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ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (G. lucidum) has been widely used as adjuvant of anti-tumor therapy for variety tumors. The bioactive ingredients of G. lucidum mainly include triterpenes, such as Ganoderic acid A, Ganoderic acid B, Ganoderenic acid A, Ganoderenic acid B, Ganoderenic acid D, and Ganoderic acid X. However, the effects and underlying mechanisms of G. lucidum are often challenging in hepatocellular carcinoma (HCC) treatment. AIM OF THE STUDY: To explore the potential role and mechanism of enhancer-associated lncRNAs (en-lncRNAs) in G. lucidum treated HCC through the in vivo and in vitro experiments. MATERIALS AND METHODS: Hepa1-6-bearing C57 BL/6 mice model were established to evaluate the therapeutic efficacy of G. lucidum treated HCC. Ki67 and TUNEL staining were used to detect the tumor cell proliferation and apoptosis in vivo. The Mouse lncRNA 4*180K array was implemented to identify the differentially expressed (DE) lncRNAs and mRNAs of G. lucidum treated tumor mice. The constructed lncRNA-mRNA co-expression network and bioinformatics analysis were used to selected core en-lncRNAs and its neighboring genes. The UPLC-MS method was used to identify the triterpenes of G. lucidum, and the in vitro experiments were used to verify which triterpene monomers regulated en-lncRNAs in tumor cells. Finally, a stable knockdown/overexpression cell lines were used to confirm the relationship between en-lncRNA and neighboring gene. RESULTS: Ki67 and TUNEL staining demonstrated G. lucidum significantly inhibited tumor growth, suppressed cell proliferation and induced apoptosis in vivo. Transcriptomic analysis revealed the existence of 126 DE lncRNAs high correlated with 454 co-expressed mRNAs in G. lucidum treated tumor mice. Based on lncRNA-mRNA network and qRT-PCR validation, 6 core lncRNAs were selected and considered high correlated with G. lucidum treatment. Bioinformatics analysis revealed FR036820 and FR121302 might act as enhancers, and qRT-PCR results suggested FR121302 might enhance Popdc2 mRNA level in HCC. Furthermore, 6 main triterpene monomers of G. lucidum were identified by UPLC-MS method, and in vitro experiments showed FR121302 and Popdc2 were significantly suppressed by Ganoderenic acid A and Ganoderenic acid B, respectively. The knock/overexpression results demonstrated that FR121302 activating and enhancing Popdc2 expression levels, and Ganoderenic acid A and Ganoderenic acid B dramatically suppressed FR121302 and decreased Popdc2 level in Hepa1-6 cells. CONCLUSIONS: Enhancer-associated lncRNA plays a crucial role as an enhancer during hepatocarcinogenesis, and triterpenes of G. lucidum significantly inhibited tumor cell proliferation and induced apoptosis by regulating en-lncRNAs. Our study demonstrated Ganoderenic acid A and Ganoderenic acid B suppressed en-lncRNA FR121302 may be one of the critical strategies of G. lucidum inhibit hepatocellular carcinoma growth.
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Apoptose , Carcinoma Hepatocelular , Proliferação de Células , Neoplasias Hepáticas , Camundongos Endogâmicos C57BL , RNA Longo não Codificante , Reishi , Triterpenos , Animais , Triterpenos/farmacologia , Triterpenos/isolamento & purificação , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/genética , Reishi/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Masculino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificaçãoRESUMO
OBJECTIVES: To compare the image quality and efficacy of the Adaptive imaging receiver (AIR)TM coil (GE Healthcare) and the traditional coil for multiplexed sensitivity encoding diffusion-weighted imaging (MUSE-DWI) in the detection of focal liver lesions (FLLs). METHODS: Two groups of MUSE-DWI were obtained. Image quality was qualitatively evaluated by three independent blinded radiologists on a 5-point scale, and quantitative parameters were calculated by measurements of the region of interest in the liver and FLLs. McNemar's test was used to compare the characteristics and detectability. RESULTS: Less image noise, sharper contours, milder susceptibility artifacts, and better liver lesion conspicuity were found by all radiologists in 60 livers with 140 FLLs with the AIR coil than with the traditional coil (reader average mean, 4.3-4.4 vs. 3.7-4.0, P < 0.001). The signal-to-noise ratio (SNR) of the liver was significantly higher with the AIR coil than with the traditional coil (right lobe: mean, 8.89 vs.7.76, P < 0.05; left lobe: mean, 7.14 vs.6.19, P < 0.001), and the SNR of FLLs (mean, 24.62 vs. 21.01, P < 0.001) and lesion-to-liver CNR (mean, 16.61 vs. 14.02, P < 0.001) exhibited significant differences between the AIR coil and the traditional coil. Besides, superior detection of FLLs was observed with the AIR coil compared to the traditional coil (95.7% [134/140] vs. 85.7% [120/140], P < 0.001). CONCLUSIONS: The AIR coil yields less noise, fewer distortions, better lesion detectability, higher SNR of the liver and FLLs, and improved lesion-to-liver CNR during liver MUSE-DWI. Thus, it is a feasible and eï¬ective scanning scheme in liver MRI. ADVANCES IN KNOWLEDGE: The AIR coil improves SNR and the quality of liver MR imaging compared with the traditional coil.
