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BACKGROUND: Atherosclerosis preferentially occurs in arterial regions of disturbed blood flow, and stable flow (s-flow) protects against atherosclerosis by incompletely understood mechanisms. METHODS: Our single-cell RNA-sequencing data using the mouse partial carotid ligation model was reanalyzed, which identified Heart-of-glass 1 (HEG1) as an s-flow-induced gene. HEG1 expression was studied by immunostaining, quantitive polymerase chain reaction, hybridization chain reaction, and Western blot in mouse arteries, human aortic endothelial cells (HAECs), and human coronary arteries. A small interfering RNA-mediated knockdown of HEG1 was used to study its function and signaling mechanisms in HAECs under various flow conditions using a cone-and-plate shear device. We generated endothelial-targeted, tamoxifen-inducible HEG1 knockout (HEG1iECKO) mice. To determine the role of HEG1 in atherosclerosis, HEG1iECKO and littermate-control mice were injected with an adeno-associated virus-PCSK9 [proprotein convertase subtilisin/kexin type 9] and fed a Western diet to induce hypercholesterolemia either for 2 weeks with partial carotid ligation or 2 months without the surgery. RESULTS: S-flow induced HEG1 expression at the mRNA and protein levels in vivo and in vitro. S-flow stimulated HEG1 protein translocation to the downstream side of HAECs and release into the media, followed by increased messenger RNA and protein expression. HEG1 knockdown prevented s-flow-induced endothelial responses, including monocyte adhesion, permeability, and migration. Mechanistically, HEG1 knockdown prevented s-flow-induced KLF2/4 (Kruppel-like factor 2/4) expression by regulating its intracellular binding partner KRIT1 (Krev interaction trapped protein 1) and the MEKK3-MEK5-ERK5-MEF2 pathway in HAECs. Compared with littermate controls, HEG1iECKO mice exposed to hypercholesterolemia for 2 weeks and partial carotid ligation developed advanced atherosclerotic plaques, featuring increased necrotic core area, thin-capped fibroatheroma, inflammation, and intraplaque hemorrhage. In a conventional Western diet model for 2 months, HEG1iECKO mice also showed an exacerbated atherosclerosis development in the arterial tree in both sexes and the aortic sinus in males but not in females. Moreover, endothelial HEG1 expression was reduced in human coronary arteries with advanced atherosclerotic plaques. CONCLUSIONS: Our findings indicate that HEG1 is a novel mediator of atheroprotective endothelial responses to flow and a potential therapeutic target.
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Aterosclerose , Hipercolesterolemia , Placa Aterosclerótica , Masculino , Feminino , Humanos , Camundongos , Animais , Placa Aterosclerótica/metabolismo , Pró-Proteína Convertase 9/metabolismo , Células Endoteliais/metabolismo , Hipercolesterolemia/genética , Aterosclerose/genética , Aterosclerose/prevenção & controle , Aterosclerose/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Proteínas de Membrana/metabolismoRESUMO
BACKGROUND: The process of producing proteins in bacterial systems and secreting them through ATP-binding cassette (ABC) transporters is an area that has been actively researched and used due to its high protein production capacity and efficiency. However, some proteins are unable to pass through the ABC transporter after synthesis, a phenomenon we previously determined to be caused by an excessive positive charge in certain regions of their amino acid sequence. If such an excessive charge is removed, the secretion of any protein through ABC transporters becomes possible. RESULTS: In this study, we introduce 'linear charge density' as the criteria for possibility of protein secretion through ABC transporters and confirm that this criterion can be applied to various non-secretable proteins, such as SARS-CoV-2 spike proteins, botulinum toxin light chain, and human growth factors. Additionally, we develop a new algorithm, PySupercharge, that enables the secretion of proteins containing regions with high linear charge density. It selectively converts positively charged amino acids into negatively charged or neutral amino acids after linear charge density analysis to enable protein secretion through ABC transporters. CONCLUSIONS: PySupercharge, which also minimizes functional/structural stability loss of the pre-mutation proteins through the use of sequence conservation data, is currently being operated on an accessible web server. We verified the efficacy of PySupercharge-driven protein supercharging by secreting various previously non-secretable proteins commonly used in research, and so suggest this tool for use in future research requiring effective protein production.
