MicroRNAs (miRNAs) regulate mammalian gene expression by targeting mRNAs and have key roles in several cellular processes, including differentiation, development, apoptosis and cancer pathomechanisms. Our previous studies have confirmed that a proliferation-inducing ligand (APRIL) gene is overexpressed in colorectal cancer (CRC) tumors and SW480 cells. To study the potential mechanisms of APRIL gene in the occurrence and development of the CRC, herein, we investigated whether APRILknockdown had the inhibitory effect on the growth of SW480 cells and had the simultaneous expression changes of miRNAs and mRNAs by microarrays. Our results suggest that siRNA-APRIL can effectively inhibit the growth of SW480 cells in vitro and in vivo and several miRNAs via specific pathways might be involved in regulating the phenotype of loss-of-function in APRIL-knockdown SW480 cells. Thus, our study highlights the possible mechanisms of miRNA-target regulating the function of APRIL gene in CRC cells, moreover, siRNA-APRIL holds great promise as a novel gene therapy approach for APRIL-positive CRC treatment.
Aims High myopia is a common visual disorder in the world. The ZNF644, GRM6, and CTNND2 genes are expressed in the retina. This study aims to investigate the associations of these genes with high myopia in Han Chinese population. Methods The case-control association included high myopia cases (n = 430) and controls (n = 430) recruited from a populationbased study, 'Jiangsu Eye Study'. Fourteen single-nucleotide polymorphisms (SNPs) in three genes were genotyped by the TaqMan method using the real-time PCR system. Results Three SNPs GRM6-rs11746675, GRM6-rs2067011, and GRM6-rs2645339 were associated with high myopia (odds ratio (OR) = 0.74, P = 0.003; OR = 0.78, P = 0.018; and OR = 0.78, P = 0.023; respectively). The significances of rs2067011 and rs2645339 disappeared after multiple testing corrections. Rs11746675 remained significant after correction for multiple testing. The genetic model analysis found that GRM6-rs11746675 and GRM6-rs2067011 were suggestively associated with high myopia in the recessive model (OR = 0.54, P = 0.004; OR = 0.52, P = 0.003; respectively). Haplotype GAT for GRM6 markers rs2067011-rs2645339-rs762724 showed significance (P = 0.0239), but such association did not remain significant after multiple testing corrections. Conclusions Our data suggested that genetic variants in GRM6 are associated with high myopia. The mechanism of GRM6 in the development of high myopia need to be further investigated.
Background: Microfracture at the rotator cuff insertion is an established surgical marrow-stimulation technique for enhancing rotator cuff healing. However, the effect of lateralized or medialized microfracture on the insertion is unknown. Purpose: To compare the biomechanical and histologic effects of microfracture at 3 different regions for rotator cuff repair in a rat model. Study Design: Controlled laboratory study. Methods: A total of 72 Sprague-Dawley rats with bilateral supraspinatus tendon insertion detachment were allocated into 4 groups with 4 different interventions: no microfracture at the humeral head as a control group (Con), traditional microfracture at the footprint area (MFA), and medialized microfracture to the footprint area (MMFA) on the articular surface of the humerus or lateralized microfracture to the footprint area at the greater tuberosity (LMFA). All underwent immediate repair. Tendon-to-bone healing was assessed by biomechanical and histologic tests 4 and 8 weeks postoperation. Results: At 4 weeks, the LMFA group showed a significantly superior failure load compared with the other groups (all P < .05). The LMFA and MFA groups showed significantly superior stiffness compared with the Con and MMFA groups (all P < .01). At 8 weeks, superior failure load and stiffness were observed in the LMFA group compared with the control group (all P < .05). Histologic examination revealed that the LMFA group had superior collagen composition and tendon-to-bone maturation at the interface at 4 and 8 weeks compared with the Con group (all P < .05). Conclusion: Lateralized microfracture at the greater tuberosity improved the histologic quality of repair tissue and biomechanical strength at the tendon-to-bone insertion after rotator cuff repair in a rat model. Clinical Relevance: Microfracture lateral to the footprint area might be a better way to enhance rotator cuff healing clinically.
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