cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.12601360.v1
title: MiR-1247-3p protects rat cardiomyocytes against hypoxia/reoxygenation-induced injury via targeting BCL2L11 and caspase-2

description: Acute myocardial infarction (AMI) represents a severe coronary heart disease with relatively high rate of mortality and usually can lead to the damage of the myocardial tissues. Reperfusion of the ischemic myocardial tissues can minimize AMI-induced damage. As far as we know, the molecular mechanisms underlying ischemia/reperfusion (I/R)-induced injury remains elusive. This study was undertaken to explore the role of miR-1247-3p in regulating myocardial I/R injury. The hypoxia/reoxygenation (H/R)-treated H9c2 cells showed a decreased cell viability and mitochondrial membrane potential with an increase in the apoptosis; furthermore, miR-1247-3p was down-regulated in these cells. MiR-1247-3p overexpression attenuated H/R-induced H9c2 cell injury; while miR-1247-3p knockdown in H9c2 cells exhibited similar effects being observed in H/R-treated cells. The bioinformatics prediction revealed Bcl-2-like protein 11 (BCL2L11) and caspase-2 were two potential targets for miR-1247-3p, and functional assays confirmed that miR-1247-3p targeted both BCL2L11 and caspase-2 3′ untranslated regions, which lead to the repressed expression of these genes. Silencing of BCL2L11 and caspase-2 both, respectively, counteracted the H9c2 cell injury caused by H/R treatment. Moreover, BCL2L11 and caspase-2 overexpression, respectively, impaired the protective effects of miR-1247-3p overexpression on H/R-treated H9c2 cells. The data in the present investigation revealed that miR-1247-3p restoration exhibited protective effects on H/R-induced cardiomyocyte injury through targeting BCL2L11 and caspase-2, implying that miR-1247-3p along with caspase-2/BCL2L11 signaling may provide novel sight for a better understating of I/R-induced myocardial damage. The role of miR-1247-3p might be further confirmed in animal models and clinical studies.
DOI: 10.6084/m9.figshare.9980765
title: Discovery of potent apoptosis signal-regulating kinase 1 inhibitors via integrated computational strategy and biological evaluation

description: Apoptosis signal-regulating Kinase 1 (ASK1) has been confirmed as a potential therapeutic target for the treatment of non-alcoholic steatohepatitis (NASH) disorder and the discovery of ASK1 inhibitors has attracted increasing attention. In this work, a series of in silico methods including pharmacophore screening, docking binding site analysis, protein-ligand interaction fingerprint (PLIF) similarity investigation and molecular docking were applied to find the potential hits from commercial compound databases. Five compounds with potential inhibitory activity were purchased and submitted to biological activity validation. Thus, one hit compound was discovered with micromolar IC<sub>50</sub> value (10.59 μM) against ASK1. Results demonstrated that the integration of computation methods and biological test was quite reliable for the discovery of potent ASK1 inhibitors and the strategy could be extended to other similar targets of interest. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.9980765.v2
title: Discovery of potent apoptosis signal-regulating kinase 1 inhibitors via integrated computational strategy and biological evaluation

description: Apoptosis signal-regulating Kinase 1 (ASK1) has been confirmed as a potential therapeutic target for the treatment of non-alcoholic steatohepatitis (NASH) disorder and the discovery of ASK1 inhibitors has attracted increasing attention. In this work, a series of in silico methods including pharmacophore screening, docking binding site analysis, protein-ligand interaction fingerprint (PLIF) similarity investigation and molecular docking were applied to find the potential hits from commercial compound databases. Five compounds with potential inhibitory activity were purchased and submitted to biological activity validation. Thus, one hit compound was discovered with micromolar IC<sub>50</sub> value (10.59 μM) against ASK1. Results demonstrated that the integration of computation methods and biological test was quite reliable for the discovery of potent ASK1 inhibitors and the strategy could be extended to other similar targets of interest. Communicated by Ramaswamy H. Sarma
DOI: 10.6084/m9.figshare.19941376
title: Association between the Severity of Coronary Artery Disease and Lung Cancer: A Pilot Cross-Sectional Study

