cytokines such as TSLP, IL-6, and IgE in plasma and ear tissue of AD-induced mice. These findings suggest that the LK5 herbal complex may modulate the immune response and alleviate AD symptoms by inhibiting STAT pathways. [ABSTRACT FROM AUTHOR]

Simple Summary: Bluetongue (BT) is an economically significant disease in ruminants, transmitted worldwide by Culicoides midges, with the causative agent being the bluetongue virus (BTV). Traditionally prevalent in tropical regions, its geographic range is expanding due to climate change. Despite its global impact, research on the BTV in the Republic of Korea (ROK) is scarce. In this study, we aimed to assess BTV seroprevalence and conduct genetic analyses on isolates from South Korea. Out of 5824 cattle samples, 194 (3.33%) showed BTV antibodies, and 2 out of 1095 (0.18%) goat samples were positive. BTV RNA analyses of 422 high-risk area cattle samples revealed 51 (12.1%) positive cases. The virus was successfully isolated from one sample, identified as serotype 3 based on segment 2 analysis. This study presents the first full-genome sequence of a South Korean BTV serotype 3 isolate, serving as a global reference. These data aid in understanding phylogenetic relationships among BTV strains and recognizing reassortment events, enhancing our knowledge of this developing virus. The bluetongue virus (BTV) is a significant animal pathogen with economic implications in the ruminant industry. Despite global reports on BTV detection and epidemiologic investigations, limited studies have focused on the virus in the ROK. In this study, BTV epidemiological research was conducted on blood samples from cattle and goat farms across nine regions during 2013–2014. The results showed that 3.33% of bovine blood samples (194/5824) and 0.19% of goat blood samples (2/1075) tested positive for BTV antibodies using ELISA. In Jeju-do, BTV RNA amplification occurred in 51 of 422 samples (12.1%) using real-time reverse transcription (RT-qPCR). The isolation of one sample revealed it as serotype 3, as indicated by the sequence of segments 2 (Seg-2) and 6 (Seg-6), associated with the eastern BTV topotype. However, based on Seg-1, -3, -4, -5, -7, -8, -9, and -10 analyses, the BTV-3/JJBB35 strain is more closely related to distinct BTV strains. These findings imply BTV circulation and that the Korean-isolated BTV might originate from Asian BTV strains due to multiple reassortment events. This study provides foundational data for ongoing BTV monitoring and disease-control policies in the ROK. [ABSTRACT FROM AUTHOR]

Drawing upon person-environment fit, specifically demands–abilities fit, this paper examines the impact of hospitality employees' cultural intelligence (CQ) on their voice behavior and job satisfaction. Data were collected from domestic contact employees working for restaurants in three major cities in the United States. The results of the PLS-SEM model show that CQ has a positive effect on employees' voice behavior through self-efficacy. Further, CQ has a positive effect on job satisfaction through a sequential mediation of self-efficacy and voice. This study contributes to the CQ and voice literature, utilizing CQ as a person's ability to meet job requirements. This study also has important practical implications for hospitality practitioners who depend on employee voice for the success of organizations in today's ever-changing global environment. [ABSTRACT FROM AUTHOR]

