RESUMO
BACKGROUND: Abnormal angiogenesis is crucial for gallbladder cancer (GBC) tumor growth and invasion, highlighting the importance of elucidating the mechanisms underlying this process. LncRNA (long non-coding RNA) is widely involved in the malignancy of GBC. However, conclusive evidence confirming the correlation between lncRNAs and angiogenesis in GBC is lacking. METHODS: LncRNA sequencing was performed to identify the differentially expressed lncRNAs. RT-qPCR, western blot, FISH, and immunofluorescence were used to measure TRPM2-AS and NOTCH1 signaling pathway expression in vitro. Mouse xenograft and lung metastasis models were used to evaluate the biological function of TRPM2-AS during angiogenesis in vivo. EDU, transwell, and tube formation assays were used to detect the angiogenic ability of HUVECs. RIP, RAP, RNA pull-down, dual-luciferase reporter system, and mass spectrometry were used to confirm the interaction between TRPM2-AS, IGF2BP2, NUMB, and PABPC1. RESULTS: TRPM2-AS was upregulated in GBC tissues and was closely related to angiogenesis and poor prognosis in patients with GBC. The high expression level and stability of TRPM2-AS benefited from m6A modification, which is recognized by IGF2BP2. In terms of exerting pro-angiogenic effects, TRPM2-AS loaded with exosomes transported from GBC cells to HUVECs enhanced PABPC1-mediated NUMB expression inhibition, ultimately promoting the activation of the NOTCH1 signaling pathway. PABPC1 inhibited NUMB mRNA expression through interacting with AGO2 and promoted miR-31-5p and miR-146a-5p-mediated the degradation of NUMB mRNA. The NOTCH signaling pathway inhibitor DAPT inhibited GBC tumor angiogenesis, and TRPM2-AS knockdown enhanced this effect. CONCLUSIONS: TRPM2-AS is a novel and promising biomarker for GBC angiogenesis that promotes angiogenesis by facilitating the activation of the NOTCH1 signaling pathway. Targeting TRPM2-AS opens further opportunities for future GBC treatments.
Assuntos
Carcinoma in Situ , Neoplasias da Vesícula Biliar , MicroRNAs , RNA Longo não Codificante , Canais de Cátion TRPM , Humanos , Animais , Camundongos , Neoplasias da Vesícula Biliar/genética , RNA Longo não Codificante/genética , MicroRNAs/genética , Canais de Cátion TRPM/metabolismo , Angiogênese , Linhagem Celular Tumoral , Transdução de Sinais , RNA Mensageiro , Proliferação de Células , Receptor Notch1/metabolismo , Proteínas de Ligação a RNA/metabolismoRESUMO
BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood. METHODS: To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue. RESULTS: Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs. CONCLUSIONS: This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.
Assuntos
Neoplasias dos Ductos Biliares , Fibroblastos Associados a Câncer , Colangiocarcinoma , Regulação Neoplásica da Expressão Gênica , Análise de Célula Única , Microambiente Tumoral , Colangiocarcinoma/genética , Colangiocarcinoma/patologia , Humanos , Microambiente Tumoral/genética , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Prognóstico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/metabolismo , Transcriptoma/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Comunicação CelularRESUMO
The pathophysiology of immune thrombocytopenia (ITP) involves immune-mediated platelet destruction. The presence of adipose tissue in obese individuals creates an inflammatory environment that could potentially impact the clinical course and outcomes of ITP. However the relationship between obesity and ITP outcomes has not been well described. We evaluated ITP outcomes in 275 patients diagnosed with primary ITP from 2012 to 2022. Patients were categorized into four groups based on their body mass index (BMI) at diagnosis. Female gender was associated with a lower platelet count at the time of diagnosis at any BMI. Patients with high BMI had lower platelet counts at diagnosis and at platelet nadir (p < 0.001), an increased likelihood of requiring therapy (p < 0.001) and requiring multiple lines of therapy (p = 0.032). Non-obese patients who required corticosteroid treatment experienced a longer remission duration compared to obese patients (p = 0.009) and were less likely to be steroid-dependent (p = 0.048). Our findings suggest that obesity may be a significant risk factor for developing ITP and for ITP prognosis. Future studies are needed to evaluate the role of weight loss intervention in improving ITP outcomes.
