cometadata/datacite-titles-descriptions-related-identifiers huggingface dataset:
DOI: 10.6084/m9.figshare.21952762.v1
title: CircRNA hsa_circ_0070659 predicts poor prognosis and promotes non-small cell lung cancer (NSCLC) progression via microRNA-377 (miR-377) / Ras-Associated Binding Protein 3C (RAB3C) pathway

description: A large number of circular RNAs (circRNAs) are dysregulated in lung cancer and affect the progression and prognosis of lung disease. Herein, this study selected specific circular RNA (circ_0070659) by bioinformatics analysis and aimed to investigate the role of circ_0070659 in non-small cell lung cancer (NSCLC). The differentially expressed circRNA (hsa_circ_0070659) in NSCLC was screened from public databases (GEO), and real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to identify the circ_0070659 levels in cancer tissues and cells. NSCLC cell proliferation, migration, and invasion abilities after circ_0070659 silencing was detected by colony formation assay, Cell Counting Kit-8 (CCK-8) assay and Transwell assay. Targeted binding between microRNA-377 (miR-377) and circ_0070659 or Ras-Associated Binding Protein 3C (RAB3C) was verified by western blot, dual-luciferase reporter assay, and RNA pull-down assay. Our experimental results showed that circ_0070659 levels were largely increased in tumor tissues and cells. Biologically, knockdown of circ_0070659 obviously inhibited proliferation, migration, and invasion of NSCLC cells. Mechanistically, circ_0070659 promoted RAB3C-mediated proliferation and invasion through sponging miR-377. Furthermore, miR-377 inhibitor reversed the inhibitory ability of circ_0070659 silencing on malignant biological behavior of NSCLC cells. Our study revealed a novel signaling pathway that circ_0070659/miR-377/RAB3C axis regulates tumor progression, and it may become a new therapeutic target for NSCLC.
DOI: 10.6084/m9.figshare.21952742
title: Aging deteriorated liver Ischemia and reperfusion injury by suppressing Tribble’s proteins 1 mediated macrophage polarization

description: Aggravated liver injury has been reported in aged ischemia/reperfusion-stressed livers; however, the mechanism of aged macrophage inflammatory regulation is not well understood. Here, we found that the adaptor protein TRIB1 plays a critical role in the differentiation of macrophages and the inflammatory response in the liver after ischemia/reperfusion injury. In the present study, we determined that aging promoted macrophage-mediated liver injury and that inflammation was mainly responsible for lower M2 polarization in liver transplantation-exposed humans post I/R. Young and aged mice were subjected to hepatic I/R modeling and showed that aging aggravated liver injury and suppressed macrophage TRIB1 protein expression and anti-inflammatory function in I/R‐stressed livers. Restoration of TRIB1 is mediated by lentiviral infection-induced macrophage anti-inflammatory M2 polarization and alleviated hepatic I/R injury. Moreover, TRIB1 overexpression in macrophages facilitates M2 polarization and anti-inflammation by activating MEK1-ERK1/2 signaling under IL-4 stimulation. Taken together, our results demonstrated that aging promoted hepatic I/R injury by suppressing TRIB1-mediated MEK1-induced macrophage M2 polarization and anti-inflammatory function.
DOI: 10.6084/m9.figshare.21952742.v1
title: Aging deteriorated liver Ischemia and reperfusion injury by suppressing Tribble’s proteins 1 mediated macrophage polarization

description: Aggravated liver injury has been reported in aged ischemia/reperfusion-stressed livers; however, the mechanism of aged macrophage inflammatory regulation is not well understood. Here, we found that the adaptor protein TRIB1 plays a critical role in the differentiation of macrophages and the inflammatory response in the liver after ischemia/reperfusion injury. In the present study, we determined that aging promoted macrophage-mediated liver injury and that inflammation was mainly responsible for lower M2 polarization in liver transplantation-exposed humans post I/R. Young and aged mice were subjected to hepatic I/R modeling and showed that aging aggravated liver injury and suppressed macrophage TRIB1 protein expression and anti-inflammatory function in I/R‐stressed livers. Restoration of TRIB1 is mediated by lentiviral infection-induced macrophage anti-inflammatory M2 polarization and alleviated hepatic I/R injury. Moreover, TRIB1 overexpression in macrophages facilitates M2 polarization and anti-inflammation by activating MEK1-ERK1/2 signaling under IL-4 stimulation. Taken together, our results demonstrated that aging promoted hepatic I/R injury by suppressing TRIB1-mediated MEK1-induced macrophage M2 polarization and anti-inflammatory function.
DOI: 10.6084/m9.figshare.21952762
title: CircRNA hsa_circ_0070659 predicts poor prognosis and promotes non-small cell lung cancer (NSCLC) progression via microRNA-377 (miR-377) / Ras-Associated Binding Protein 3C (RAB3C) pathway