The NLRP3 inflammasome is upregulated by various agents, such as nuclear factor-kappa B (NF-κB), lipopolysaccharide (LPS), and adenosine triphosphate (ATP). The NLRP3 inflammasome facilitations the maturation of interleukin (IL)-1β, a proinflammatory cytokine that is critically involved in the pathogenesis of atopic dermatitis (AD). Although the NLRP3 inflammasome clearly exacerbates AD symptoms such as erythema and pruritus, drugs for AD patients targeting the NLRP3 inflammasome are still lacking. Based on the previous findings that Mentha arvensis essential oil (MAEO) possesses strong anti-inflammatory and anti-AD properties through its inhibition of the ERK/NF-κB signaling pathway, we postulated that MAEO might be capable of modulating the NLRP3 inflammasome in AD. The aim of this research was to investigate whether MAEO affects the inhibition of NLRP3 inflammasome activation in murine bone marrow-derived macrophages (BMDMs) stimulated with LPS + ATP in vitro and in a murine model displaying AD-like symptoms induced by 2,4-dinitrochlorobenzene (DNCB) in vivo. We found that MAEO inhibited the expression of NLRP3 and caspase-1, leading to the suppression of NLRP3 inflammasome activation and IL-1β production in BMDMs stimulated with LPS + ATP. In addition, MAEO exhibited efficacy in ameliorating AD symptoms in a murine model induced by DNCB, as indicated by the reduction in dermatitis score, ear thickness, transepidermal water loss (TEWL), epidermal thickness, and immunoglobulin E (IgE) levels. Furthermore, MAEO attenuated the recruitment of NLRP3-expressing macrophages and NLRP3 inflammasome activation in murine dorsal skin lesions induced by DNCB. Overall, we provide evidence for the anti-AD effects of MAEO via inhibition of NLRP3 inflammasome activation. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, dry skin and redness on the face and inside elbows or knees. Most patients with AD are children and youths, but it can also develop in adults. In the therapeutic aspect, treatment with corticosteroids for AD has several side effects, such as weight loss, atrophy and acne. In the current study, we examined the anti-inflammatory effect of Moringa concanensis leaves on HaCaT keratinocytes and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like symptoms in BALB/c mice. We observed that M. concanensis treatment exhibited significant inhibition in the production of inflammatory mediators and proinflammatory cytokines, such as IL-1β, in LPS-induced HaCaT keratinocytes by downregulating the NLRP3 inflammasome activation. Moreover, M. concanensis inhibited the activation of JNK, AP-1 and p65, which resulted in the deformation of NLRP3 in LPS-stimulated HaCaT cells. In mice with DNCB-induced AD-like skin lesions, the administration of M. concanensis ameliorated the clinical symptoms, such as the dermatitis score, thickness of lesional ear skin and TEWL. Furthermore, M. concanensis could attenuate the activation of the immune system, such as reducing the spleen index, concentration of the IgE levels and expression of the NLRP3 inflammasome in ear tissues. Therefore, our results suggest that M. concanensis exerts anti-atopic dermatitis effects by inhibiting the NLRP3 inflammasome-mediated IL-1β. [ABSTRACT FROM AUTHOR]

Inflammation is an adaptive response to tissue injury, which is a critical process in order to restore tissue functionality and homeostasis. The association between inflammation and cancer has been a topic of interest for many years, not only inflammatory cells themselves but also the chemokines and cytokines they produce, which affect cancer development. Autophagy is an intracellular self-degradative process providing elimination of damaged or dysfunctional organelles under stressful conditions such as nutrient deficiency, hypoxia, or chemotherapy. Interestingly, the signaling pathways that are involved in cancer-associated inflammation may regulate autophagy as well. These are (1) the toll-like receptor (TLR) signaling cascade, (2) the reactive oxygen species (ROS) signaling pathway, (3) the inflammatory cytokine signaling pathway, and (4) the IκB kinase (IKK)/Nuclear factor-κB (NF-κB) signaling axis. Moreover, the studies on the context-specific functions of autophagy during inflammatory responses in cancer will be discussed here. On that basis, we focus on autophagy inhibitors and activators regulating inflammatory process in cancer as useful candidates for enhancing anticancer effects. This review summarizes how the autophagic process regulates these key inflammatory processes and vice versa in various cancers. [ABSTRACT FROM AUTHOR]

This study explored the structural relationships among the physical environment, employee performance, and diners' emotional states, satisfaction, and behavioral intentions, applying the Mehrabian–Russell's theoretical framework in upscale restaurants. Empirical data were collected from 275 upscale restaurant patrons. The results showed that both intangible (employee service) and tangible (physical environment) factors have significant impacts on diners' emotional responses (pleasure and arousal), and these emotional responses affect customer satisfaction and behavioral intentions. This study found that the physical environment exerted a greater impact on arousal than employee behavior while employee behavior had a greater impact on pleasure than physical environment. In addition, arousal was found to have a positive influence on pleasure. We discussed managerial and theoretical implications based on these findings. [ABSTRACT FROM AUTHOR]

Simple Summary: This study evaluates the prognostic capability of the 18fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET)/computed tomography (CT) in patients with anaplastic thyroid cancer (ATC) which can be used as a potential biomarker reflecting glycolysis. ATC is a rare, but highly lethal disease with a one-year overall survival of 20%, and its prognostic factors have rarely been investigated. In this study, survival data correlated with PET/CT derived parameters provide evidence that FDG uptake assessed by PET/CT is a prognostic marker, which may have a clinical impact on the management of patients with ATC. Anaplastic thyroid carcinoma (ATC) is a rare but highly lethal disease. Therefore, its diagnosis at an early stage and a rapid and accurate establishment of a proper treatment strategy is warranted. Tumor glycolysis assessed by 18fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET)/computed tomography (CT) is predictive of many cancers despite its limited proven applicability to ATC. We investigated the prognostic capability of [18F]FDG PET/CT in patients with ATC. Forty patients with ATC were subjected to [18F]FDG PET/CT for pre-treatment evaluation. The tumor size and stage, overall survival (OS), and PET parameters, including the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were analyzed. The 1-year OS rate was 17.5% with a mean life expectancy of 7.1 months. Distant metastasis was detected solely using PET/CT in 37.5% of cases. High SUVmax, MTV, and TLG were significantly associated with poor prognosis (p < 0.001, p = 0.002, and p < 0.001, respectively). A significant difference (p < 0.001) was observed in OS between patients with a high and low tumor SUVmax. Glucose metabolism assessed by [18F]FDG PET/CT was significantly associated with the OS of patients with ATC. PET-derived parameters such as SUVmax, MTV, and TLG are useful prognostic biomarkers for ATC. [ABSTRACT FROM AUTHOR]