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Índice de Massa Corporal , Obesidade , Púrpura Trombocitopênica Idiopática , Humanos , Feminino , Masculino , Púrpura Trombocitopênica Idiopática/terapia , Púrpura Trombocitopênica Idiopática/sangue , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Obesidade/complicações , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Idoso , Contagem de Plaquetas , Fatores de Risco , Prognóstico , Corticosteroides/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVES: To develop and validate a deep learning-based model for predicting 12-month axial length (AL) elongation using baseline factors and early corneal topographic changes in children treated with orthokeratology (Ortho-K) and to investigate the association between these factors and myopia control impact. METHODS: A total of 115 patients with Ortho-K were enrolled. Influential baseline factors that have a statistically significant correlation with 12-month AL from medical records were selected using Pearson correlation coefficients. Simultaneously, the height, area, and volume of the defocus region were directly calculated from the corneal topography. Then, the prediction model was developed by combining multiple linear regression and deep neural network and evaluated in an independent group (83 patients for developing the algorithm and 32 patients for evaluation). RESULTS: Age ( r= -0.30, P <0.001), spherical equivalent refractive (SE; r =0.20, P =0.032), and sex ( r =0.19, P =0.032) were significantly correlated with the AL elongation while pupil diameter, flat k, steep k, horizontal corneal diameter (white to white), anterior chamber depth, and cell density were not ( P >0.1). The prediction model was developed using age, SE, and corneal topographic variation, and the validation of the model demonstrated its effectiveness in predicting AL elongation. CONCLUSIONS: The AL elongation was accurately predicted by the deep learning model, which effectively incorporated both baseline factors and corneal topographic variation.
Assuntos
Aprendizado Profundo , Miopia , Procedimentos Ortoceratológicos , Criança , Humanos , Comprimento Axial do Olho , Miopia/terapia , Topografia da Córnea , Refração Ocular , Estudos RetrospectivosRESUMO
BACKGROUND: To evaluate the relationship between amount of corneal refractive change (CRC) after wearing orthokeratology (Ortho-K) lenses and axial length (AL) growth. METHODS: We retrospectively enrolled 77 patients (77 eyes) aged 8-14 years who wore Ortho-K lenses more than 12 months. We divided the patients into 2 subgroups: spherical equivalent (SE) ≤ -3.0 D and SE > -3.0 D subgroup. The sagittal and tangential curvature maps and corneal topographic data within the 8-mm diameter ring at the baseline and during follow-up visits after wearing Ortho-K lens were recorded in addition to the area, height, and volume of the CRC region. The AL data were recorded at the baseline and during follow-up visits. Multivariate linear regression was conducted to analyze associations between the area, height, and volume of the CRC region, AL elongation, and SE. RESULTS: The average change in the CRC region was 9.77 ± 0.60 D in height, 16.66 ± 3.61 mm2 in area, and 87.47 ± 8.96 D*mm2 in volume on the tangential diagram after wearing Ortho-K lenses for 3 months. The AL showed a change of 0.19 ± 0.14 mm after 1 year of Ortho-K lens wear (P < 0.05). At 1 year, AL elongation was negatively correlated with the area (P = 0.019) and volume (P < 0.001) of the CRC region. At 1 year, for every 1-mm2 increase in the area and every 1-D*mm2 increase in the volume of the CRC region, the average AL elongation decreased by 0.01 mm and 0.002 mm, respectively, in the multivariate analysis. In patients with SE ≤ -3.0 D, AL elongation was negatively correlated with the CRC-region volume (ß = -0.002, P = 0.018), and in patients with SE > -3.0 D, AL elongation was negatively correlated with the CRC-region area (ß = -0.017, P = 0.016). CONCLUSIONS: The AL elongation-control efficacy of Ortho-K lenses may be related to the area and volume of the CRC region.
