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Emerging evidence shows that rheumatoid arthritis (RA) progression can be induced by the activation of Toll-like receptor (TLR) signaling pathway. Regulator of G-protein signaling 1 (RGS1) is observed to be a candidate biomarker for arthritis. Accordingly, the present study aims to determine the potential effects of RGS1 mediating TLR on RA. A rat model of collagen-induced arthritis (CIA) was established to mimic the features of RA by injection of bovine type II collagen. The rats with CIA were treated with short hairpin RNA (shRNA) against RGS1 or TLR pathway activator Poly I:C to elucidate the role of RGS1 in RA progression. The inflammatory factors were measured, and the thoracic gland and spleen indexes as well as the vascular density were determined. The expression levels of RGS1, TLR3, vascular endothelial growth factor (VEGF), metalloproteinase-2 (MMP-2), MMP-9, and interleukin 1 receptor-associated kinase-4 (IRAK4) were determined. RGS1 was robustly increased in RA. The TLR signaling pathway was suppressed by RGS1 silencing. shRNA-mediated depletion of RGS1 was shown to significantly enhance thoracic gland index and inhibit the serum levels of TNF-α, IL-1ß, and IL-17, spleen index, vascular density, and the expression levels of TLR3, VEGF, MMP-2, MMP-9, and IRAK4. However, when the rats with CIA were treated with Poly I:C, the trend of effects was opposite. These findings highlight that functional suppression of RGS1 inhibits the inflammatory response and angiogenesis by inactivating the TLR signaling pathway in rats with CIA, thereby providing a novel therapeutic target for RA treatment.
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Artritis Reumatoide/genética , Neovascularización Patológica/genética , Proteínas RGS/genética , Receptores Toll-Like/efectos de los fármacos , Animales , Artritis Experimental/tratamiento farmacológico , Artritis Reumatoide/tratamiento farmacológico , Células Cultivadas , Colágeno Tipo II/metabolismo , Fibroblastos/metabolismo , Humanos , Metaloproteinasa 2 de la Matriz/metabolismo , Neovascularización Patológica/tratamiento farmacológico , Ratas Wistar , Receptores Toll-Like/metabolismoRESUMEN
Complex RNA-RNA interactions underlie fundamental biological processes. However, a large number of RNA-RNA interactions remain unknown. Most existing methods used to map RNA-RNA interactions are based on proximity ligation, but these strategies also capture a huge amount of intramolecular RNA secondary structures, making it almost impossible to detect most RNA-RNA interactions. To overcome this limitation, we developed an efficient, genome-wide method, Capture Interacting RNA and Deep Sequencing (CIRDES) for in vivo capturing of the RNA interactome. We designed multiple 20-nt CIRDES probes tiling the whole RNA sequence of interest. This strategy obtained high selectivity and low background noise proved by qRT-PCR data. CIRDES enriched target RNA and its interacting RNAs from cells crosslinked by formaldehyde in high efficiency. After hybridization and purification, the captured RNAs were converted to the cDNA library after a highly efficient ligation to a 3' end infrared-dye-conjugated RNA adapter based on adapter ligation library construction. Using CIRDES, we detected highly abundant known interacting RNA, as well as a large number of novel targets of U6 snRNA. The enrichment of U4 snRNA, which interacts with U6, confirmed the robustness of the identification of the RNA-RNA interaction by CIRDES. These results suggest that the CIRDES is an efficient strategy for genome-wide RNA-RNA interactome analysis.