description: Abstract Background The direct relationship between coronary artery disease (CAD) and lung cancer is not well known. Objective To investigate the association between the anatomical severity of CAD and lung cancer. Methods Three-hundred study patients, including 75 recently diagnosed lung cancer patients and 225 matched non-cancer patients, underwent coronary angiography during hospitalization without previous percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The SYNTAX score (SXscore) was used to assess the severity of CAD. A high SXscore (SXhigh) grade was defined as SXscore &gt; 15 (the highest quartile of the SXscore). The Cochran-Armitage test for trend was used to assess the distribution of patients’ SXscores. Logistic regression analysis was used to assess the association between the severity of CAD and lung cancer. P-values were set when significance level was 5%. Results The distribution trend of patients’ SXscore by quartiles was different between lung cancer patients and control patients (from the lowest to the highest quartile: 20.0%, 20.0%, 24.0%, 36.0% vs. 26.7%, 26.2%, 25.8%, 21.3%, p=0.022). The SX high rate was higher in lung cancer patients than in control patients (36.0% vs. 21.3%, p=0.011).The highest quartile of the SXscore showed higher risk of lung cancer in comparison to the lowest quartile (OR: 2,250, 95%CI: 1,077 to 4,699 ; P-trend= 0.016). After adjustment, patients in the highest quartile of the SXscore had higher risk of lung cancer (OR: 2,149, 95%CI: 1,008 to 4,584; P-trend= 0.028). Patients with high SXscore (&gt; 15) had 1,985 times more chances of having lung cancer (95%CI: 1,105–3,563, P= 0.022). Conclusions The anatomical severity of CAD is associated with the risk of lung cancer, which indicates that a thorough lung cancer screening may be significant among severe CAD patients.
DOI: 10.6084/m9.figshare.19941376.v1
title: Association between the Severity of Coronary Artery Disease and Lung Cancer: A Pilot Cross-Sectional Study

description: Abstract Background The direct relationship between coronary artery disease (CAD) and lung cancer is not well known. Objective To investigate the association between the anatomical severity of CAD and lung cancer. Methods Three-hundred study patients, including 75 recently diagnosed lung cancer patients and 225 matched non-cancer patients, underwent coronary angiography during hospitalization without previous percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). The SYNTAX score (SXscore) was used to assess the severity of CAD. A high SXscore (SXhigh) grade was defined as SXscore &gt; 15 (the highest quartile of the SXscore). The Cochran-Armitage test for trend was used to assess the distribution of patients’ SXscores. Logistic regression analysis was used to assess the association between the severity of CAD and lung cancer. P-values were set when significance level was 5%. Results The distribution trend of patients’ SXscore by quartiles was different between lung cancer patients and control patients (from the lowest to the highest quartile: 20.0%, 20.0%, 24.0%, 36.0% vs. 26.7%, 26.2%, 25.8%, 21.3%, p=0.022). The SX high rate was higher in lung cancer patients than in control patients (36.0% vs. 21.3%, p=0.011).The highest quartile of the SXscore showed higher risk of lung cancer in comparison to the lowest quartile (OR: 2,250, 95%CI: 1,077 to 4,699 ; P-trend= 0.016). After adjustment, patients in the highest quartile of the SXscore had higher risk of lung cancer (OR: 2,149, 95%CI: 1,008 to 4,584; P-trend= 0.028). Patients with high SXscore (&gt; 15) had 1,985 times more chances of having lung cancer (95%CI: 1,105–3,563, P= 0.022). Conclusions The anatomical severity of CAD is associated with the risk of lung cancer, which indicates that a thorough lung cancer screening may be significant among severe CAD patients.
DOI: 10.6084/m9.figshare.7357895
title: Luteolin inhibits Musashi1 binding to RNA and disrupts cancer phenotypes in glioblastoma cells