Assuntos
Miopia , Procedimentos Ortoceratológicos , Humanos , Estudos Retrospectivos , Córnea , Miopia/terapia , Refração Ocular , Topografia da Córnea , Comprimento Axial do OlhoRESUMO
Endometrial cancer has the highest incidence of uterine corpus cancer, the sixth most typical cancer in women until 2020. High recurrence rate and frequent adverse events were reported in either standard chemotherapy or combined therapy. Hence, developing precise diagnostic and prognostic approaches for endometrial cancer was on demand. Four hypoxia-related genes were screened for the EC prognostic model by the univariate, LASSO, and multivariate Cox regression analysis from the TCGA dataset. QT-PCR and functional annotation analysis were performed. Associations between predicted risk and immunotherapy and chemotherapy responses were investigated by evaluating expressions of immune checkpoint inhibitors, infiltrated immune cells, m6a regulators, and drug sensitivity. The ROC curve and calibration plot indicated a fair predictability of our prognostic nomogram model. NR3C1 amplification, along with IL-6 and SRPX suppressions, were detected in tumor. High stromal score and enriched infiltrated aDCs and B cells in the high-risk group supported the hypothesis of immune-deserted tumor. Hypoxia-related molecular subtypes of EC were then identified via the gene signature. Cluster 2 patients showed a significant sensitivity to Vinblastine. In summary, our hypoxia signature model accurately predicted the survival outcome of EC patients and assessed translational and transcriptional dysregulations to explore targets for precise medical treatment.
Assuntos
Neoplasias do Endométrio , Hipóxia , Feminino , Humanos , Neoplasias do Endométrio/genética , Hipóxia/genética , Nomogramas , PrognósticoRESUMO
BACKGROUND: This study aimed to compare the changes in the axial length (AL) in myopic children that wear centered and decentered orthokeratology (Ortho-K). METHODS: This retrospective study included 217 subjects who were treated with an Ortho-K lens for >12 months. The subjects were divided into three groups based on the magnitude of the Ortho-K lens treatment zone decentration: mildly, moderately, and severely decentered groups. Distance and direction of treatment zone decentration were calculated using software that was developed in-house. The AL changes in different groups were compared. RESULTS: Based on the distance of the treatment zone decentration, 65 children (65 eyes) were included in the mildly decentered group, 114 children (114 eyes) in the moderately decentered group, and 38 children (38 eyes) in the severely decentered group. The mean decentration distance in the three groups was 0.35 ± 0.11 mm, 0.71 ± 0.13 mm, and 1.21 ± 0.22 mm, respectively. The mean AL increase in the three groups after 12 months of Ortho-K lens wear was 0.24 ± 0.21 mm, 0.23 ± 0.18 mm, and 0.19 ± 0.20 mm, respectively. There were no significant differences in AL changes among the three groups. CONCLUSIONS: Ortho-K lens decentration is common in clinical practice. The AL change after Ortho-K lens wear was not significantly different in subjects with different magnitudes of Ortho-K lens decentration. Fitting the Ortho-K lens in the properly centered zone is recommended to ensure the safety of Ortho-K lens wear and to maintain visual quality.
Assuntos
Lentes de Contato , Miopia , Procedimentos Ortoceratológicos , Criança , Córnea , Topografia da Córnea , Humanos , Miopia/terapia , Refração Ocular , Estudos RetrospectivosRESUMO
The distribution patterns and health risk assessment of nitrated polycyclic aromatic hydrocarbons (NPAHs), hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), and regular 16 priority polycyclic aromatic hydrocarbons (PAHs) in sediment from the Songhua River in northeastern China were investigated in this research. During dry seasons, concentrations of 16 USEPA priority PAHs, OH-PAHs, and NPAHs were extremely high, with average values of 1220 ± 288, 317 ± 641, 2.54 ± 3.98, and 12.2 ± 22.1 ng/g (dry weight, dw). The dry period level was confirmed to be 4 times greater than the wet period concentration. Modeling with positive matrix factorization (PMF) and estimation of diagnostic isomeric ratios were applied for identifying sources, according to the positive matrix factorization model: vehicle emissions (38.1%), biomass burning (25%), petroleum source (23.4%), and diesel engines source (13.5%) in wet season as well as wood combustion (44.1%), vehicle source (40.2%), coke oven (10.8%), and biomass burning (4.9%) in the dry season. The greatest seasonal variability was attributed to high molecular weight compounds (HMW PAHs). BaP was confirmed to be 81% carcinogenic in this study, which offers convincing proof of the escalating health issues.