Ribes diacanthum Pall, a native Mongolian medicinal plant, has been reported to show antioxidant activities due to its polyphenol and flavonoid content, and is especially rich in the ethyl acetate fraction from an 80% methanol extraction (RDP). We assessed the cytoprotective effect of RDP on glutamate-caused oxidative stress and apoptosis in mouse hippocampal neuronal cells (HT-22 cells). Cell viability was significantly recovered by RDP treatment. Also, RDP effectively decreased the glutamate-induced production of intracellular reactive oxygen species (ROS). In flow cytometric analysis, apoptotic cells and the mitochondrial membrane potential were suppressed by RDP. In the Western blotting analysis, we found that RDP not only decreased the release of apoptotic proteins but also recovered anti-apoptotic protein. Additionally, RDP enhanced the antioxidant defense system by regulating the expression of antioxidant enzymes. Furthermore, treatment with RDP activated the BDNF/TrkB pathway. In accordance with the in vitro results, RDP meliorated memory deficit by defending hippocampal neuronal cells against oxidative damage in scopolamine-injected mice. Taken together, our present study showed that RDP exerted antioxidant and neuroprotective actions against oxidative stress. Therefore, RDP might facilitate the development of candidates for functional health foods for neurodegenerative disorders. [ABSTRACT FROM AUTHOR]

(1) Background: Quantification of platelet division is challenging because automated Coulter cell counters produce equivocal platelet counts. (2) Methods: We applied the flow cytometric cell tracking dye dilution assay as a popular immunological method to evaluate lymphocyte proliferation to prove and quantitate platelet division. We also devised a method relying on platelet culture in a semisolid medium which enabled dividing platelets to be identified by limiting the diffusive movement of platelets. Mixing platelets of different labeling colors in semisolid medium and counting the platelet doublets of each color combination enabled us to prove and quantitate platelet division. (3) Results: The tracking dye dilution assay revealed that 75.5 to 85.6% of platelets were dividing after 20 hours in culture. Platelets labeled with two different tracking dyes were mixed and cultured in semisolid medium for differential doublet counting. We counted platelet singlets and doublets of each color and color combination using confocal microscopy after six hours of culture and compared the relative number of two-colored doublets with binomial prediction to prove platelet division (P < 0.01). Division was suppressed by taxol, nocodazole, or cytochalasin D treatment. We derived a formula for determining the fraction of dividing platelets using the numbers of singlets and doublets of each color and color combination. The platelet division fraction ranged from 8.8 to 17.5%. (4) Conclusion: We successfully measured platelet division using a simple biometric image analysis method with possible future application to microfluidic devices. [ABSTRACT FROM AUTHOR]