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In this paper, we demonstrate a facile way to prepare polymeric microlens arrays (MLAs) based on a discontinuous wetting surface using a self-assembly technique. A patterned hydrophobic-octadecyltrichlorosilane (OTS) surface was prepared by U V/O 3 irradiation through a shadow mask. The area exposed to U V/O 3 irradiation turned highly hydrophilic, whereas the area protected by the mask remained highly hydrophobic, generating the patterned OTS surface. The surface energy of the OTS/glass surface changed from 23 to 72.8 mN/m after 17 min of U V/O 3 treatment. The scribing of the optical glue-NOA 81 onto the microhole array enabled one to obtain the MLAs due to the generation of the NOA 81 droplet array via the surface tension. After UV light curing, the cured NOA 81 droplet array with uniform dimensions within a large area exhibited excellent MLA characteristics. Moreover, the method developed in this study is simple in operation, low-cost, and requires neither a clean room nor expensive equipment.
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Anastomose Cirúrgica , Colectomia , Constipação Intestinal , Intussuscepção , Laparoscopia , Reto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anastomose Cirúrgica/métodos , Colectomia/métodos , Colectomia/efeitos adversos , Constipação Intestinal/cirurgia , Constipação Intestinal/etiologia , Doenças do Íleo/cirurgia , Doenças do Íleo/etiologia , Íleo/cirurgia , Intussuscepção/cirurgia , Laparoscopia/métodos , Complicações Pós-Operatórias/etiologia , Reto/cirurgia , Resultado do TratamentoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: As a common chronic inflammatory skin disease, psoriasis is incompletely understood and brings a lot of distress to patients. The estrogen signaling pathway has been implicated in its pathogenesis, making it a potential therapeutic target. Si Cao Formula (SCF) has demonstrated promise in treating psoriasis clinically. However, its molecular mechanisms concerning psoriasis remain largely unexplored. AIM OF THE STUDY: To elucidate the underlying mechanisms of the action of SCF on psoriasis. MATERIALS AND METHODS: Active ingredients were identified by LC-MS/MS. After the treatment with SCF, the exploration of differentially expressed proteins (DEPs) were conducted using tandem mass tag (TMT)-based quantitative proteomics analysis. By GO/KEGG, WikiPathways and network pharmacology, core signaling pathway and protein targets were explored. Consequently, major signaling pathway and protein targets were validated by RT-qPCR, immunoblotting and immunofluorescence. Based on Lipinski's Rule of Five rules and molecular docking, 8 active compounds were identified that acted on the core targets. RESULTS: 41 compounds of SCF and 848 specific targets of these compounds were identified. There were 570 DEPs between IMQ (Imiquimod) and IMQ + SCF group, including 279 up-regulated and 304 down-regulated proteins. GO/KEGG, WikiPathways and network pharmacology revealed estrogen signaling pathway as the paramount pathways, through which SCF functioned on psoriasis. We further show novel ingredients formula of SCF contributes to estrogen signaling intervention, including liquiritin, parvisoflavone B, glycycoumarin, 8-prenylluteone, licochalcone A, licochalcone B, oxymatrine, and 13-Hydroxylupanine, where targeting MAP2K1, ILK, HDAC1 and PRKACA, respectively. Molecular docking proves that they have good binding properties. CONCLUSION: Our results provide an in-depth view of psoriasis pathogenesis and herbal intervention, which expands our understanding of the systemic pharmacology to reveal the multiple ingredients and multiple targets of SCF and focus on one pathway (estrogen signaling pathway) may be a novel therapeutic strategy for psoriasis treatment of herbal medicine.