Assuntos
Coque , Petróleo , Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/análise , Rios , Emissões de Veículos/análise , Monitoramento Ambiental , Nitratos/análise , China , Medição de RiscoRESUMO
PURPOSE: microRNA-128 (miR-128), a brain-enriched microRNA, has been reported to play a crucial role in the treatment of diseases. The c-Jun N-terminal kinase (JNK) signaling pathway exerts various biological functions such as regulation of cell proliferation, differentiation and apoptosis. In this study, we investigated the role of the miRNA-128-JNK signaling pathway in proliferation, apoptosis and autophagy of porcine adipose-derived stem cells (ASCs). METHODS: After over-expressing miR-128 in porcine ASCs, cell proliferation was determined by 2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide (XTT) method, cell apoptosis was observed by Flow cytometry (FCM), the expression of miR-128, B-cell lymphoma 2 (Bcl-2), and Bcl-2-associated X protein (Bax) was measured by RNA preparation and reverse transcription polymerase chain reaction (RT-PCR), and protein expression of JNK, phosphorylated JNK (p-JNK) and LC3B was analyzed by Western Blot analysis. RESULTS: The over-expression of miR-128 potently promoted cell proliferation and autophagy while suppressed the apoptosis of porcine ASCs. In addition, the down-regulated expression level of p-JNK was detected in miR-128-over-expressed porcine ASCs. However, followed by the block of the JNK signaling pathway using SP600125 inhibitor, the effects of miR-128 on the proliferation, apoptosis and autophagy of porcine ASCs were significantly suppressed. CONCLUSION: It is demonstrated that the miR-128-JNK signaling pathway is a potential therapeutic target for the treatment of obesity.
Assuntos
Proliferação de Células/genética , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , Animais , Antracenos/farmacologia , Apoptose/genética , Autofagia/genética , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/genética , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais/genética , SuínosRESUMO
ABSTRACT: Although most studies have shown the psychological strains associated with increased risk of suicidal behaviors, how psychological strains are linked to suicidal behaviors is still unclear. The current study examines the possible mediation effect of psychological distress and hopelessness on the relationship between psychological strains and suicidal behaviors among Chinese medical college students. A cross-sectional survey was conducted from November 2017 to March 2018 involving 5703 medical college students, and the 12-month prevalence of suicidal behaviors was 12.89%. Psychological strains significantly associated with suicidal behaviors, and psychological distress and hopelessness partially explained this relationship. A positive psychological intervention program is needed to buffer the psychological strains, which is a crucial predictor for suicidal behaviors among Chinese medical college students.
Assuntos
Esperança , Angústia Psicológica , Estresse Psicológico/psicologia , Estudantes de Medicina/psicologia , Adulto , China , Estudos Transversais , Feminino , Humanos , Masculino , Prevalência , Adulto JovemRESUMO
BACKGROUND: The prevalence of infertility in China is high, but the advent of assisted reproduction technology (ART) has greatly eased this situation. Social media, such as WeChat official accounts, have become the preferred tool for ART centers to communicate with patients, but their attention and operational status differ, and the Internet influence of WeChat official accounts is insufficient. In addition, questions about whether Internet influence is consistent with academic influence and whether the Internet can influence patients' choice of medical treatment to a certain extent have not been explored. OBJECTIVE: This study aimed to examine the operational status and Internet influence of WeChat official accounts for ART centers and to explore the degree of Internet influence on patients' choices of medical treatment. METHODS: We collected information from the WeChat official accounts for ART centers approved by the National Health Commission of the People's Republic of China and used the technique for order of preference by similarity to ideal solution to build an Internet influence model of the ART centers and obtained a Ranking of Internet Influence on Reproductive Centers (RIIRC) for each center. RESULTS: We found there were 451 ART centers throughout the country by the end of 2016 and 498 by the end of 2018. The number of medical institutions is quite large, but their distribution is uneven, and their level of medical technical ability is very different. Analysis of the text data of posts of WeChat official accounts showed the ART centers have insufficient awareness of network exposure and publicity, and the RIIRC of some medical institutions was inconsistent with their medical level and academic status. CONCLUSIONS: ART institutions have varying degrees of emphasis and use of WeChat official accounts in China. They fail to realize that the Internet influence of WeChat may bring them potential patient resources and that Internet influence may affect the future market structure of ART and may also potentially affect academic rankings.