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Transportadores de Cassetes de Ligação de ATP , Aminoácidos , Humanos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Aminoácidos/metabolismo , Proteínas de Bactérias/metabolismo , Mutação , Sequência de AminoácidosRESUMO
Myosin phosphatase (MP) is an enzyme complex that regulates muscle contraction and plays important roles in various physiological and pathological conditions. Myosin phosphatase targeting subunit (MYPT) 2, a subunit of MP, interacts with protein phosphatase 1c to regulate its phosphatase activity. MYPT2 exists in various isoforms that differ in the composition of essential motifs that contribute to its function. However, regulatory mechanisms underlying these isoforms are poorly understood. Human leukocyte antigen-F adjacent transcript 10 (FAT10) is a ubiquitin-like modifier that not only targets proteins for proteasomal degradation but also stabilizes its interacting proteins. In this study, we investigated the effect of the interaction between FAT10 and MYPT2 isoform a (the canonical full-length form of MYPT2) or MYPT2 isoform f (the natural truncated form of MYPT2). FAT10 interacted with both MYPT2 isoforms a and f; however, only MYPT2 isoform f was increased by FAT10, whereas MYPT2 isoform a remained unaffected by FAT10. We further confirmed that, in contrast to MYPT2 isoform a, MYPT2 isoform f undergoes rapid degradation via the ubiquitin-proteasome pathway and that FAT10 stabilizes MYPT2 isoform f by inhibiting its ubiquitination. Therefore, our findings suggest that the interaction between FAT10 and MYPT2 isoforms leads to distinct stabilization effects on each isoform, potentially modulating MP activity.
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Ubiquitina , Ubiquitinas , Humanos , Fosfatase de Miosina-de-Cadeia-Leve/metabolismo , Isoformas de Proteínas/metabolismo , Proteína Fosfatase 1/metabolismo , Ubiquitina/metabolismo , Ubiquitinação , Ubiquitinas/metabolismoRESUMO
KEY MESSAGE: PAP-FcK and PSA-FcK prostate cancer antigenic proteins transiently co-expressed in plant induce their specific humoral immune responses in mice. Prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) have been considered as immunotherapeutic antigens for prostate cancer. The use of a single antigenic agent is unlikely to be effective in eliciting immunotherapeutic responses due to the heterogeneous and multifocal nature of prostate cancer. Thus, multiple antigens have been combined to enhance their anti-cancer effects. In the current study, PSA and PAP were fused to the crystallizable region (Fc region) of immunoglobulin G1 and tagged with KDEL, the endoplasmic reticulum (ER) retention signal motif, to generate PSA-FcK and PAP-FcK, respectively, and were transiently co-expressed in Nicotiana benthamiana. Western blot analysis confirmed the co-expression of PSA-FcK and PAP-FcK (PSA-FcK + PAP-FcK) with a 1:3 ratios in the co-infiltrated plants. PSA-FcK, PAP-FcK, and PSA-FcK + PAP-FcK proteins were successfully purified from N. benthamiana by protein A affinity chromatography. ELISA showed that anti-PAP and anti-PSA antibodies successfully detected PAP-FcK and PSA-FcK, respectively, and both detected PSA-FcK + PAP-FcK. Surface plasmon resonance (SPR) analysis confirmed the binding affinity of the plant-derived Fc fusion proteins to FcγRI/CD64. Furthermore, we also confirmed that mice injected with PSA-FcK + PAP-FcK produced both PSA- and PAP-specific IgGs, demonstrating their immunogenicity. This study suggested that the transient plant expression system can be applied to produce the dual-antigen Fc fusion protein (PSA-FcK + PAP-FcK) for prostate cancer immunotherapy.
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Vacinas Anticâncer , Neoplasias da Próstata , Animais , Humanos , Masculino , Camundongos , Fosfatase Ácida/genética , Fosfatase Ácida/metabolismo , Vacinas Anticâncer/uso terapêutico , Imunidade , Próstata/metabolismo , Antígeno Prostático Específico , Neoplasias da Próstata/terapiaRESUMO
Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheumatoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and ethnicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast-myofibroblast transition, epithelial-mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the histopathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.