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Genoma , Sondas ARN/metabolismo , ARN Nuclear Pequeño/metabolismo , Biblioteca de Genes , Células Hep G2 , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Hibridación de Ácido Nucleico , Sondas ARN/genética , ARN Nuclear Pequeño/genética , ARN Nuclear Pequeño/aislamiento & purificación , Análisis de Secuencia de ARNRESUMEN
Several studies have shown that long non-coding RNAs (lncRNAs) may play an essential role in Epithelial-Mesenchymal Transition (EMT), which is an important step in tumor metastasis; however, little is known about the global change of lncRNA transcriptome during EMT. To investigate how lncRNA transcriptome alterations contribute to EMT progression regulation, we deep-sequenced the whole-transcriptome of MCF10A as the cells underwent TGF-ß-induced EMT. RESULTS: Deep-sequencing results showed that the long RNA transcriptome of MCF10A had undergone global changes as early as 8h after treatment with TGF-ß. The expression of 3403 known and novel lncRNAs, and 570 known and novel circRNAs were altered during EMT. To identify the key lncRNA-regulator, we constructed the co-expression network and found all junction nodes in the network are lncRNAs. One junction node, RP6-65G23.5, was further verified as a key regulator of EMT. Intriguingly, we identified 216 clusters containing lncRNAs which were located in "gene desert" regions. The expressions of all lncRNAs in these clusters changed concurrently during EMT, strongly suggesting that these clusters might play important roles in EMT. Our study reveals a global reprogramming of lncRNAs transcriptome during EMT and provides clues for the future study of the molecular mechanism of EMT.
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Neoplasias de la Mama/genética , Transición Epitelial-Mesenquimal/genética , Secuenciación de Nucleótidos de Alto Rendimiento , ARN Largo no Codificante/biosíntesis , Neoplasias de la Mama/patología , Línea Celular Tumoral , Reprogramación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Metástasis de la Neoplasia , ARN Largo no Codificante/genética , Transcriptoma/genéticaAsunto(s)
Rastreo Celular , Indoles/química , Coloración y Etiquetado , Animales , Humanos , Ratones , Especificidad de la EspecieRESUMEN
In the mangrove growth area, the availability of high-quality optical images is limited throughout the year due to cloud cover, precipitation, and sensor revisiting cycles. In the worst-case scenario, severe conditions may lead to the unavailability of, causing variations in monitoring times for mangroves across different years. This significantly impacts the accuracy of long-term sequence monitoring of mangrove dynamics. To monitor long-term dynamic changes in mangrove spatial distribution, area, and ecology we reconstructed comprehensive time series images from 2000 to 2020 based on Landsat, Sentinel-2, and moderate-resolution imaging spectroradiometer (MODIS) images. We employed neighborhood-similar pixel interpolator (NSPI) strip filling, Fmask and temporal NSPI cloud-removal and filling, and FSDAF model to monitor the long-term dynamic changes in mangrove spatial distribution, area, and ecology. All three methods effectively reconstructed the images, with the FSDAF model exhibiting the greatest accuracy. The reconstructed images suggested that the mangroves demonstrated an overall growth trend from 2000 to 2020, with an increase from 3796.74 ha to 7676.89 ha, an increase of approximately 3880.15 ha over 20 years. Despite this growth, the number of patches gradually increased, the degree of fragmentation consistently worsened, and the landscape shape gradually became irregular. The study area demonstrated pronounced overall heterogeneity, with a gradually increase in the degree of dispersion, indicating evident overall instability. Additionally, the centroid of the mangroves moved towards the ocean, which complicated their growth environment and posed a serious threat to their growth and recovery. Anthropogenic disturbance is the main factor driving changes in mangrove areas. Driving factors that affected the change in mangrove areas were ranked as follows: GDP > highway mileage > population density > precipitation > humidity > wind speed > sunshine > temperature. The results of this study provide comprehensive data for the protection and restoration of mangroves.
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BACKGROUND: Metastatic prostate cancer is a leading cause of cancer-related death in men. Cancer stem cells (CSCs) are involved in tumor progression and metastasis, including in prostate cancer. There is an obvious and urgent need for effective cancer stem cells specific therapies in metastatic prostate cancer. MicroRNAs (miRNAs) are an important class of pervasive genes that are involved in a variety of biological functions, especially in cancer. The goal of this study was to identify miRNAs involved in prostate cancer metastasis and cancer stem cells. METHODS: A microarray and qRT-PCR were performed to investigate the miRNA expression profiles in PC-3 sphere cells and adherent cells. A transwell assay was used to evaluate the migration of PC-3 sphere cells and adherent cells. MiR-143 was silenced with antisense oligonucleotides in PC-3, PC-3-M and LNCaP cells. The role of miR-143 in prostate cancer metastasis was measured by wound-healing and transwell assays in vitro and bioluminescence imaging in vivo. Bioinformatics and luciferase report assays were used to identify the target of miR-143. RESULTS: The expression of miR-143 and the migration capability were reduced in PC-3 sphere cells and progressively increased during sphere re-adherent culture. Moreover, the down-regulation of miR-143 suppressed prostate cancer cells migration and invasion in vitro and systemically inhibited metastasis in vivo. Fibronectin type III domain containing 3B (FNDC3B), which regulates cell motility, was identified as a target of miR-143. The inhibition of miR-143 increased the expression of FNDC3B protein but not FNDC3B mRNA in vitro and vivo. CONCLUSIONS: These data demonstrate for the first time that miR-143 was up-regulated during the differentiation of prostate cancer stem cells and promoted prostate cancer metastasis by repressing FNDC3B expression. This sheds a new insight into the post-transcriptional regulation of cancer stem cells differentiation by miRNAs, a potential approach for the treatment of prostate cancer.
