Liraglutide prevents cellular senescence in human retinal endothelial cells (HRECs) mediated by SIRT1: an implication in diabetes retinopathy.

Diabetes mellitus (DM) is a chronic metabolic disorder affecting millions of people worldwide, characterized by dysregulated glucose homeostasis and hyperglycemia. Diabetic retinopathy (DR) is one of the serious multisystemic complications. Aging is an important risk factor for DR. Endothelial sirtuin 1 (SIRT1) plays an important role in regulating the pathophysiology of glucose metabolism, cellular senescence, and aging. Liraglutide, an analog of Glucagon-like peptide 1 (GLP-1), has been widely used in the treatment of DM. However, the effects of Liraglutide on DR are less reported. Here, we investigated whether treatment with Liraglutide has beneficial effects on high glucose (HG)-induced injury in human retinal microvascular endothelial cells (HRECs). First, we found that exposure to HG reduced the expression of glucagon-like peptide 1 receptor 1 (GLP-1R). Additionally, Liraglutide ameliorated HG-induced increase in the expression of vascular endothelial growth factor-A (VEGF-A) and interleukin 6 (IL-6). Importantly, Liraglutide ameliorated cellular senescence and increased telomerase activity in HG-challenged HRECs. Liraglutide also reduced the levels of p53 and p21. Mechanistically, Liraglutide restored the expression of SIRT1 against HG. In contrast, the knockdown of SIRT1 abolished the protective effects of Liraglutide in cellular senescence of HRECs. Our findings suggest that Liraglutide might possess a benefit on DR mediated by SIRT1.

A dataset of pomegranate growth stages for machine learning-based monitoring and analysis.

Machine learning and deep learning have grown very rapidly in recent years and are widely used in agriculture. Neat and clean datasets are a major requirement for building accurate and robust machine learning models and minimizing misclassification in real-time environments. To achieve this goal, we created a dataset of images of pomegranate growth stages. These images of pomegranate growth stages were taken from May to September from an orchard inside the Henan Institute of Science and Technology in China. The dataset contains 5857 images of pomegranates at different growth stages, which are labeled and classified into five periods: bud, flower, early-fruit, mid-growth and ripe. The dataset consists of four folders, which respectively store the images, two formats of annotation files, and the record files for the division of training, validation, and test sets. The authors have confirmed the usability of this dataset through previous research. The dataset may help researchers develop computer applications using machine learning and computer vision algorithms.

Circ_0000527 Promotes Retinoblastoma Progression through Modulating miR-98-5p/XIAP Pathway.

Purpose: Retinoblastoma (RB) is an intraocular malignancy that often occurs in childhood. Circular RNAs (circRNAs) play crucial roles in regulating the malignant phenotypes of various tumors. This study aimed to explore the role and potential mechanism of circ_0000527 in RB.Methods: The levels of circ_0000527, microRNA-98-5p (miR-98-5p) and X-linked inhibitor of apoptosis (XIAP) were determined by qRT-PCR or western blot. Cell proliferation was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and colony formation assays. Cell apoptosis, migration and invasion were evaluated by flow cytometry, transwell and scratch assays. Xenograft assay was conducted to analyze tumor growth in vivo. The binding relationship between miR-98-5p and circ_0000527 or XIAP was verified by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays.Results: Circ_0000527 and XIAP levels were increased, while miR-98-5p level was reduced in RB tissues and cells. Silencing of circ_0000527 suppressed the proliferation, migration and invasion of RB cells and promoted apoptosis. In addition, knockdown of circ_0000527 inhibited tumor growth in xenograft mice. Besides, circ_0000527 sponged miR-98-5p to regulate RB cell progression, and miR-98-5p targeted XIAP to mediate RB cell development. Moreover, circ_0000527 modulated XIAP expression via sequestering miR-98-5p.Conclusion: Circ_0000527 facilitated RB progression via regulating miR-98-5p/XIAP axis, which provided a promising therapeutic target for RB.

Regulation of ROCK1 via Notch1 during breast cancer cell migration into dense matrices.

BACKGROUND: The behaviour of tumour cells depends on factors such as genetics and the tumour microenvironment. The latter plays a crucial role in normal mammary gland development and also in breast cancer initiation and progression. Breast cancer tissues tend to be highly desmoplastic and dense matrix as a pre-existing condition poses one of the highest risk factors for cancer development. However, matrix influence on tumour cell gene expression and behaviour such as cell migration is not fully elucidated. RESULTS: We generated high-density (HD) matrices that mimicked tumour collagen content of 20 mg/cm3 that were ~14-fold stiffer than low-density (LD) matrix of 1 mg/cm3. Live-cell imaging showed breast cancer cells utilizing cytoplasmic streaming and cell body contractility for migration within HD matrix. Cell migration was blocked in the presence of both the ROCK inhibitor, Y-27632, and the MMP inhibitor, GM6001, but not by the drugs individually. This suggests roles for ROCK1 and MMP in cell migration are complicated by compensatory mechanisms. ROCK1 expression and protein activity, were significantly upregulated in HD matrix but these were blocked by treatment with a histone deacetylase (HDAC) inhibitor, MS-275. In HD matrix, the inhibition of ROCK1 by MS-275 was indirect and relied upon protein synthesis and Notch1. Inhibition of Notch1 using pooled siRNA or DAPT abrogated the inhibition of ROCK1 by MS-275. CONCLUSION: Increased matrix density elevates ROCK1 activity, which aids in cell migration via cell contractility. The upregulation of ROCK1 is epigenetically regulated in an indirect manner involving the repression of Notch1. This is demonstrated from inhibition of HDACs by MS-275, which caused an upregulation of Notch1 levels leading to blockade of ROCK1 expression.