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Medicamentos de Ervas Chinesas , Estrogênios , Simulação de Acoplamento Molecular , Farmacologia em Rede , Psoríase , Transdução de Sinais , Psoríase/tratamento farmacológico , Psoríase/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Estrogênios/farmacologia , Estrogênios/metabolismo , Células HaCaT , Proteômica/métodosRESUMO
Influenza virus infection is a worldwide challenge that causes heavy burdens on public health. The mortality rate of severe influenza patients is often associated with hyperactive immunological abnormalities characterized by hypercytokinemia. Due to the continuous mutations and the occurrence of drug-resistant influenza virus strains, the development of host-directed immunoregulatory drugs is urgently required. Platycodon grandiflorum is among the top 10 herbs of traditional Chinese medicine used to treat pulmonary diseases. As one of the major terpenoid saponins extracted from Platycodon grandiflorum, Platycodin D (PD) has been reported to play several roles, including anti-inflammation, analgesia, anti-cancer, hepatoprotection, and immunoregulation. However, the therapeutic roles of PD to treat influenza virus infection remains unknown. Here, we show that PD can protect the body weight loss in severely infected influenza mice, alleviate lung damage, and thus improve the survival rate. More specifically, PD protects flu mice via decreasing the immune cell infiltration into lungs and downregulating the overactivated inflammatory response. Western blot and immunofluorescence assays exhibited that PD could inhibit the activation of TAK1/IKK/NF-κB and MAPK pathways. Besides that, CETSA, SPR and immunoprecipitation assays indicated that PD binds with TRAF6 to decrease its K63 ubiquitination after R837 stimulation. Additionally, siRNA interference experiments exhibited that PD could inhibit the secretion of IL-1ß and TNF-α in TRAF6-dependent manner. Altogether, our results suggested that PD is a promising drug candidate for treating influenza. Our study also offered a scientific explanation for the commonly used Platycodon grandiflorum in many anti-epidemic classic formulas. Due to its host-directed regulatory role, PD may serve as an adjuvant therapeutic drug in conjunction with other antiviral drugs to treat the flu.
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Social integration, a huge issue triggered by migration, leads to potential social fragmentation and confrontation. Focusing on the precise enhancement of "inner" subjective social integration is the ultimate urbanization solution to enhance people-centered well-being and promote full social integration. This article used data from the China Migrants Dynamic Survey 2017 (CMDS 2017) to reveal the spatial patterns and mechanisms of subjective social integration in Chinese cities. We make an innovative attempt to introduce multiscale geographically weighted regression (MGWR) to address the appropriateness of policy formulation by addressing the spatial variation in the factors. The results demonstrate that the influences on subjective social integration have a strong spatial heterogeneity in China, a vast and unevenly developed country. Expanding on the typical factors, household registration and political participation affect North China more than other regions; and housing and marriage have a greater impact in South China, especially in the Pearl River Delta and the Eastern Seaboard. Income, welfare, and healthcare are indiscriminately sweeping through most of China. Such a conclusion reminds the Chinese government that it needs to consider not only addressing some of the national constraints to subjective social integration but also imposing precise, site-specific changes for different regions.