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Fibronectinas/metabolismo , MicroARNs/fisiología , Proteínas de Neoplasias/metabolismo , Células Madre Neoplásicas/fisiología , Neoplasias de la Próstata/metabolismo , ARN Neoplásico/fisiología , Diferenciación Celular/fisiología , Línea Celular Tumoral , Movimiento Celular/fisiología , Humanos , Masculino , Análisis por Micromatrices , Neoplasias de la Próstata/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba , Cicatrización de Heridas/fisiologíaRESUMEN
Background: Severe posttraumatic stress disorder (PTSD) may lead to non-suicidal self-injury (NSSI), and borderline personality disorder (BPD) tendencies may play a role in this process. Secondary vocational students experience more social, familial and other pressures and are more vulnerable to psychological problems. Thus, we explored the effect of BPD tendencies and subjective well-being (SWB) on NSSI in secondary vocational students with PTSD. Methods: A total of 2,160 Chinese secondary vocational students in Wuhan participated in our cross-sectional investigation. The Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), criteria for PTSD, NSSI Questionnaire, Personality Diagnostic Questionnaire-4+, subjective well-being scale, and family adaptation, partnership, growth, affection, and resolve (APGAR) Index were used. We conducted a binary logistic regression model and linear regression analysis. Results: Sex (odds ratio [OR] = 0.354, 95% confidence interval [CI] = 0.171-0.733), BPD tendencies (OR = 1.192, 95% CI = 1.066-1.333) and SWB (OR = 0.652, 95% CI = 0.516-0.824) were independent factors that predicted NSSI in secondary vocational students with PTSD. Spearman's correlation analysis showed that BPD tendencies were positively correlated with NSSI frequency (r = 0.282, P < 0.01). SWB was negatively correlated with NSSI frequency (r = -0.301, P < 0.01). The linear regression showed that BPD tendencies (ß = 0.137, P < 0.05 and ß = -0.230, P < 0.001) were significantly correlated with NSSI frequency. Spearman's correlation analysis showed that family functioning was positively correlated with SWB (r = 0.486, P < 0.01) and negatively correlated with BPD tendencies (r = -0.296, P < 0.01). Conclusion: In adolescents, PTSD in response to stressful events could lead to NSSI, and BPD tendencies promote the intensity of NSSI, while SWB diminishes its intensity. Improvement in family functioning may actively guide the development of mental health and improve SWB; such steps may constitute interventions to prevent or treat NSSI.
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Background: Non-suicidal self-injury (NSSI) has become an important public health issue of global concern, often occurring in adolescents, and depressive mood is closely related to NSSI. In addition, NSSI is considered a symptom of borderline personality disorder. It has been found that adolescents in secondary vocational schools are more vulnerable to behavior and emotional disorders than those in general high schools. This study investigated the risk factors associated with NSSI affecting secondary vocational school students and analyzed the role of borderline personality disorder tendencies in promoting the occurrence of NSSI among students with depressive moods. Methods: A total of 1,848 Chinese secondary vocational students completed a self-report questionnaire. The homemade NSSI behavior questionnaire, Patient Health Questionnaire-9 and Personality Diagnostic Questionnaire-4 were used in this survey. Binary logistic regression and PROCESS software analysis were used to explore the influencing factors associated with NSSI and to test for moderating effects. Results: Female (OR = 3.412, 95% CI 2.301-5.060), drinking history (OR = 2.007, 95% CI 1.383-2.911), history of suicidal death exposure (OR = 3.161, 95% CI 1.999-4.999), depressive mood (OR = 2.436, 95% CI 1.668-3.558) and borderline personality disorder tendencies (OR = 2.558, 95% CI = 1.764-3.711) were independent risk factors for NSSI. Borderline personality disorder tendencies (B = 0.047, p = 0.000) moderated the relationship between depressive mood and NSSI. The stronger the borderline personality tendencies, the more NSSI behavior occurred when they were depressive. Conclusions: Borderline personality disorder tendencies in secondary vocational school adolescents significantly enhance the association of depressive mood with NSSI. There is a moderating role for borderline personality disorder tendencies in depressive mood and NSSI.
