Additional file 1 of BML-111 inhibit H2O2-induced pyroptosis and osteogenic dysfunction of human periodontal ligament fibroblasts by activating the Nrf2/HO-1 pathway

Supplementary Material

MOESM1 of Repressed SIRT1/PGC-1Îą pathway and mitochondrial disintegration in iPSC-derived RPE disease model of age-related macular degeneration

Additional file 1. Additional figures and tables

DataSheet_1_A novel genomic instability-derived lncRNA signature to predict prognosis and immune characteristics of pancreatic ductal adenocarcinoma.docx

BackgroundPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignant tumor of the digestive system. Its grim prognosis is mainly attributed to the lack of means for early diagnosis and poor response to treatments. Genomic instability is shown to be an important cancer feature and prognostic factor, and its pattern and extent may be associated with poor treatment outcomes in PDAC. Recently, it has been reported that long non-coding RNAs (lncRNAs) play a key role in maintaining genomic instability. However, the identification and clinical significance of genomic instability-related lncRNAs in PDAC have not been fully elucidated.MethodsGenomic instability-derived lncRNA signature (GILncSig) was constructed based on the results of multiple regression analysis combined with genomic instability-associated lncRNAs and its predictive power was verified by the Kaplan-Meier method. And real-time quantitative polymerase chain reaction (qRT-PCR) was used for simple validation in human cancers and their adjacent non-cancerous tissues. In addition, the correlation between GILncSig and tumor microenvironment (TME) and epithelial-mesenchymal transition (EMT) was investigated by Pearson correlation analysis.ResultsThe computational framework identified 206 lncRNAs associated with genomic instability in PDAC and was subsequently used to construct a genome instability-derived five lncRNA-based gene signature. Afterwards, we successfully validated its prognostic capacity in The Cancer Genome Atlas (TCGA) cohort. In addition, via careful examination of the transcriptome expression profile of PDAC patients, we discovered that GILncSig is associated with EMT and an adaptive immunity deficient immune profile within TME.ConclusionsOur study established a genomic instability-associated lncRNAs-derived model (GILncSig) for prognosis prediction in patients with PDAC, and revealed the potential functional regulatory role of GILncSig.</p

Osteoprotegerin Inhibits Aortic Valve Calcification and Preserves Valve Function in Hypercholesterolemic Mice

<div><p>Background</p><p>There are no rigorously confirmed effective medical therapies for calcific aortic stenosis. Hypercholesterolemic <i>Ldlr</i>^−/−<i>Apob</i>^100/100 mice develop calcific aortic stenosis and valvular cardiomyopathy in old age. Osteoprotegerin (OPG) modulates calcification in bone and blood vessels, but its effect on valve calcification and valve function is not known.</p><p>Objectives</p><p>To determine the impact of pharmacologic treatment with OPG upon aortic valve calcification and valve function in aortic stenosis-prone hypercholesterolemic <i>Ldlr</i>^−/−<i>Apob</i>^100/100 mice.</p><p>Methods</p><p>Young <i>Ldlr</i>^−/−<i>Apob</i>^100/100 mice (age 2 months) were fed a Western diet and received exogenous OPG or vehicle (N = 12 each) 3 times per week, until age 8 months. After echocardiographic evaluation of valve function, the aortic valve was evaluated histologically. Older <i>Ldlr</i>^−/−<i>Apob</i>^100/100 mice were fed a Western diet beginning at age 2 months. OPG or vehicle (N = 12 each) was administered from 6 to 12 months of age, followed by echocardiographic evaluation of valve function, followed by histologic evaluation.</p><p>Results</p><p>In Young <i>Ldlr</i>^−/−<i>Apob</i>^100/100 mice, OPG significantly attenuated osteogenic transformation in the aortic valve, but did not affect lipid accumulation. In Older <i>Ldlr</i>^−/−<i>Apob</i>^100/100 mice, OPG attenuated accumulation of the osteoblast-specific matrix protein osteocalcin by ∼80%, and attenuated aortic valve calcification by ∼ 70%. OPG also attenuated impairment of aortic valve function.</p><p>Conclusions</p><p>OPG attenuates pro-calcific processes in the aortic valve, and protects against impairment of aortic valve function in hypercholesterolemic aortic stenosis-prone <i>Ldlr</i>^−/−<i>Apob</i>^100/100 mice.</p></div

MOESM1 of DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways

Additional file 1: Figure S1. The effect of DDIT4 downregulation on GC cell migration and invasion

MOESM2 of DDIT4 promotes gastric cancer proliferation and tumorigenesis through the p53 and MAPK pathways

Additional file 2: Table S1. The effect of DDIT4-knockdown on phosphorylation of signal protein

Immunostaining for monocyte chemo-attractant protein-1 (MCP-1) in Older LA mice.

<p>OPG decreased levels of MCP-1 in the aortic valve. N = 11 (Veh) and N = 6 (OPG). *p<0.05 for Veh vs. OPG.</p

Calcification in the aortic valve.

<p>Alizarin Red staining in a valve from an Older vehicle-treated mouse (<b>A,C</b>) demonstrates bright red staining, indicating valve calcification (arrows). Valve cusps are thickened in an Older OPG-treated mouse, but are minimally calcified (<b>B,D</b>). Dashed borders contain valve cusps, with care taken to exclude the aortic annulus (aa). Group data for valve calcification in Young mice (E) and Older mice (F). *p<0.05 Veh vs. OPG, N = 12.</p

Morphometric and metabolic parameters.

<p><b>Veh-LA:</b> vehicle-treated Ldlr^−/−Apob^100/100 mice; <b>OPG-LA</b>: osteoprotegerin-treated Ldlr^−/−Apob^100/100 mice.</p>*<p>p<0.05 vs. Veh-LA;</p>†<p>p<0.05 vs. Young mice.</p

Additional file 7: of miR-148b-3p inhibits gastric cancer metastasis by inhibiting the Dock6/Rac1/Cdc42 axis

Table S4. microRNAs that could target Dock6 as predicted by Target scan, Microcosm, miRDB and PicTar databases. (DOCX 22 kb