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Migrantes , Humanos , Cidades , Urbanização , Povo Asiático , Integração SocialRESUMO
A dielectric liquid microlens array (LMA) with a tunable focal length was fabricated by using a microdroplet array generated through the dip-coating method. The process began with treating the octadecyltrichlorosilane (OTS) layer with selective UV/O3 irradiation for 20 min to establish a hydrophilic-hydrophobic patterning surface. The substrate was subsequently immersed in glycerol and then withdrawn at a constant rate to create a microdroplet array. Upon filling the cell with matching oil (SL5267) and placing it within a square array of a 200 µm diameter glycerol microdroplet array, the LMA was produced. The focal length ranged from approximately -0.96 to -0.3 mm within a voltage range of 0 to 60 Vrms. The glycerol microdroplets, characterized by their shapes, sizes, curvatures, and filling factors, can be precisely controlled by designing an OTS patterning or adjusting the dip-coating speed. This approach offers a rapid and high-throughput method for preparation. Our approach to fabricating tunable LMA offers several advantages, including simplicity of fabrication, uniform structural properties, cost-effectiveness, polarization independence, and excellent optical performance. These focus-tunable LMAs hold significant potential for applications in image processing, 3D displays, medical endoscopy, and military technologies.
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BACKGROUND: Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers with poor prognosis in the head and neck. Elucidating molecular mechanisms underlying OSCC occurrence and development is important for the therapy. Dysregulated palmitoylation-related enzymes have been reported in several cancers but OSCC. OBJECTIVES: To explore the role of palmitoyl-protein thioesterase 1 (PPT1) in OSCC. METHODS: Differentially expressed genes (DEGs) and related protein-protein interaction networks between normal oral epithelial and OSCC tissues were screened and constructed via different online databases. Tumor samples from 70 OSCC patients were evaluated for the relationship between PPT1 expression level and patients'clinic characteristics. The role of PPT1 in OSCC proliferation and metastasis was studied by functional experiments including MTT, colony formation, EdU incorporation and transwell assays. Lentivirus-based constructs were used to manipulate gene expression. FerroOrange probe and malondialdehyde assay were used to determine ferroptosis. Growth of OSCC cells in vivo was investigated by a xenograft mouse model. RESULTS: A total of 555 DEGs were obtained, and topological analysis revealed that PPT1 and GPX4 might play critical roles in OSCC. Increased PPT1 expression was found to be correlated with poor prognosis of OSCC patients. PPT1 effectively promoted the proliferation, migration and invasion while inhibited the ferroptosis of OSCC cells. PPT1 affected the expression of glutathione peroxidase 4 (GPX4). CONCLUSION: PPT1 promoted growth and inhibited ferroptosis of OSCC cells. PPT1 might be a potential target for OSCC therapy.
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Proliferação de Células , Ferroptose , Neoplasias Bucais , Tioléster Hidrolases , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Ferroptose/fisiologia , Regulação Neoplásica da Expressão Gênica , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Bucais/patologia , Neoplasias Bucais/metabolismo , Neoplasias Bucais/genética , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Tioléster Hidrolases/metabolismo , Tioléster Hidrolases/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismoRESUMO
BACKGROUND: Collagen-related cell adhesion molecules (CAMs) are a major component of the extracellular matrix (ECM) and often accumulate in the liver during chronic liver disease or hepatocellular carcinoma (HCC). In this study we identified several promising collagens related to CAMs that may be of clinical use for the diagnosis and prognosis of HCC. METHODS: We obtained multi-omics data including RNA sequencing (RNA-Seq) data, microarray data, proteomic data from the TCGA, GEO databases, GTEx, and NODE. Bioinformatics analyses were then performed to investigate correlations between the expression patterns of significant genes and HCC. Tumor tissue and para-cancerous tissue samples from HCC patients were also used to validate the results using RT-PCR. RESULTS: A literature research and LASSO-COX analysis identified three significant collagen-related CAM genes: SERPINH1, DCN, and ITGB1. Immunohistochemistry images in the Human Protein Atlas Project database showed that SERPINH1 and ITGB1 proteins were moderately or highly expressed in HCC tumor tissues compared to para-cancerous tissue, whereas DCN expression was lower in HCC tumor tissue. These results were validated by RT-PCR. Low- and high-risk groups of HCC patients were distinguished by the logistic panel in the TCGA database. These showed significantly different prognosis, clinicopathological features, and immune cell infiltration. Logistic regression was used to construct predictive models based on the individual expression levels of DCN, SERPINH1, and ITGB1. These showed highly accurate diagnostic ability (AUC = 0.987). CONCLUSIONS: The current findings suggest that the collagen-related CAMs DCN, SERPINH1, and ITGB1 may be potential therapeutic targets in HCC. Logistic panels of DCN, SERPINH1 and ITGB1 could serve as non-invasive and effective diagnostic biomarkers for HCC. CLINICAL TRIAL REGISTRATION: Identifier: NCT03189992. Registered on June 4, 2017. Retrospectively registered (https://clinicaltrials.gov/).