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Artrite Reumatoide , Doenças Pulmonares Intersticiais , Masculino , Animais , Humanos , Feminino , Fosfatidilinositol 3-Quinases , Artrite Reumatoide/complicações , Artrite Reumatoide/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Doenças Pulmonares Intersticiais/epidemiologia , Fatores de Risco , Fator ReumatoideRESUMO
Oxytocin and vasopressin are neurohypophyseal hormones with sequence similarity and play a central role in bodily homeostatic regulation. Pain is currently understood to be an important phenotype that those two neurohormones strongly downregulate. Nociceptors, the first component of the ascending neural circuit for pain signals, have constantly been shown to be modulated by those peptides. The nociceptor modulation appears to be critical in pain attenuation, which has led to a gradual increase in scientific interest about their physiological processes and also drawn attention to their translational potentials. This review focused on what are recently understood and stay under investigation in the functional modulation of nociceptors by oxytocin and vasopressin. Effort to produce a nociceptor-specific view could help to construct a more systematic picture of the peripheral pain modulation by oxytocin and vasopressin.
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Nociceptores , Ocitocina , Humanos , Dor , Receptores de Ocitocina , Receptores de Vasopressinas , VasopressinasRESUMO
Jasmonic acid (JA) and ethylene (ET) signaling modulate plant defense against necrotrophic pathogens in a synergistic and interdependent manner, while JA and ET also have independent roles in certain processes, e.g. in responses to wounding and flooding, respectively. These hormone pathways lead to transcriptional reprogramming, which is a major part of plant immunity and requires the roles of transcription factors. ET response factors are responsible for the transcriptional regulation of JA/ET-responsive defense genes, of which ORA59 functions as a key regulator of this process and has been implicated in the JA-ET crosstalk. We previously demonstrated that Arabidopsis (Arabidopsis thaliana) GDSL LIPASE 1 (GLIP1) depends on ET for gene expression and pathogen resistance. Here, promoter analysis of GLIP1 revealed ERELEE4 as the critical cis-element for ET-responsive GLIP1 expression. In a yeast one-hybrid screening, ORA59 was isolated as a specific transcription factor that binds to the ERELEE4 element, in addition to the well-characterized GCC box. We found that ORA59 regulates JA/ET-responsive genes through direct binding to these elements in gene promoters. Notably, ORA59 exhibited a differential preference for GCC box and ERELEE4, depending on whether ORA59 activation is achieved by JA and ET, respectively. JA and ET induced ORA59 phosphorylation, which was required for both activity and specificity of ORA59. Furthermore, RNA-seq and virus-induced gene silencing analyses led to the identification of ORA59 target genes of distinct functional categories in JA and ET pathways. Our results provide insights into how ORA59 can generate specific patterns of gene expression dynamics through JA and ET hormone pathways.
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Proteínas de Arabidopsis/genética , Arabidopsis/genética , Ciclopentanos/metabolismo , Etilenos/metabolismo , Oxilipinas/metabolismo , Imunidade Vegetal/genética , Fatores de Transcrição/genética , Arabidopsis/imunologia , Proteínas de Arabidopsis/metabolismo , DNA de Plantas/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Fatores de Transcrição/metabolismoRESUMO
Cracking and erosion are critical factors that reduce the mechanical properties and stability of concrete structures and soil, respectively. They are recognized worldwide as severe disasters causing the collapse of many structures including stone heritage and dams, and landslides. Therefore, it is essential to propose effective and environment-friendly management methods to prevent them. Carbonatogenesis has recently received considerable attention as a reliable biological process for remediating cracks in calcareous structures, stabilizing loose soils, and sequestering CO2 in the environment. Isolating and characterizing carbonatogenic bacteria with excellent performance is crucial for applying this process to the field of environmental and civil engineering. The aim of this study was to isolate new CaCO3-precipitating bacteria and investigate various properties for their use as bioconsolidants. Furthermore, the possibility of restoring damaged structures and stabilizing loose sandy soil using isolated strain was investigated. Strain LC13 with urease and CaCO3-precipitating activity was isolated from limestone cave soil in Korea and identified as Arthrobacter sulfureus by phenotypic characterization and 16S rRNA gene analysis. Although cell growth was observed after an adaptation period at pH 11, strain LC13 grew well at pH 7-11, indicating alkali tolerance. The optimal conditions for CaCO3 precipitation were 1.0% yeast extract, 2.5% urea, 0.35% NaHCO3, and 400 mM CaCl2, with an initial pH of 6.5 at 30 °C. Under optimized conditions, maximal CaCO3 (22.92 ± 0.14 g/l) precipitated after 3 days, which was 10.8-fold higher than the value in a urea-CaCl2 medium. CaCO3 precipitation by strain LC13 was associated with an increased pH due to ureolysis and protein deamination. Using an optimized medium as a cementation solution, strain LC13 completely remediated 340-760 µm wide cracks over 3 days, and also restored the spalling of concrete surfaces. Furthermore, the sand treated with LC13 solidified with a surface strength of 14.9 kPa. Instrumental analysis confirmed that the crystals precipitated were a mixture of CaCO3 polymorphs composed of rhombohedral calcite and spherical vaterite. These results suggest that A. sulfureus LC13 may be useful for implementing sustainable biorestoration and environmental management technologies such as the in situ remediation of structural cracks and in situ prevention of soil erosion.