Distal-less homeobox 5 (Dlx5) is a negative regulator of adipogenesis. Dlx5 expression is decreased by adipogenic stimuli, but the mechanisms of Dlx5 downregulation by adipogenic stimuli have not yet been determined. Here, we tested the impact of cAMP/PKA (protein kinase A) signaling induced by 3-isobutyl-1 methyl xanthine (IBMX), forskolin, and 8-CPT-cAMP on the expression of Dlx5 in 3T3-L1 preadipocytes. Significant downregulation of Dlx5 mRNA expression and protein production levels were observed via cAMP/PKA-dependent signaling. Forced expression of cAMP-responsive element-binding protein (CREB) and CCAAT/enhancer-binding protein β (C/EBPβ) was sufficient for downregulation of Dlx5 expression and revealed that CREB functions upstream of C/EBPβ. In addition, C/EBPβ knockdown by siRNA rescued Dlx5 expression in IBMX-treated 3T3-L1 preadipocytes. Luciferase assays using a Dlx5-luc-2935 reporter construct demonstrated the requirement of the Dlx5 promoter region, ranging from −774 to −95 bp that contains two putative C/EBPβ binding elements (site-1: −517 to −510 bp and site-2: −164 to −157 bp), in the suppression of Dlx5 transcription. Consequently, chromatin immunoprecipitation analysis confirmed the importance of site-1, but not site-2, in C/EBPβ binding and transcriptional suppression of Dlx5. In conclusion, we elucidated the underling mechanism of Dlx5 downregulation in IBMX-induced adipogenesis. IBMX activated cAMP/PKA/CREB signaling and subsequently upregulated C/EBPβ, which binds to the Dlx5 promoter to suppress Dlx5 transcription. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease influenced by a complex interplay of genetic and environmental factors. The activation of the JAK-STAT pathway increases the expression of inflammatory cytokines such as IL-4 and IL-13, further deteriorating AD. Therefore, for the treatment of AD, the JAK-STAT pathway is emerging as a significant target, alongside inflammatory cytokines. This study investigates the potential therapeutic effects of a novel herbal complex, LK5, composed of Scutellaria baicalensis , Liriope platyphylla , Sophora flavescens , Dictammus dasycarpus , and Phellodendron schneider , known for their anti-inflammatory and immune-modulating properties. We examined the anti-inflammatory and anti-AD effects of the LK5 herbal complex in HaCaT cells stimulated by LPS and IL-4/IL-13, as well as in a mouse model of AD induced by DNCB. In HaCaT cells stimulated with LPS or IL-4/IL-13, the LK5 herbal complex demonstrated anti-inflammatory effects by inhibiting the expression of inflammatory cytokines including TNF-α, IL-6, and IL-1β, and downregulating the phosphorylation of STAT proteins. In a murine AD-like model induced by DNCB, administration of the LK5 herbal complex significantly ameliorated clinical symptoms, including dermatitis, ear thickness, and TEWL. Histological analysis revealed a reduction in epidermal thickness and mast cell infiltration. The LK5 herbal complex also inhibited pruritus induced by compound 48/80. Furthermore, the LK5 herbal complex treatment significantly decreased the levels of inflammatory cytokines such as TSLP, IL-6, and IgE in plasma and ear tissue of AD-induced mice. These findings suggest that the LK5 herbal complex may modulate the immune response and alleviate AD symptoms by inhibiting STAT pathways.

African swine fever (ASF) was first reported in South Korea in September 2019, and as of 31 December 2021, a total of 21 cases in domestic pig farms and 1875 ASFV-infected wild boars have been confirmed in the country. With the continued circulation of ASF in wild boars, and subsequent outbreaks in domestic pigs, concerns were raised about the possible changes in virulence occurring among African swine fever viruses (ASFV) circulating in South Korea. In this study, four Korean ASFV strains isolated from domestic pig farms at different time points between 2019 and 2021 were chosen, and used to experimentally infect domestic pigs by intramuscular inoculation to compare their virulence. All challenged pigs died at 4-9 days post-inoculation, with many showing clinical symptoms of fever, depression, loss of appetite, and recumbency. Gross lesions observed at necropsy included enlargement and hemorrhage of the lymph nodes and hydropericardium. The study showed that all four Korean ASFV isolates caused acute forms of illness, which supports the view that virulence among the circulating ASFV isolates in South Korea remained unchanged and highly virulent during this period.

(1) Background: Quantification of platelet division is challenging because automated Coulter cell counters produce equivocal platelet counts. (2) Methods: We applied the flow cytometric cell tracking dye dilution assay as a popular immunological method to evaluate lymphocyte proliferation to prove and quantitate platelet division. We also devised a method relying on platelet culture in a semisolid medium which enabled dividing platelets to be identified by limiting the diffusive movement of platelets. Mixing platelets of different labeling colors in semisolid medium and counting the platelet doublets of each color combination enabled us to prove and quantitate platelet division. (3) Results: The tracking dye dilution assay revealed that 75.5 to 85.6% of platelets were dividing after 20 hours in culture. Platelets labeled with two different tracking dyes were mixed and cultured in semisolid medium for differential doublet counting. We counted platelet singlets and doublets of each color and color combination using confocal microscopy after six hours of culture and compared the relative number of two-colored doublets with binomial prediction to prove platelet division ( P < 0.01). Division was suppressed by taxol, nocodazole, or cytochalasin D treatment. We derived a formula for determining the fraction of dividing platelets using the numbers of singlets and doublets of each color and color combination. The platelet division fraction ranged from 8.8 to 17.5%. (4) Conclusion: We successfully measured platelet division using a simple biometric image analysis method with possible future application to microfluidic devices.