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Proteômica , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , ColágenoRESUMO
BACKGROUND/AIM: This research endeavor sought to distinguish small (≤ 3 cm) well-differentiated hepatocellular carcinoma (WD-HCC) from dysplastic nodules (DN) by employing traditional imaging features and mean apparent diffusion coefficient (mADC) values derived from diffusion-weighted imaging (DWI). MATERIALS AND METHODS: In this retrospective analysis, we assessed a cohort of ninety patients with confirmed dysplastic nodules (DNs) (n = 71) or well-differentiated hepatocellular carcinoma (WD-HCC) (n = 41) who had undergone dynamic contrast-enhanced magnetic resonance imaging between March 2018 and June 2021. Multivariable logistic regression analyses were executed to pinpoint characteristics that can effectively differentiate histologic grades. A region-of-interest (ROI) encompassing all lesion voxels was delineated on each slice containing the mass in the ADC map. Subsequently, the whole-lesion mean ADC (mADC) were computed from these delineations. A receiver operating characteristic (ROC) curve was generated to assess the discriminatory efficacy of the mADC values in distinguishing between WD-HCC and DN. RESULTS: Among the histopathological types from benign to malignant, mADC showed a significant decrease (P < 0.001). The mADCs were effective in distinguishing WD-HCC from DN [AUC, 0.903 (95% CI 0.849-0.958)]. The best cutoffs for the Youden index were 0.0012 mm2/s for mADC, with moderate sensitivity (70.7%) and high specificity (94.4%). MRI features including hyperintensity at arterial phase (odds ratio, 21.2; P = 0.009), mADC < 0.0012 mm2/s (odds ratio, 52.2; P < 0.001) were independent predictors for WD-HCC at multivariable analysis. The AUC value of hyperintensity at arterial phase was 0.857 (95% CI 0.786-0.928). The composite diagnostic criterion of arterial hyperintensity + mADC < 0.0012 mm2/s showed good performance [AUC, 0.926 (95% CI 0.878-0.975)], displaying increased sensitivity compared to individual assessments involving arterial hyperintensity (P = 0.013), mADC < 0.0012 mm2/s (P = 0.004), or LR-5 (P < 0.001), with similar specificity compared to LR-5 (P = 0.193). CONCLUSION: DN and WD-HCC displayed contrasting diffusion characteristics, attainable to distinguish with satisfactory accuracy. The utilization of arterial phase hyperintensity and mADC < 0.0012 on MRI facilitated the differentiation of WD-HCC from DN.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Estudos Retrospectivos , Meios de Contraste , Sensibilidade e Especificidade , Diagnóstico Diferencial , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
Objective MiRNA-766-3p has been shown to be associated with a variety of cancers. However, few studies have been done in gastric cancer (GC). This study explores the mechanism of miR-766-3p in GC. Methods The potential targets of microRNA (miRNA) were predicted using Tarbase and Targetscan databases. The results are intersected with differential genes (DEGs) (fold change > 1.5, P < 0.05) in gastric cancer to obtain potential core targets. The hub targets screened by constructing PPI networks (degree > 5, expression > 0.5). Validating the differential expression and expression in immunohistochemistry of these targets through the database. And the binding sites between miRNAs and mRNAs were verified using dual-luciferase Assay. Finally, qRT-PCR and Western Blot experiments were conducted to validate the hub targets and signal pathways. Results The potential hub targets from the PPI network were THBS2, COL1A1, FGG, FGB, and PLAU. Combining database, luciferase Assay and experimental validation, miR-766-3p can sponge COL1A1 and it plays the most important role in gastric cancer progression. In GC, COL1A1 was upregulated and the enrichment analysis revealed that COL1A1 regulates PI3K/AKT signal pathway, and AKT is also highly expressed in gastric cancer. Conclusion The miR-766-3p can inhibit the progression of gastric cancer by targeting COL1A1 and regulating the PI3K/AKT signal pathway. It could be a potential therapy option for the GC.