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Álcalis , Erosão do Solo , Álcalis/metabolismo , Bactérias/genética , Bactérias/metabolismo , Carbonato de Cálcio/química , Cloreto de Cálcio/metabolismo , RNA Ribossômico 16S/genética , Solo/química , UreiaRESUMO
With the outbreak of COVID-19, the video game console market is thriving again. In this study, we attempted to explore users' intention to use video game consoles by developing a causal model mainly based on coolness theory and the technology acceptance model. To better illustrate user experience for video game consoles, we added several concepts to the causal model, including hedonic motivation, system and service quality, perceived cost, and game variety. Through examining survey-based data from 360 Koreans, we discovered that the model had a high explanatory power for users' intention to use video game consoles. The key findings were as follows: First, among the components of coolness theory, individuals' attitude toward consoles was significantly related to subcultural appeal and originality, but not to attractiveness. Second, originality positively influenced subcultural appeal significantly. Overall, this study implied that the novel coolness theory is effective for exploring user experience regarding of specific devices and services.
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Dipeptidyl peptidase 4 (DPP4) expression is increased in the lungs of chronic obstructive pulmonary disease (COPD). DPP4 is known to be associated with inflammation in various organs, including LPS-induced acute lung inflammation. Since non-typeable Haemophilus influenzae (NTHi) causes acute exacerbations in COPD patients, we examined the contribution of DPP4 in NTHi-induced lung inflammation in COPD. Pulmonary macrophages isolated from COPD patients showed higher expression of DPP4 than the macrophages isolated from normal subjects. In response to NTHi infection, COPD, but not normal macrophages show a further increase in the expression of DPP4. COPD macrophages also showed higher expression of IL-1ß, and CCL3 responses to NTHi than normal, and treatment with DPP4 inhibitor, diprotin A attenuated this response. To examine the contribution of DPP4 in NTHi-induced lung inflammation, COPD mice were infected with NTHi, treated with diprotin A or PBS intraperitoneally, and examined for DPP4 expression, lung inflammation, and cytokine expression. Mice with COPD phenotype showed increased expression of DPP4, which increased further following NTHi infection. DPP4 expression was primarily observed in the infiltrated inflammatory cells. NTHi-infected COPD mice also showed sustained neutrophilic lung inflammation and expression of CCL3, and this was inhibited by DPP4 inhibitor. These observations indicate that enhanced expression of DPP4 in pulmonary macrophages may contribute to sustained lung inflammation in COPD following NTHi infection. Therefore, inhibition of DPP4 may reduce the severity of NTHi-induced lung inflammation in COPD.
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Dipeptidil Peptidase 4/metabolismo , Infecções por Haemophilus/enzimologia , Haemophilus influenzae/patogenicidade , Macrófagos Alveolares/enzimologia , Pneumonia Bacteriana/enzimologia , Doença Pulmonar Obstrutiva Crônica/enzimologia , Idoso , Animais , Estudos de Casos e Controles , Quimiocina CCL20/metabolismo , Quimiocina CCL3/metabolismo , Modelos Animais de Doenças , Feminino , Infecções por Haemophilus/microbiologia , Interações Hospedeiro-Patógeno , Humanos , Interleucina-1beta/metabolismo , Macrófagos Alveolares/microbiologia , Masculino , Camundongos , Pessoa de Meia-Idade , Pneumonia Bacteriana/microbiologia , Doença Pulmonar Obstrutiva Crônica/microbiologiaRESUMO
Biomineralization, a well-known natural phenomenon associated with various microbial species, is being studied to protect and strengthen building materials such as concrete. We characterized Rhodococcus erythreus S26, a novel urease-producing bacterium exhibiting CaCO3-forming activity, and investigated its ability in repairing concrete cracks for the development of environment-friendly sealants. Strain S26 grown in solid medium formed spherical and polygonal CaCO3 crystals. The S26 cells grown in a urea-containing liquid medium caused culture fluid alkalinization and increased CaCO3 levels, indicating that ureolysis was responsible for CaCO3 formation. Urease activity and CaCO3 formation increased with incubation time, reaching a maximum of 2054 U/min/mL and 3.83 g/L, respectively, at day four. The maximum CaCO3 formation was achieved when calcium lactate was used as the calcium source, followed by calcium gluconate. Although cell growth was observed after the induction period at pH 10.5, strain S26 could grow at a wide range of pH 4-10.5, showing its high alkali tolerance. FESEM showed rhombohedral crystals of 20-60 µm in size. EDX analysis indicated the presence of calcium, carbon, and oxygen in the crystals. XRD confirmed these crystals as CaCO3 containing calcite and vaterite. Furthermore, R. erythreus S26 successfully repaired the artificially induced large cracks of 0.4-0.6 mm width.