description: RNA binding proteins have emerged as critical oncogenic factors and potential targets in cancer therapy. In this study, we evaluated Musashi1 (Msi1) targeting as a strategy to treat glioblastoma (GBM); the most aggressive brain tumor type. Msi1 expression levels are often high in GBMs and other tumor types and correlate with poor clinical outcome. Moreover, Msi1 has been implicated in chemo- and radio-resistance. Msi1 modulates a range of cancer relevant processes and pathways and regulates the expression of stem cell markers and oncogenic factors via mRNA translation/stability. To identify Msi1 inhibitors capable of blocking its RNA binding function, we performed a ~25,000 compound fluorescence polarization screen. NMR and LSPR were used to confirm direct interaction between Msi1 and luteolin, the leading compound. Luteolin displayed strong interaction with Msi1 RNA binding domain 1 (RBD1). As a likely consequence of this interaction, we observed via western and luciferase assays that luteolin treatment diminished Msi1 positive impact on the expression of pro-oncogenic target genes. We tested the effect of luteolin treatment on GBM cells and showed that it reduced proliferation, cell viability, colony formation, migration and invasion of U251 and U343 GBM cells. Luteolin also decreased the proliferation of patient-derived glioma initiating cells (GICs) and tumor-organoids but did not affect normal astrocytes. Finally, we demonstrated the value of combined treatments with luteolin and olaparib (PARP inhibitor) or ionizing radiation (IR). Our results show that luteolin functions as an inhibitor of Msi1 and demonstrates its potential use in GBM therapy.
DOI: 10.6084/m9.figshare.20465310.v2
title: <i>iProMix</i>: A mixture model for studying the function of ACE2 based on bulk proteogenomic data

description: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused over six million deaths in the ongoing COVID-19 pandemic. SARS-CoV-2 uses ACE2 protein to enter human cells, raising a pressing need to characterize proteins/pathways interacted with ACE2. Large-scale proteomic profiling technology is not mature at single-cell resolution to examine the protein activities in disease-relevant cell types. We propose <i>iProMix</i>, a novel statistical framework to identify epithelial-cell specific associations between ACE2 and other proteins/pathways with bulk proteomic data. <i>iProMix</i> decomposes the data and models cell-type-specific conditional joint distribution of proteins through a mixture model. It improves cell-type composition estimation from prior input, and utilizes a non-parametric inference framework to account for uncertainty of cell-type proportion estimates in hypothesis test. Simulations demonstrate <i>iProMix</i> has well-controlled false discovery rates and favorable powers in non-asymptotic settings. We apply <i>iProMix</i> to the proteomic data of 110 (tumor-adjacent) normal lung tissue samples from the Clinical Proteomic Tumor Analysis Consortium lung adenocarcinoma study, and identify interferon α/γ response pathways as the most significant pathways associated with ACE2 protein abundances in epithelial cells. Strikingly, the association direction is sex-specific. This result casts light on the sex difference of COVID-19 incidences and outcomes, and motivates sex-specific evaluation for interferon therapies.
DOI: 10.6084/m9.figshare.12601357.v1
title: MiR-199a-3p inhibits the proliferation, migration, and invasion of endothelial cells and retinal pericytes of diabetic retinopathy rats through regulating FGF7 via EGFR/PI3K/AKT pathway

description: MiR-199a-3p is low expressed in diabetic retinopathy (DR). In the current study, we investigated the effects of miR-199a-3p on DR and the potential mechanisms. A DR rat model was established, and endothelial cells (ECs) and retinal pericytes (RPs) were extracted from the DR model rats to detect miR-199a-3p expression. Bioinformatics analysis predicted that fibroblast growth factor 7 (FGF7) was a target gene for miR-199a-3p, which was confirmed by dual-luciferase assay. Cell proliferation, migration, and invasion were detected by cell counting kit-8 (CCK-8), colony formation assay, wound-healing, and Transwell assay. Quantitative real-time polymerase chain reaction (q-PCR) and Western blot were performed to detect the expressions of mRNAs and proteins. MiR-199a-3p was low expressed and FGF7 was high-expressed in ECs and RPs. Overexpressed miR-199a-3p suppressed the proliferation, migration, and invasion, and FGF7 expression of ECs and RPs. However, overexpression of FGF7 effectively eliminated the suppressive effects of miR-199a-3p overexpression malignant behaviors of the cells. Meanwhile, up-regulation of FGF7 noticeably reversed the phosphorylation of phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) and the expression of epidermal growth factor receptor (EGFR) reduced by miR-199a-3p. Our findings revealed that in the DR rat model, miR-199a-3p inhibited cell proliferation, migration, and invasion of EC and RP through targeting FGF7 and inhibiting the activation of the EGFR/PI3K/AKT pathway. This study may provide a new direction for the search for the treatment of DR.
DOI: 10.6084/m9.figshare.16780895
title: Additional file 7 of Multi-omics colocalization with genome-wide association studies reveals a context-specific genetic mechanism at a childhood onset asthma risk locus