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BACKGROUND: Filaggrin (FLG) is an essential protein that plays a vital role in maintaining skin barrier function and moisture levels, allowing the skin to adapt to dry environments. However, the precise temporal dynamics of FLG metabolism in the human epidermis remain poorly understood, and suitable tools to study these time-dependent effects are currently lacking. OBJECTIVE: To investigate the molecular mechanisms and time course of FLG metabolism and skin barrier function under high- and low-humidity conditions, utilizing a reconstructed epidermis model. METHODS: EpiSkin specimens cultured under humid or dry conditions for varying durations (2-48 h) were compared by assessing FLG degradation and skin barrier formation using immunofluorescence staining and western blotting. RESULTS: Under conditions of low humidity, the proteolysis of FLG in EpiSkin increased between 4 and 12 h and was accompanied by elevated levels of cysteine-aspartic protease (caspase)-14. The expression of peptidyl arginine deiminase 1 and calpain 1 also increased at 4 h. However, after 24 h, the expression of these three FLG-degrading proteins significantly decreased. Conversely, the levels of pyrrolidone-5-carboxylic acid and urocanic acid initially decreased at 2 h and then increased between 12 and 24 h. Additionally, the expression of skin barrier proteins, such as FLG, transglutaminase 5, loricrin and zonula occludens-1, decreased starting from 12 h. Notably, epidermal cell viability and activity were also inhibited. CONCLUSION: We propose a reliable and ethical model to study the temporal dynamics of FLG metabolism and its role in skin barrier function. Using a commercially reconstructed epidermis to mimic dry skin formation obviates the need for animal and human testing.
CONTEXTE: la filaggrine (FLG) est une protéine essentielle qui joue un rôle vital dans le maintien de la fonction de barrière cutanée et des taux d'humidité, permettant à la peau de s'adapter aux environnements secs. Cependant, la dynamique temporelle précise du métabolisme de la FLG dans l'épiderme humain reste mal comprise, et des outils appropriés pour étudier ces effets dépendant du temps font actuellement défaut. OBJECTIF: étudier les mécanismes moléculaires et l'évolution dans le temps du métabolisme de la FLG et de la fonction de barrière cutanée en milieux à humidité élevée et faible, en utilisant un modèle d'épiderme reconstruit. MÉTHODES: les échantillons EpiSkin cultivés en milieux humides ou secs pendant des durées variables (2 à 48 h) ont été comparés en évaluant la dégradation de la FLG et la formation d'une barrière cutanée à l'aide d'une coloration par immunofluorescence et d'un Western blot. RÉSULTATS: en milieux à faible humidité, la protéolyse de la FLG dans EpiSkin a augmenté entre 4 et 12 h et s'est accompagnée de taux élevés de cystéineprotéase aspartique (caspase)14. L'expression du peptidyl arginine déiminase 1 et de la calpaïne 1 a également augmenté à 4 h. Cependant, après 24 h, l'expression de ces trois protéines de dégradation de la FLG a significativement diminué. Inversément, les taux d'acide pyrrolidone5carboxylique et d'acide urocanique ont initialement diminué au bout de 2 h, puis ont augmenté entre 12 et 24 h. En outre, l'expression des protéines de la barrière cutanée, telles que la FLG, la transglutaminase 5, la loricrine et le zonula occludens1, a diminué à partir de 12 h. Notamment, la viabilité et l'activité des cellules épidermiques ont également été inhibées. CONCLUSION: nous proposons un modèle fiable et éthique pour étudier la dynamique temporelle du métabolisme de la FLG et son rôle dans la fonction de barrière cutanée. L'utilisation d'un épiderme reconstitué commercialement pour imiter la formation d'une peau sèche élimine la nécessité de réaliser des examens sur des animaux et des humains.