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Carbonato de Cálcio/metabolismo , Materiais de Construção/microbiologia , Rhodococcus/metabolismo , Álcalis , Biomineralização/fisiologia , Carbonato de Cálcio/química , Precipitação QuímicaRESUMO
The cancer/testis (CT) antigen NY-SAR-35 gene is located on the X chromosome and is aberrantly expressed in various cancers but not in normal tissues, other than testes. Previously, we reported the expression of NY-SAR-35 enhanced cell growth, proliferation, and invasion in HEK293 and cancer cells. To extend understanding of the NY-SAR-35 gene, we used a next generation sequencing (NGS) approach. NY-SAR-35 expression induced growth, proliferation, metastasis, and stemness genes, as indicated by the up-regulations of CXCR4, EpCAM, CD133, and CD44, at the mRNA and protein levels. The expression of NY-SAR-35 in HEK293 cells significantly increased ERK phosphorylation, but not the phosphorylation of AKT. In HEK293/NY-SAR-35 cells, the expressions of pro-apoptotic proteins, including p53, Bax, and p21, were reduced and that of cyclin E was increased. Also, NY-SAR-35 increased the expressions of pluripotency genes (Nanog, Oct-4, and Sox2) and the ability of HEK293 cells to form colonies. Taken together, the present study indicates NY-SAR-35 functions as a CT antigen that triggers oncogenesis and self-renewal.
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Antígeno AC133/metabolismo , Antígenos de Neoplasias/fisiologia , Molécula de Adesão da Célula Epitelial/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Receptores de Hialuronatos/metabolismo , Antígeno AC133/genética , Molécula de Adesão da Célula Epitelial/genética , Regulação da Expressão Gênica/fisiologia , Células HEK293 , Humanos , Receptores de Hialuronatos/genética , Regulação para CimaRESUMO
A catalytic highly enantioselective Mannich/aza-Michael cascade reaction of δ-formyl-α,ß-unsaturated ketones with cyclic N-sulfimines, promoted by diphenylprolinol TMS ether as an organocatalyst, has been developed for the synthesis of chiral benzosulfamidate-fused pyrrolidines, which generated in good yields and with high diastero- and enantioselectivities. Further chemical transformations have been performed with chiral benzosulfamidate-fused pyrrolidines.
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Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disorder affecting the temporomandibular joint (TMJ), marked by persistent inflammation and structural damage to the joint. Only symptomatic treatment is available for managing TMJOA. Human umbilical cord mesenchymal stem cells (hUC-MSCs) show potential for treating TMJOA via their immune-modulating actions in the disease area. In addition, stimulation of inflammatory cytokines such as interferon-gamma in hUC-MSCs improves the therapeutic activity of naïve stem cells. Emerging evidence indicates that macrophages play significant roles in regulating joint inflammation through diverse secreted mediators in the pathogenesis of TMJOA. This study was conducted to evaluate the effects of inflammatory cytokine-stimulated hUC-MSCs in repairing TMJOA-induced cartilage lesions and the role of macrophages in the disease. Our in vitro data showed that stimulated hUC-MSCs induce M2 polarization of macrophages and enhance the expression of anti-inflammatory molecules. These effects were subsequently validated in vivo. In a rat model of TMJOA, stimulated hUC-MSCs ameliorated inflammation and increased M2 macrophages ratio. Our results indicate that hUC-MSCs stimulated by inflammatory cytokines modulate the activation of M2 macrophages, thereby shifting the local osteoarthritis microenvironment toward a prochondrogenic state and facilitating cartilage repair in inflammatory conditions. Stimulating hUC-MSCs with inflammatory cytokines could potentially offer an effective therapeutic approach for TMJOA, with macrophages playing a pivotal role in immune modulation.