description: Additional file 7:. FastQTL eQTL mapping results for RV-treated AECs (FDR&lt; 0.05).
DOI: 10.6084/m9.figshare.12601360
title: MiR-1247-3p protects rat cardiomyocytes against hypoxia/reoxygenation-induced injury via targeting BCL2L11 and caspase-2

description: Acute myocardial infarction (AMI) represents a severe coronary heart disease with relatively high rate of mortality and usually can lead to the damage of the myocardial tissues. Reperfusion of the ischemic myocardial tissues can minimize AMI-induced damage. As far as we know, the molecular mechanisms underlying ischemia/reperfusion (I/R)-induced injury remains elusive. This study was undertaken to explore the role of miR-1247-3p in regulating myocardial I/R injury. The hypoxia/reoxygenation (H/R)-treated H9c2 cells showed a decreased cell viability and mitochondrial membrane potential with an increase in the apoptosis; furthermore, miR-1247-3p was down-regulated in these cells. MiR-1247-3p overexpression attenuated H/R-induced H9c2 cell injury; while miR-1247-3p knockdown in H9c2 cells exhibited similar effects being observed in H/R-treated cells. The bioinformatics prediction revealed Bcl-2-like protein 11 (BCL2L11) and caspase-2 were two potential targets for miR-1247-3p, and functional assays confirmed that miR-1247-3p targeted both BCL2L11 and caspase-2 3′ untranslated regions, which lead to the repressed expression of these genes. Silencing of BCL2L11 and caspase-2 both, respectively, counteracted the H9c2 cell injury caused by H/R treatment. Moreover, BCL2L11 and caspase-2 overexpression, respectively, impaired the protective effects of miR-1247-3p overexpression on H/R-treated H9c2 cells. The data in the present investigation revealed that miR-1247-3p restoration exhibited protective effects on H/R-induced cardiomyocyte injury through targeting BCL2L11 and caspase-2, implying that miR-1247-3p along with caspase-2/BCL2L11 signaling may provide novel sight for a better understating of I/R-induced myocardial damage. The role of miR-1247-3p might be further confirmed in animal models and clinical studies.
DOI: 10.6084/m9.figshare.12601150
title: Biodistribution of etoposide via intratumoral chemotherapy with etoposide-loaded implants

description: Etoposide (VP16) is the traditional antitumor agent which has been widely used in a variety of cancers. However, intravenous administration of VP16 was limited in clinical application because of its low aqueous solubility, poor bioavailability and dose-limiting adverse effects. Local chemotherapy with VP16-loaded drug delivery systems could provide a continuous release of drug at the target site, while minimizing the systemic toxicity. In this study, we prepared the poly-l-lactic acid (PLLA) based VP16-loaded implants (VP16 implants) by the direct compression method. The VP16 implants were characterized with regards to drug content, micromorphology, drug release profiles, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) analyses. Furthermore, the biodistribution of VP16 via intratumoral chemotherapy with VP16 implants was investigated using the murine Lewis lung carcinoma model. Our results showed that VP16 dispersed homogenously in the polymeric matrix. Both <i>in vitro</i> and in <i>vivo</i> drug release profiles of the implants were characterized by high initial burst release followed by sustained release of VP16. The VP16 implants showed good compatibility between VP16 and the excipients. Intratumoral chemotherapy with VP16 implants resulted in significantly higher concentration and longer duration of VP16 in tumor tissues compared with single intraperitoneal injection of VP16 solution. Moreover, we found the low level of VP16 in plasma and normal organ tissues. These results suggested that intratumoral chemotherapy with VP16 implants enabled high drug concentration at the target site and has the potential to be used as a novel method to treat cancer.
DOI: 10.6084/m9.figshare.7358573.v1
title: Supplemental Data file-Raw data from Comment on van Casteren <i>et al</i>. (2018): softer metallic spheres do abrade harder enamel