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The aim of this study was to explore the breastfeeding knowledge of nursing undergraduates and the influencing factors. Human milk (HM) is one of the most effective nutritional supplies to improve early development and physical health, but the current status of breastfeeding in China is still not optimal. The breastfeeding knowledge of perinatal women influences their feeding beliefs and behavior. Nursing undergraduates, as core professionals who will care for perinatal women and provide feeding guidance in the future, can significantly affect feeding behavior of mothers and their babies, so their knowledge of breastfeeding may have a potential impact on breastfeeding in China. However, studies on breastfeeding knowledge among nursing undergraduates in China are limited. A convenience sampling method was conducted in four medical universities in China, and eligible nursing undergraduates were selected. An online survey was collected from 5 July 2022 to 5 August 2022. Categorical data were reported as number and percentage, while continuous data were reported as mean ± SD. Multivariate linear regression was used to evaluate the association between influencing factors and breastfeeding knowledge. The overall mean score of the 460 returned questionnaires was 43.991 out of 100. The pass rate of the questionnaire was only 23.04%. Nursing undergraduates had a relatively better grasp of the benefits of breastfeeding and related advice (correct rates: 67.83%). Birthplace, only child or not, the course in obstetrics and gynecological nursing, the course in pediatrics nursing, and placements in maternity or neonatology units were relevant factors for breastfeeding knowledge (p < 0.05). Nursing undergraduates showed unsatisfactory breastfeeding knowledge. It is urgent to raise the knowledge level of breastfeeding among nursing undergraduates. Medical colleges should optimally structure a curriculum of breastfeeding knowledge. Furthermore, it is also necessary to improve the public's understanding of breastfeeding and the whole society's attention to breastfeeding in China.
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Lactancia Materna , Conocimientos, Actitudes y Práctica en Salud , Lactante , Niño , Humanos , Femenino , Embarazo , Estudios Transversales , Madres , China , Encuestas y CuestionariosRESUMEN
[This retracts the article DOI: 10.1016/j.omtn.2019.11.015.].
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Accumulating evidence suggests long non-coding RNAs (lncRNAs) play crucial roles in the pathogenesis of rheumatoid arthritis (RA). Here, we aimed to define the role of HOXA transcript at the distal tip (HOTTIP) in RA pathogenesis in relation to SFRP1 methylation and Wnt signaling pathway. HOTTIP was found highly expressed, and SFRP1 was hypermethylated in RA synovial fibroblasts (RASFs). Next, gain- or loss-of-function experiments were conducted in RASFs to explore the effects of HOTTIP on the biological behaviors of RASFs. Silencing of HOTTIP or overexpression of SFRP1 inhibited RASF proliferation, invasion, and migration, while enhancing apoptosis. The relationship among HOTTIP, SFRP1, and Dnmt3b was determined using methylation-specific PCR (MSP), bisulfite sequencing PCR (BSP), RNA pull-down, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assays. The regulatory mechanisms of HOTTIP/Dnmt3b/SFRP1 were explored by altering their expression in RASFs. It was noted that HOTTIP could induce SFRP1 promoter methylation through recruitment of Dnmt3b and activate the Wnt signaling pathway. Finally, a rat RA model was established in order to evaluate the in vivo effects of HOTTIP and SFRP1, which suggested that HOTTIP silencing or SFRP1 elevation inhibited the progression of RA in vivo. Our key findings demonstrate the anti-inflammatory ability of HOTTIP silencing in RA through SFRP1 promoter demethylation. These findings support HOTTIP as a candidate anti-arthritis target.