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BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease affecting the cartilage and subchondral bone, leading to temporomandibular joint pain and dysfunction. The complex nature of TMJOA warrants effective alternative treatments, and mesenchymal stem cells (MSCs) have shown promise in regenerative therapies. The aim of this study is twofold: firstly, to ascertain the optimal interferon-gamma (IFN-γ)-primed MSC cell line for TMJOA treatment, and secondly, to comprehensively evaluate the therapeutic efficacy of IFN-γ-primed mesenchymal stem cells derived from the human umbilical cord matrix in a rat model of TMJOA. METHODS: We analyzed changes in the expression of several key genes associated with OA protection in MSC-secreted compounds. Following this, we performed co-culture experiments using a transwell system to predict gene expression changes in primed MSCs in the TMJOA environment. Subsequently, we investigated the efficacy of the selected IFN-γ-primed human umbilical cord matrix-derived MSCs (hUCM-MSCs) for TMJOA treatment in a rat model. RESULTS: IFN-γ-primed MSCs exhibited enhanced expression of IDO, TSG-6, and FGF-2. Moreover, co-culturing with rat OA chondrocytes induced a decrease in pro-inflammatory and extracellular matrix degradation factors. In the rat TMJOA model, IFN-γ-primed MSCs with elevated IDO1, TSG-6, and FGF2 expression exhibited robust anti-inflammatory and therapeutic capacities, promoting the improvement of the inflammatory environment and cartilage regeneration. CONCLUSION: These findings underscore the importance of prioritizing the mitigation of the inflammatory milieu in TMJOA treatment and highlight IFN-γ-primed MSCs secreting these three factors as a promising, comprehensive therapeutic strategy.
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Células-Tronco Mesenquimais , Osteoartrite , Humanos , Ratos , Animais , Interferon gama/metabolismo , Interferon gama/farmacologia , Articulação Temporomandibular , Cordão Umbilical , Células-Tronco Mesenquimais/metabolismo , Osteoartrite/terapiaRESUMO
Flavonoids have extensive biological qualities that support human health. A molecular networking strategy produced representative networks despite mass fragmentation of spectra of untargeted data-dependent acquisition approach to target flavonoid glycosides from Vicia bungei by using UHPLC-MS guided isolation. Using contemporary methods, seven chemicals were extracted and identified. Antioxidative and anti-inflammatory effects of these isolates were assessed in vitro on free radicals and inflammatory mediators, cytokines, enzymatic proteins. Two active compounds, apigenin 6-C-ß-D-galactopyranosyl-8-C-ß-D-xylopyranoside, and sphaerobioside, were further assessed for their binding affinity to target protein in in silico study. The molecular mechanism of sphaerobioside was found to involve suppression of LPS-stimulated inflammation by NF-κB inactivation by inhibiting nuclear translocation of p65 and prevention of phosphorylation of κB inhibitor α (IκBα) and IκB kinase (IKKα/ß). Furthermore, an analytical method was successfully established and employed to quantify the total extract using these seven chemicals present in this plant as markers.
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Anti-Inflamatórios , Flavonoides , Frutas , Glicosídeos , Compostos Fitoquímicos , Extratos Vegetais , Glicosídeos/química , Glicosídeos/farmacologia , Frutas/química , Flavonoides/química , Flavonoides/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Humanos , NF-kappa B/metabolismo , AnimaisRESUMO
We introduce three newly designed thermally cross-linkable hole transport copolymers (PIF-TPD, PIF-F2PCz, and PIF-TPAPCz) for improving the performance of solution-processed organic light-emitting diodes (s-OLEDs). These copolymers, designed through a strategic molecular approach with benzocyclobutene (BCB) and styrene-based cross-linking monomers, show high solvent resistance at a low cross-linking temperature (150 °C). Furthermore, these conjugated copolymers based on planar indenofluorene with three different hole transport (HT) units, exhibit outstanding charge carrier mobility (1.61 × 10-2 cm2 V-1s-1), demonstrated by comparing hole reorganization energy and electronic coupling strength of HT units. Despite these copolymers showing the overall vertical orientation in the horizontal dipole moment measurement results, we demonstrated that the HT units can exhibit the preferred orientation, contributing to high hole transport properties. As a result, they perform exceptionally well as hole transport layers in green phosphorescent s-OLEDs, achieving a maximum external quantum efficiency of 15.3% and a maximum current efficiency of 53.9 cd A-1 with a small efficiency roll-off despite their relatively low triplet energy levels. These results are comparable to vacuum-deposited OLEDs, highlighting the potential of these copolymers in advancing OLED technology for display panels and lighting applications.