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Epiderme , Proteínas Filagrinas , Umidade , Proteínas de Filamentos Intermediários , Proteínas Filagrinas/metabolismo , Humanos , Proteínas de Filamentos Intermediários/metabolismo , Epiderme/metabolismo , Modelos Biológicos , Proteólise , Caspase 14/metabolismo , Ácido Urocânico/metabolismoRESUMO
Fluorescent lateral flow immunoassay (LFA) systems are versatile tools for sensitive and quantitative detection of disease markers at the point of care. However, traditional fluorescent nanoparticle-based lateral flow immunoassays are not visible under room light, necessitate an additional fluorescent reader, and lack flexibility for different application scenarios. Herein, we report a dual-readout LFA system for the rapid and sensitive detection of C-reactive protein (CRP) in clinical samples. The system relied on the aggregation-induced emission nanobeads (AIENBs) encapsulated with red AIE luminogen, which possesses both highly fluorescent and colorimetric properties. The AIENB-based LFA in the naked-eye mode was able to qualitatively detect CRP levels as low as 8.0 mg/L, while in the fluorescent mode, it was able to quantitatively measure high-sensitivity CRP (hs-CRP) with a limit of detection of 0.16 mg/L. The AIENB-based LFA system also showed a good correlation with the clinically used immunoturbidimetric method for CRP and hs-CRP detection in human plasma. This dual-modal AIENB-based LFA system offers the convenience of colorimetric testing and highly sensitive and quantitative detection of disease biomarkers and medical diagnostics in various scenarios.
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Proteína C-Reativa , Nanopartículas , Humanos , Sistemas Automatizados de Assistência Junto ao Leito , Imunoensaio/métodos , Limite de Detecção , CorantesRESUMO
A photoinduced reductive Reformatsky reaction by cooperative dual-metal catalysis is described. This methodology enables the implementation of this venerable reaction in environmentally friendly conditions, obviating the need for a stoichiometric amount of metals. A broad range of synthetically useful ß-hydroxy esters can be efficiently prepared in moderate to high yields using this protocol.
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This research aims to investigate the impact of human work interruptions on positive affective responses and their underlying mechanisms in the Chinese context. In the first stage, this study conducted face-to-face semi-structured interviews with 29 employees representing diverse industries. The grounded theory research method was used to extract the construct of human work interruption, identify its core attributes, and capture the naturally emerging storyline of "human work interruptions - coping potential - polychronicity - positive affective responses". In the second stage, a theoretical model was constructed and validated using 362 questionnaires. The results indicate that in the Chinese context: (1) human work interruptions can trigger positive affective responses; (2) coping potential mediates the relationship between human work interruptions and positive affective responses; (3) when individuals have a higher level of polychronicity, the impact of human work interruptions on positive affective responses via coping potential is enhanced. The findings of this study effectively address the hypothesis of the "positive aspect" of work interruptions proposed by management scholars and contribute to the existing literature on work interruptions and positive affective responses. Moreover, this research provides practical and theoretical implications for managers and employees in managing and coping with human work interruptions.
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Adaptação Psicológica , Modelos Teóricos , Humanos , Inquéritos e QuestionáriosRESUMO
Background: Findings of fatty lesions in the context of other imaging manifestations, especially bone marrow edema and erosions can effectively assist in the diagnosis of axSpA. Chemical shift-encoded MRI is a sequence which allows for the quantification of fat signal and has been applied in the imaging evaluation of the SIJ in axSpA. The objective of this study was to investigate the diagnostic performance of morphological features of fatty lesions visualized by CSE-MRI in the imaging evaluation of SIJ in axSpA. Methods: Fatty lesions with morphological features (subchondral, homogeneity and distinct border) were assessed and recorded as a binary variable in each quadrant of the SIJ. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for different morphological features as well as the anatomical distribution in patients with nr-axSpA and r-axSpA. T1-weighted images and CSE-MRI fat fraction maps were directly compared in the recognition of different morphological features. Results: Eighty-two patients [non-SpA (n = 21), nr-axSpA (n = 23), r-axSpA (n = 38)] with lower back pain (LBP) were enrolled. Presence of the three morphological features of fatty lesions had a specificity of 90.48% in axSpA. The sensitivities of being subchondral, homogeneity and distinct border were 52.17, 39.13 and 39.13% in nr-axSpA on T1-weighted images. For patients with r-axSpA, the sensitivities reached 86.84, 76.32 and 57.89%. No significant difference was found in the distribution of fatty lesions between T1-weighted images and CSE-MRI. However, CSE-MRI fat fraction maps could detect significantly more fatty lesions with homogeneity (p = 0.0412) and distinct border (p = 0.0159) than T1-weighted images in the sacroiliac joint, but not subchondral lesions (p = 0.6831). Conclusion: The homogeneity and distinct border are more relevant for the diagnosis of axSpA. Moreover, CSE-MRI could detect more typical morphological features of fatty lesions than T1-weighted images in showing these two features. The presence of all three features was more likely to be indicative of axSpA.