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Hepatocellular carcinoma (HCC) is one of the most dominant causes of neoplasm-related deaths worldwide. In this study, we identify and characterize HCCL5, a novel cytoplasmic long noncoding RNA (lncRNA), as a crucial oncogene in HCC. HCCL5 promoted cell growth, G1-S transition, invasion, and metastasis while inhibiting apoptosis of HCC cells both in vitro and in vivo. Moreover, HCCL5 was upregulated in TGF-ß1-induced classical epithelial-to-mesenchymal transition (EMT) models, and this lncRNA in turn accelerated the EMT phenotype by upregulating the expression of transcription factors Snail, Slug, ZEB1, and Twist1. HCCL5 was transcriptionally driven by ZEB1 via a super-enhancer and was significantly and frequently overexpressed in human HCC tissues, correlating with worse overall survival of patients with HCC. Together, this study characterizes HCCL5 as a super-enhancer-driven lncRNA promoting HCC cell viability, migration, and EMT. Our data also suggest that HCCL5 may serve as a novel prognostic biomarker and therapeutic target in HCC. SIGNIFICANCE: These findings identify the lncRNA HCCL5 as a super-enhancer-driven oncogenic factor that promotes the malignancy of hepatocellular carcinoma.
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Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , ARN no Traducido/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Animales , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Células Hep G2 , Xenoinjertos , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , ARN no Traducido/metabolismo , Activación Transcripcional , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismo , Regulación hacia Arriba , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismoRESUMEN
Estrogen receptor (ER) plays important roles in cell growth, development and tumorigenesis. Although ER-regulated genes have been extensively investigated, little is known about roles of ER-regulated lncRNAs in breast cancer. Here, we conducted genome-wide study of ER-regulated lncRNAs by using RNA-seq, ChIP-seq and TCGA data. A total of identified 114 ER-regulated lncRNAs were identified, many of them were overexpressed in ER+ breast cancer and co-expressed with some key regulators. Silencing one of most prominent lncRNA, AP000439.3, resulted in inhibition of cell cycle progression and proliferation. Further study revealed AP000439.3 can regulate expression of CCND1 through enhancing estrogen receptor induction of CCND1. This finding revealed lncRNAs may serve as important effectors of ER in regulation of gene expression and cell phenotype in breast cancer.
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Neoplasias de la Mama/genética , Ciclina D1/genética , Receptor alfa de Estrógeno/genética , ARN Largo no Codificante/genética , Neoplasias de la Mama/patología , Carcinogénesis/genética , Ciclo Celular/genética , Proliferación Celular/genética , Estrógenos/genética , Estrógenos/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Genoma Humano , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Células MCF-7RESUMEN
PURPOSE: To investigate the biological function of HOXB5 in human bladder cancer and explore whether the HOXB5 3'-UTR SNP (1010A/G), which is located within the microRNA-7 binding site, was correlated with clinical features of bladder cancer. METHODS: Expression of HOXB5 in 35 human bladder cancer tissues and 8 cell lines were examined using real-time PCR and immunohistochemistry. Next, we explored the biological function of HOXB5 in vitro using cell proliferation, migration and colony formation assays. Using bioinformatics, a SNP (1010A/G) was found located within the microRNA-7 binding site in the 3'-UTR of HOXB5. Real-time PCR was used to test HOXB5 expression affected by different alleles. Finally, multivariate logistic regression analysis was used to determine the relationship between SNP (1010A/G) frequency and clinical features in 391 cases. RESULTS: HOXB5 was frequently over-expressed both in bladder cancer tissues and cell lines. Inhibition of HOXB5 suppressed the oncogenic function of cancer cells. Next, we demonstrated that a SNP (1010A/G), located within the microRNA-7 binding site in the 3'-UTR of HOXB5, could affect HOXB5 expression in bladder cancer mainly by differential binding activity of microRNA-7 and SNP-related mRNA stability. Finally, we also showed the frequency of 1010G genotype was higher in cancer group compared to normal controls and correlated with the risk of high grade and high stage. CONCLUSION: HOXB5 is overexpressed in bladder cancer. A miRNA-binding SNP (1010A/G) located within 3'-UTR of HOXB5 is associated with gene expression and may be a promising prognostic factor for bladder cancer.