Assuntos
Internet/instrumentação , Técnicas de Reprodução Assistida/tendências , Adulto , China , Feminino , Humanos , Masculino , Pesquisa Qualitativa , Mídias SociaisRESUMO
Endothelial dysfunction (ED) is an important contributor to atherosclerotic cardiovascular disease. Our previous study demonstrated that sphingomyelin synthase 2 (SMS2) promotes ED. Moreover, endoplasmic reticulum (ER) stress can lead to ED. However, whether there is a correlation between SMS2 and ER stress is unclear. To examine their correlation and determine the detailed mechanism of this process, we constructed a human umbilical vein endothelial cell (HUVEC) model with SMS2 overexpression. These cells were treated with 4-PBA or simvastatin and with LiCl and salinomycin alone. The results showed that SMS2 can promote the phosphorylation of lipoprotein receptor-related protein 6 (LRP6) and activate the Wnt/ß-catenin pathway and that activation or inhibition of the Wnt/ß-catenin pathway can induce or block ER stress, respectively. However, inhibition of ER stress by 4-PBA can decrease ER stress and ED. Furthermore, when the biosynthesis of cholesterol is inhibited by simvastatin, the reduction in intracellular cholesterol coincides with a decrease in ER stress and ED. Collectively, our results demonstrate that SMS2 can activate the Wnt/ß-catenin pathway and promote intracellular cholesterol accumulation, both of which can contribute to the induction of ER stress and finally lead to ED.
Assuntos
Estresse do Retículo Endoplasmático , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Transferases (Outros Grupos de Fosfato Substituídos)/metabolismo , Biomarcadores , Adesão Celular/efeitos dos fármacos , Células Cultivadas , Endotélio Vascular/fisiopatologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Fosforilação , Sinvastatina/farmacologia , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Via de Sinalização Wnt , beta Catenina/metabolismoRESUMO
This study was designed to investigate the protective effect of resveratrol (RES) on premature ovarian failure (POF) and the proliferation of female germline stem cells (FGSCs) at the tissue and cell levels. POF mice were lavaged with RES, and POF ovaries were co-cultured with RES and/or GANT61 in vitro. FGSCs were pretreated with Busulfan and RES and/or GANT61 and co-cultured with M1 macrophages, which were pretreated with RES. The weights of mice and their ovaries, as well as their follicle number, were measured. Ovarian function, antioxidative stress, inflammation, and FGSCs survival were evaluated. RES significantly increased the weights of POF mice and their ovaries as well as the number of follicles, while it decreased the atresia rate of follicles. Higher levels of Mvh, Oct4, SOD2, GPx, and CAT were detected after treatment with RES in vivo and in vitro. RES treatment resulted in significantly lower TNF-α and IL-6 concentrations and an obviously higher IL-10 concentration in the ovaries. In FGSCs, higher Mvh, Oct4, and SOD2 concentrations and lower TNF-α, IL-6, and MDA concentrations were measured in the RES group. Blockage of the Hh signaling pathway reversed the protective effect of RES on FGSCs. In conclusion, RES effectively improved the ovarian function of the POF model and the productive capacity of FGSCs via relieving oxidative stress and inflammation and a mechanism involving the Hh signaling pathway, suggesting that RES is a potential agent against POF and can aid in the survival of FGSCs.
Assuntos
Antioxidantes/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Células-Tronco de Oogônios/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Insuficiência Ovariana Primária/tratamento farmacológico , Resveratrol/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Bussulfano/toxicidade , Catalase/genética , Catalase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Técnicas de Cocultura , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Feminino , Glutationa Peroxidase/genética , Glutationa Peroxidase/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Células-Tronco de Oogônios/metabolismo , Células-Tronco de Oogônios/patologia , Tamanho do Órgão/efeitos dos fármacos , Folículo Ovariano/metabolismo , Folículo Ovariano/patologia , Cultura Primária de Células , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/patologia , Piridinas/antagonistas & inibidores , Piridinas/farmacologia , Pirimidinas/antagonistas & inibidores , Pirimidinas/farmacologia , Transdução de Sinais , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Glutationa Peroxidase GPX1RESUMO
Atherosclerosis is the pathological basis of cardiovascular disease, whilst endothelial dysfunction (ED) plays a primary role in the occurrence and development of atherosclerosis. Simvastatin has been shown to possess significant anti-atherosclerosis activity. In this study, we evaluated the protective effect of simvastatin on endothelial cells under oxidative stress and elucidated its underlying mechanisms. Simvastatin was found to attenuate H2O2-induced human umbilical vein endothelial cells (HUVECs) dysfunction and inhibit the Wnt/ß-catenin pathway; however, when this pathway was activated by lithium chloride, endothelial dysfunction was clearly enhanced. Further investigation revealed that simvastatin did not alter the expression or phosphorylation of LRP6, but reduced intracellular cholesterol deposition and inhibited endoplasmic reticulum (ER) stress. Inducing ER stress with tunicamycin activated the Wnt/ß-catenin pathway, whereas reducing ER stress with 4-phenylbutyric acid inhibited it. We hypothesize that simvastatin does not affect transmembrane signal transduction in the Wnt/ß-catenin pathway, but inhibits ER stress by reducing intracellular cholesterol accumulation, which blocks intracellular signal transduction in the Wnt/ß-catenin pathway and ameliorates endothelial dysfunction.
Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Peróxido de Hidrogênio/toxicidade , Sinvastatina/farmacologia , Adesão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Colesterol/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Modelos Biológicos , Estresse Oxidativo/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate the expression and biological function of limb-bud and heart development (LBH) in prostate cancer. METHODS: Using real-time quantitative polymerase chain reaction (RT-qPCR), Western blot and immunohistochemistry, we detected the expression of LBH in the prostate cancer and adjacent normal tissues of 20 prostate cancer patients. We transfected the PC-3 and LNCaP cells with siRNA-1, siRNA-2 or negative control siRNA to silence the expression of LBH, and then observed the proliferation, immigration and invasiveness of the cells by CCK-8 and Transwell assays. RESULTS: The expression of LBH mRNA was significantly higher in the prostate cancer than in the normal tissue (4.8 ± 2.4 vs 1.8 ± 1.1, P = 0.032), and so was that of the LBH protein (3.5 ± 1.2 vs 1.3 ± 0.6, P = 0.019) and the positive rate of LBH expression was (90% ï¼»18/20ï¼½ vs 15% ï¼»3/20ï¼½, P = 0.006). Interfering with the LBH expression significantly reduced the proliferation of both the PC-3 and LNCaP cells, with a remarkable decrease at 96 hours in the A450 value of the PC-3 cells transfected with siRNA-1 (1.2 ± 0.1) and siRNA-2 (1.1 ± 0.1) as compared with that in the negative control group (1.8 ± 0.2) (P < 0.01) as well as in the A450 value of the LNCaP cells (1.4 ± 0.2 and 1.1 ± 0.2 vs 1.9 ± 0.2, P < 0.01). The count of the PC-3 cells that migrated through the polycarbonate membrane was significantly lower in the siRNA-1 and siRNA-2 transfection groups than in the negative control (55.5 ± 6.4 and 44.9 ± 4.5 vs 175.6 ± 25.8, P < 0.05), and so was that of the LNCaP cells (46.4 ± 5.8 and 40.2 ± 8.2 vs 125.3 ± 13.5, P < 0.05). Cell invasion assay also showed significant lower number of the PC-3 cells penetrating the polycarbonate membrane and matrigel in the siRNA-1 and siRNA-2 transfection groups than in the negative control (82.5 ± 7.5 and 68.4 ± 5.5 vs 138.2 ± 10.7, P < 0.05) as well as in that of the LNCaP cells (46.4 ± 5.8 and 23.1 ± 6.2 vs 92.1 ± 10.5, P < 0.05). CONCLUSIONS: The overexpression of LBH may play an important role in the development and progression of prostate cancer and serve as a therapeutic target in the treatment of the malignance.
Assuntos
Regulação Neoplásica da Expressão Gênica , Coração , Botões de Extremidades , Neoplasias da Próstata , Linhagem Celular Tumoral , Movimento Celular , Perfilação da Expressão Gênica , Coração/embriologia , Humanos , Botões de Extremidades/embriologia , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/fisiopatologia , RNA Interferente Pequeno/genética , TransfecçãoRESUMO
Crystalline ß-FeSi2 nanocubes with two {100} facets and four {011} lateral facets synthesized by spontaneous one-step chemical vapor deposition exhibit strong room-temperature ferromagnetism with saturation magnetization of 15 emu/g. The room-temperature ferromagnetism is observed from the ß-FeSi2 nanocubes larger than 150 nm with both the {100} and {011} facets. The ferromagnetism is tentatively explained with a simplified model including both the itinerant electrons in surface states and the local moments on Fe atoms near the surfaces. The work demonstrates the transformation from a nonmagnetic semiconductor to a magnetic one by exposing specific facets and the room-temperature ferromagnetism can be manipulated under light irradiation. The semiconducting ß-FeSi2 nanocubes may have large potential in silicon-based spintronic applications.