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ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of the herbal formula Huosu-Yangwei (HSYW) in the treatment of advanced gastric cancer and chronic atrophic gastritis with precancerous lesions has been reported in clinical trials. However, the molecular mechanisms underlying its inhibition of gastric tumor are not well-understood. AIM OF THE STUDY: Combined with transcriptomics and systems network-based molecular mechanism to explore the potential circRNA-miRNA-mRNA network of HSYW in the treatment of gastric cancer. MATERIALS AND METHODS: Animal experiments were conducted to investigate the effect of HSYW on tumor growth in vivo. RNA sequencing (RNA-seq) was implemented to identify the differentially expressed (DE) genes. Predictive miRNA targets and mRNA were used to construct circRNA-miRNA-mRNA networks and protein-protein interaction (PPI) networks. Quantitative real-time PCR (qRT-PCR) was utilized to verify the accuracy of the proposed circRNA-miRNA-mRNA networks. Additionally, the differentially expressed target proteins between gastric cancer (GC) and normal patients were assessed using data from the TCGA (The Cancer Genome Atlas) and HPA (The Human Protein Atlas) databases. RESULTS: We demonstrate HSYW significantly inhibits tumor growth of N87 cell-bearing Balb/c mice. Transcriptomic analysis revealed the existence of 119 differentially expressed (DE) circRNAs and 200 DE mRNAs between HSYW-treated and model mice. By associating predicted circRNA-miRNA pairs and miRNA-mRNA pairs, we constructed a circRNA-miRNA-mRNA (CMM) network. Furthermore, a protein-protein interaction (PPI) network was developed using the differential expressed mRNAs. Consequently, the reconstructed core CMM network and qRT-PCR validation indicated that 4 circRNAs, 5 miRNAs and 6 mRNAs could potentially serve as biomarkers to assess the therapeutic effects of HSYW-treated N87-bearing Balb/c mice. The TCGA and HPA databases also demonstrated that mRNA KLF15 and PREX1 had substantial differences between gastric cancer (GC) and healthy controls. CONCLUSIONS: By combining the experimental and bioinformatics analysis, this study confirms that the circRNA_00240/hsa-miR-642a-5p/KLF15 and circRNA_07980/hsa-miR-766-3p/PREX1 pathways play critical roles in HSYW-treated gastric cancer.
Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , Camundongos , Animais , RNA Circular/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Transcriptoma , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Redes Reguladoras de GenesRESUMO
Pancreatic adenocarcinoma (PAAD) has been a huge challenge to public health due to its increasing incidence, frequent early metastasis, and poor outcome. The molecular basis of tumorigenesis and metastasis in PAAD is largely unclear. Here, we identified a novel tumor-suppressor long noncoding RNA (lncRNA) MBNL1-AS1, in PAAD and revealed its downstream mechanism. Quantitative real-time PCR (qRT-PCR) data showed that MBNL1-AS1 expression was significantly downregulated in PAAD tissues and cells, which was closely associated with metastasis and poor prognosis. Cell counting kit-8 (CCK-8) assay, transwell assay, and western blot verified that overexpression of MBNL1-AS1 suppressed cell proliferation, migration, and epithelial mesenchymal transformation (EMT) behavior in PAAD cells. By using a dual luciferase reporter gene system, we confirmed that miR-301b-3p was a direct target of MBNL1-AS1. Further mechanismic study revealed that upregulation of miR-301b-3p abolished the inhibitory effect of MBNL1-AS1 overexpression on cell proliferation, tumorigenesis, migration and EMT. Our results demonstrate that MBNL1-AS1 plays a tumor-suppressive role in PAAD mainly by downregulating miR-301b-3p, providing a novel therapeutic target for PAAD.