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BACKGROUND/OBJECTIVES: The umami taste receptor (TAS1R1/TAS1R3) is endogenously expressed in skeletal muscle and is involved in myogenesis; however, there is a lack of evidence about whether the expression of the umami taste receptor is involved in muscular diseases. This study aimed to elucidate the effects of the umami taste receptor and its mechanism on muscle wasting in cancer cachexia using in vivo and in vitro models. MATERIALS/METHODS: The Lewis lung carcinoma-induced cancer cachexia model was used in vivo and in vitro, and the expressions of umami taste receptor and muscle atrophy-related markers, muscle atrophy F-box protein, and muscle RING-finger protein-1 were analyzed. RESULTS: Results showed that TAS1R1 was significantly downregulated in vivo and in vitro under the muscle wasting condition. Moreover, overexpression of TAS1R1 in vitro in the human primary cell model protected the cells from muscle atrophy, and knockdown of TAS1R1 using siRNA exacerbated muscle atrophy. CONCLUSION: Taken together, the umami taste receptor exerts protective effects on muscle-wasting conditions by restoring dysregulated muscle atrophy in cancer cachexia. In conclusion, this result provided evidence that the umami taste receptor exerts a therapeutic anti-cancer cachexia effect by restoring muscle atrophy.
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As the chemical stability of organic materials in organic light-emitting diodes (OLEDs) greatly impacts devices' lifetime, a thoughtful and advanced design of materials and device structures is necessary. In our work, we have achieved lifetime enhancement at its initial stage for solution-processed OLEDs. This improvement was realized through the implementation of a double electron transporting layer (dETL) composed of 2-[4-(9,10-dinaphthalen-2-yl-anthracen-2-yl)-phenyl]-1-phenyl-1H-benzoimidazole (ET) and hydroxyquinolinolato-lithium (Liq). A giant surface potential was generated at the surface of a constituent electron transport layer (ETL) that contained a higher concentration of Liq with high polarity. This giant surface potential simultaneously promoted the injection of trapped/accumulated electrons through the interface within dETL and the injection of holes from the anode, generating more exciton recombination events and ultimately enhancing efficiency by 133.0% and lifetime LT95 (luminance dropped by 5%) by 300% with an overshooting effect. Additionally, the degradation at the emitting layer was mitigated by shifting the degradation zone to the dETL, which was evidenced by laser desorption/ionization-time-of-flight (LDI-TOF) mass spectroscopy.
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In this study, the effects of a 12-month multidisciplinary education program on the health status, dietary quality, and eating habits of children and adolescents attending community childcare centers were investigated. A total of 88 participants aged 7 to 17 years from 7 community childcare centers in Gyeonggi-do were enrolled. The intervention consisted of 12 multidisciplinary education sessions covering topics such as nutrition, exercise, and psychological education. All participants received the same education, and the effectiveness of the program was evaluated by categorizing them into a high participation group (HPG) and a low participation group (LPG) based on their participation rates. After intervention, in physical activities, moderate-intensity exercise was significantly reduced in the LPG, and there was no significant difference in psychological parameters. However, notable differences were observed in nutritional data. After intervention, intakes of calorie, carbohydrate, protein, and fat were significantly increased in both groups, and in particular, the change was found to be greater in HPG. Additionally, dietary fiber intake compared to the 2015 Korean Dietary Reference Intakes was increased in both groups. Daily food intake also increased dietary fiber intake in HPG, and meat and fruit intake was increased in LPG. In the nutrition quotient, there was a significant difference in HPG's pre- and post-scores in the diversity category, and in nutrient adequacy ratio (NAR), the NAR of phosphorus was increased in both groups. The findings of this study suggest that multidisciplinary education implemented at community childcare centers primarily enhanced nutrition-related factors rather than physical activity or psychological aspects. Trial Registration: Clinical Research Information Service Identifier: KCT0002718.