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Major adverse cardiovascular events (MACE) encompass pivotal cardiovascular outcomes such as myocardial infarction, unstable angina, and cardiovascular-related mortality. Patients undergoing peritoneal dialysis (PD) exhibit specific cardiovascular risk factors during the treatment, which can escalate the likelihood of cardiovascular events. Hence, the prediction and key factor analysis of MACE have assumed paramount significance for peritoneal dialysis patients. Current pathological methodologies for prognosis prediction are not only costly but also cumbersome in effectively processing electronic health records (EHRs) data with high dimensionality, heterogeneity, and time series. Therefore in this study, we propose the CVEformer, an attention-based neural network designed to predict MACE and analyze risk factors. CVEformer leverages the self-attention mechanism to capture temporal correlations among time series variables, allowing for weighted integration of variables and estimation of the probability of MACE. CVEformer first captures the correlations among heterogeneous variables through attention scores. Then, it analyzes the correlations within the time series data to identify key risk variables and predict the probability of MACE. When trained and evaluated on data from a large cohort of peritoneal dialysis patients across multiple centers, CVEformer outperforms existing models in terms of predictive performance.
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Aprendizado Profundo , Infarto do Miocárdio , Diálise Peritoneal , Humanos , Diálise Peritoneal/efeitos adversos , Fatores de Risco , PrognósticoRESUMO
Background: Occupational commitment (OC) is a multidimensional construct that predicts turnover intentions. The interindividual variability of nurses' OC merits further exploration. Therefore, this study aims to examine patterns of OC and its relationship with psychological empowerment and job crafting in nurses. Methods: A sample of 1,061 nurses was recruited from February 2022 to April 2022 by using a stratified four-stage cluster sampling procedure. A self-report survey included the Psychological Empowerment Scale, Job Crafting Scale, and Occupational Commitment Scale. Latent profile analysis (LPA) was used to examine the patterns of OC. Associations of the latent class membership with individual characteristics, psychological empowerment and job crafting were examined using multinomial logistic regression. Results: Three patterns of OC were identified: (1) "Low OC group" (n = 224, 21.1%); (2) "Moderate OC group" (n = 665, 62.7%); (3) "High OC group" (n = 172, 16.2%). Nurses with higher education, fewer years of service, working in medicine, lower psychological empowerment and lower job crafting had a higher likelihood of belonging to Class 1 (Low OC group). In contrast, nurses working in emergency and with higher psychological empowerment and job crafting were more likely to belong to Class 3 (High OC group). Conclusion: The findings revealed the heterogeneity of occupational commitment among nurses in China and could guide the identification and early intervention of nurses with low level of occupational commitment.
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INTRODUCTION: Art therapy (AT) has been widely utilized as a therapeutic approach for clinical nurses. In recent years, more and more researchers have applied art therapy to enhance clinical nurses' mental well-being. However, many studies conducted in this area have suffered from limited sample sizes and insufficient research evidence. AIM: This study aims to conduct a systematic evaluation of the efficacy of art therapy on the mental health of clinical nurses. METHODS: RCTs on art therapy for clinical nurses were searched across databases such as PubMed, Embase, etc., the results were analysed using RevMan 5.3. RESULTS: There were 19 RCTs encompassing 1338 clinical nurses involved in this analysis. The Meta-analysis revealed that art therapy exhibited a significant reduction in anxiety levels (measured by the SAS) among clinical nurses, as well as depression levels and perceived stress levels (measured by the CPSS). Furthermore, art therapy demonstrated a reduction in negative coping style and an improvement in positive coping style. DISCUSSION: Findings indicate that art therapy can reduce anxiety, depression and stress levels in clinical nurses, while also enhance positive coping styles and promote mental well-being. Therefore, the widespread implementation of art therapy in this context is highly recommended. DECLARATION: I hereby declare that my article is directly relevant to the field of mental health nursing. It highlights the critical importance of psychological well-being and supplements the evidence on The effects of art therapy on the occupational mental health of clinical nurses.
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Arteterapia , Humanos , Ansiedade , Estresse Psicológico , Depressão/terapia , Enfermagem Psiquiátrica , Recursos Humanos de Enfermagem HospitalarRESUMO
Renal angiomyolipoma has two histological variants: classical and epithelioid. Epithelioid angiomyolipoma is considered as a potential malignant tumor, often leading to recurrence and metastasis, with rapid progression in most of the cases. The lung is one of the most commonly reported sites of metastasis, and pulmonary metastasis of renal angiomyolipoma is usually diagnostic by computed tomography (CT) scans. Here, we report for the first time renal angiomyolipoma with lung metastasis by combining CT and magnetic resonance imaging (MRI).