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he impact of TN, there remains an unmet medical need for additional treatment options.
Arecoline is an alkaloid natural product found in the areca nut that can induce oral submucous fibrosis and subsequent development of cancer. However, numerous studies have shown that arecoline may inhibit fibroblast proliferation and prevent collagen synthesis.
High doses of arecoline (> 32 μg/ml) could inhibit human oral fibroblast proliferation, while low doses of arecoline (< 16 μg/ml) could promote the proliferation of human oral fibroblasts. Wnt5a was found to be both sufficient and necessary for the promotion of fibroblast proliferation. Egr-1 could mediate the expression of Wnt5a in fibroblasts, while NF-κB, FOXO1, Smad2, and Smad3 did not. Treatment with siRNAs specific to Egr-1, Egr inhibitors, or Wnt5a antibody treatment could all inhibit arecoline-induced Wnt5a upregulation and fibroblast proliferation.
Egr-1 mediates the effect of low dose arecoline treatment on human oral mucosa fibroblast proliferation by transactivating the expression of Wnt5a. Therefore, Egr inhibitors and Wnt5a antibodies are potential therapies for treatment of oral submucosal fibrosis and oral cancer.
Egr-1 mediates the effect of low dose arecoline treatment on human oral mucosa fibroblast proliferation by transactivating the expression of Wnt5a. Therefore, Egr inhibitors and Wnt5a antibodies are potential therapies for treatment of oral submucosal fibrosis and oral cancer.
Drought-tolerance ensures a crop to maintain life activities and protect cell from damages under dehydration. It refers to diverse mechanisms temporally activated when the crop adapts to drought. However, knowledge about the temporal dynamics of rice transcriptome under drought is limited.
Here, we investigated temporal transcriptomic dynamics in 12 rice genotypes, which varied in drought tolerance (DT), under a naturally occurred drought in fields. The tolerant genotypes possess less differentially expressed genes (DEGs) while they have higher proportions of upregulated DEGs. Tolerant and susceptible genotypes have great differences in temporally activated biological processes (BPs) during the drought period and at the recovery stage based on their DEGs. The DT-featured BPs, which are activated specially (e.g. raffinose, fucose, and trehalose metabolic processes, etc.) or earlier in the tolerant genotypes (e.g. find more protein and histone deacetylation, protein peptidyl-prolyl isomerization, transcriptional attenuation, ferric iron transport, etc.) shall contribute to DT. Meanwhile, the tolerant genotypes and the susceptible genotypes also present great differences in photosynthesis and cross-talks among phytohormones under drought. A certain transcriptomic tradeoff between DT and productivity is observed. Tolerant genotypes have a better balance between DT and productivity under drought by activating drought-responsive genes appropriately. Twenty hub genes in the gene coexpression network, which are correlated with DT but without potential penalties in productivity, are recommended as good candidates for DT.
Findings of this study provide us informative cues about rice temporal transcriptomic dynamics under drought and strengthen our system-level understandings in rice DT.
Findings of this study provide us informative cues about rice temporal transcriptomic dynamics under drought and strengthen our system-level understandings in rice DT.
Neuropathic pain belongs to chronic pain and is caused by the primary dysfunction of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) have been reported to regulate neuronal functions and play significant roles in neuropathic pain. DLEU1 has been indicated to have close relationship with neuropathic pain. Therefore, our study focused on the significant role of DLEU1 in neuropathic pain rat models.
We first constructed a chronic constrictive injury (CCI) rat model. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were employed to evaluate hypersensitivity in neuropathic pain. RT-qPCR was performed to analyze the expression of target genes. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect the concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and IL-1β. The underlying mechanisms of DLEU1 were investigated using western blot and luciferase reporter assays.
Our findings showed that DLEU1 was upregulated in CCI rats. DLEU1 knockdown reduced the concentrations of IL-6, IL-1β and TNF-α in CCI rats, suggesting that neuroinflammation was inhibited by DLEU1 knockdown. Besides, knockdown of DLEU1 inhibited neuropathic pain behaviors. Moreover, it was confirmed that DLEU1 bound with miR-133a-3p and negatively regulated its expression. SRPK1 was the downstream target of miR-133a-3p. DLEU1 competitively bound with miR-133a-3p to upregulate SRPK1. Finally, rescue assays revealed that SRPK1 overexpression rescued the suppressive effects of silenced DLEU1 on hypersensitivity in neuropathic pain and inflammation of spinal cord in CCI rats.
DLEU1 regulated inflammation of the spinal cord and mediated hypersensitivity in neuropathic pain in CCI rats by binding with miR-133a-3p to upregulate SRPK1 expression.
DLEU1 regulated inflammation of the spinal cord and mediated hypersensitivity in neuropathic pain in CCI rats by binding with miR-133a-3p to upregulate SRPK1 expression.
Deep neural networks (DNN) are a particular case of artificial neural networks (ANN) composed by multiple hidden layers, and have recently gained attention in genome-enabled prediction of complex traits. Yet, few studies in genome-enabled prediction have assessed the performance of DNN compared to traditional regression models. Strikingly, no clear superiority of DNN has been reported so far, and results seem highly dependent on the species and traits of application. Nevertheless, the relatively small datasets used in previous studies, most with fewer than 5000 observations may have precluded the full potential of DNN. Therefore, the objective of this study was to investigate the impact of the dataset sample size on the performance of DNN compared to Bayesian regression models for genome-enable prediction of body weight in broilers by sub-sampling 63,526 observations of the training set.
Predictive performance of DNN improved as sample size increased, reaching a plateau at about 0.32 of prediction correlation when 60% of the entire training set size was used (i.
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