description: Raw data summarized in this paper
DOI: 10.6084/m9.figshare.13125277
title: Pygmaeomycetaceae, a new root-associated family in Mucoromycotina from the pygmy pine plains

description: A new genus, <i>Pygmaeomyces</i>, and two new species are described based on phylogenetic analyses and phenotypic and ecological characters. The species delimitation was based on concordance of gene genealogies. The <i>Pygmaeomyces</i> cultures were isolated from the roots of mountain laurel (<i>Kalmia latifolia</i>) and pitch pine (<i>Pinus rigida</i>) from the acidic and oligotrophic New Jersey pygmy pine plains; however, they likely have a broader distribution because their internal transcribed spacer (ITS) sequences have high similarity to a number of environmental sequences from multiple independent studies. Based on the phylogeny and phenotypic characters, a new family, Pygmaeomycetaceae, is proposed to accommodate this new lineage in Mucoromycotina. Pygmaeomycetaceae corresponds to Clade GS23, which was identified based on a sequence-only soil fungal survey and was believed to be a distinct new class. Compared with the culture-based methods, we observed that sequence-only analyses tend to overestimate the taxonomic level. Results from this work will facilitate ecological and evolutionary studies on root-associated fungi.
DOI: 10.6084/m9.figshare.14699494
title: Energy restriction causes metaphase delay and chromosome mis-segregation in cancer cells

description: ATP metabolism during mitosis needs to be coordinated with numerous energy-demanding activities, especially in cancer cells whose metabolic pathways are reprogramed to sustain rapid proliferation in a nutrient-deficient environment. Although strategies targeting the energy metabolic pathways have shown therapeutic efficacy in preclinical cancer models, how normal cells and cancer cells differentially respond to energy shortage is unclear. In this study, using time-lapse microscopy, we found that cancer cells displayed unique mitotic phenotypes in a dose-dependent manner upon decreasing ATP (i.e. energy) supply. When reduction in ATP concentration was moderate, chromosome movements in mitosis were barely affected, while the metaphase–anaphase transition was significantly prolonged due to reduced tension between the sister-kinetochores, which delayed the satisfaction of the spindle assembly checkpoint. Further reduction in ATP concentration led to a decreased level of Aurora-B at the centromere, resulting in increased chromosome mis-segregation after metaphase delay. In contrast to cancer cells, ATP restriction in non-transformed cells induced cell cycle arrest in interphase, rather than causing mitotic defects. In addition, data mining of cancer patient database showed a correlation between signatures of energy production and chromosomal instability possibly resulted from mitotic defects. Together, these results reveal that energy restriction induces differential responses in normal and cancer cells, with chromosome mis-segregation only observed in cancer cells. This points to targeting energy metabolism as a potentially cancer-selective therapeutic strategy.
DOI: 10.6084/m9.figshare.12601150.v1
title: Biodistribution of etoposide via intratumoral chemotherapy with etoposide-loaded implants

description: Etoposide (VP16) is the traditional antitumor agent which has been widely used in a variety of cancers. However, intravenous administration of VP16 was limited in clinical application because of its low aqueous solubility, poor bioavailability and dose-limiting adverse effects. Local chemotherapy with VP16-loaded drug delivery systems could provide a continuous release of drug at the target site, while minimizing the systemic toxicity. In this study, we prepared the poly-l-lactic acid (PLLA) based VP16-loaded implants (VP16 implants) by the direct compression method. The VP16 implants were characterized with regards to drug content, micromorphology, drug release profiles, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) analyses. Furthermore, the biodistribution of VP16 via intratumoral chemotherapy with VP16 implants was investigated using the murine Lewis lung carcinoma model. Our results showed that VP16 dispersed homogenously in the polymeric matrix. Both <i>in vitro</i> and in <i>vivo</i> drug release profiles of the implants were characterized by high initial burst release followed by sustained release of VP16. The VP16 implants showed good compatibility between VP16 and the excipients. Intratumoral chemotherapy with VP16 implants resulted in significantly higher concentration and longer duration of VP16 in tumor tissues compared with single intraperitoneal injection of VP16 solution. Moreover, we found the low level of VP16 in plasma and normal organ tissues. These results suggested that intratumoral chemotherapy with VP16 implants enabled high drug concentration at the target site and has the potential to be used as a novel method to treat cancer.