description: A large number of circular RNAs (circRNAs) are dysregulated in lung cancer and affect the progression and prognosis of lung disease. Herein, this study selected specific circular RNA (circ_0070659) by bioinformatics analysis and aimed to investigate the role of circ_0070659 in non-small cell lung cancer (NSCLC). The differentially expressed circRNA (hsa_circ_0070659) in NSCLC was screened from public databases (GEO), and real-time quantitative polymerase chain reaction (RT-qPCR) was carried out to identify the circ_0070659 levels in cancer tissues and cells. NSCLC cell proliferation, migration, and invasion abilities after circ_0070659 silencing was detected by colony formation assay, Cell Counting Kit-8 (CCK-8) assay and Transwell assay. Targeted binding between microRNA-377 (miR-377) and circ_0070659 or Ras-Associated Binding Protein 3C (RAB3C) was verified by western blot, dual-luciferase reporter assay, and RNA pull-down assay. Our experimental results showed that circ_0070659 levels were largely increased in tumor tissues and cells. Biologically, knockdown of circ_0070659 obviously inhibited proliferation, migration, and invasion of NSCLC cells. Mechanistically, circ_0070659 promoted RAB3C-mediated proliferation and invasion through sponging miR-377. Furthermore, miR-377 inhibitor reversed the inhibitory ability of circ_0070659 silencing on malignant biological behavior of NSCLC cells. Our study revealed a novel signaling pathway that circ_0070659/miR-377/RAB3C axis regulates tumor progression, and it may become a new therapeutic target for NSCLC.
DOI: 10.17026/ar/qxlvor
title: OM-11 Oude Maas: IVO-Underwater Evaluation Report

description: &lt;p&gt;Trident Archaeology was commissioned by WSP to carry out an IVO underwater evaluation (protocol 4103) of OM-11, an anomaly that had been highlighted as of possible archaeological interest located in the Oude Maas, along Hongerlandsedijk, Spijkenisse.&lt;/p&gt;&lt;p&gt;

The site is a clay mound measuring roughly 4 by 2 meters with irregular edges that rises approximately 0.3 meters above the river-bed. The materials found at the location included natural wood (tree stumps and raw wood), a small number of processed timbers (two posts and two boards), modern waste, a limited number of pottery fragments that date from the late medieval period, five fragments of clay pipe stems, five fragments of animal bones, and fragments of bricks. The variety and composition of the assemblage together with the fact that the finds were recovered from a mobile superficial sandy layer seems to indicate that this is a natural feature that acted as a trap for various debris carried downstream by the river rather than a feature of archaeological interest.&lt;/p&gt;
DOI: 10.6084/m9.figshare.20158569
title: N(6)-methyladenosine-mediated miR-380-3p maturation and upregulation promotes cancer aggressiveness in pancreatic cancer

description: N(6)-methyladenosine (m6A)-modified microRNAs (miRNAs) are relevant to cancer progression. Also, although the involvement of miR-380-3p in regulating cancer progression in bladder cancer and neuroblastoma has been preliminarily explored, its role in other types of cancer, such as pancreatic cancer (PC), has not been studied. Thus, this study aimed to investigate the role of miR-380-3p in regulating PC progression. Here, through performing Real-Time qPCR, we evidenced that miR-380-3p was significantly upregulated in the clinical pancreatic cancer tissues and cells compared to their normal counterparts. Interestingly, miR-380-3p was enriched with m6A modifications, and elimination of m6A modifications by deleting METTL3 and METTL14 synergistically suppressed miR-380-3p expressions in PC cells. Next, the gain and loss-of-function experiments verified that knockdown of miR-380-3p suppressed cell proliferation, epithelial–mesenchymal transition (EMT), and tumorigenesis in PC cells <i>in vitro</i> and <i>in vivo</i>, whereas miR-380-3p overexpression had opposite effects. Furthermore, the underlying mechanisms were uncovered, and our data suggested that miR-380-3p targeted the 3’ untranslated regions (3ʹUTRs) of PTEN for its inhibition and degradation, resulting in the activation of the downstream Akt signal pathway. Moreover, the rescuing experiments validated that both PTEN overexpression and Akt pathway inhibitor LY294002 abrogated the promoting effects of miR-380-3p overexpression on cancer aggressiveness in PC cells. Collectively, this study firstly investigated the role of the m6A-associated miR-380-3p/PTEN/Akt pathway in regulating PC progression, which provided novel therapeutic and diagnostic biomarkers for this cancer.
DOI: 10.6084/m9.figshare.20158569.v1
title: N(6)-methyladenosine-mediated miR-380-3p maturation and upregulation promotes cancer aggressiveness in pancreatic cancer

description: N(6)-methyladenosine (m6A)-modified microRNAs (miRNAs) are relevant to cancer progression. Also, although the involvement of miR-380-3p in regulating cancer progression in bladder cancer and neuroblastoma has been preliminarily explored, its role in other types of cancer, such as pancreatic cancer (PC), has not been studied. Thus, this study aimed to investigate the role of miR-380-3p in regulating PC progression. Here, through performing Real-Time qPCR, we evidenced that miR-380-3p was significantly upregulated in the clinical pancreatic cancer tissues and cells compared to their normal counterparts. Interestingly, miR-380-3p was enriched with m6A modifications, and elimination of m6A modifications by deleting METTL3 and METTL14 synergistically suppressed miR-380-3p expressions in PC cells. Next, the gain and loss-of-function experiments verified that knockdown of miR-380-3p suppressed cell proliferation, epithelial–mesenchymal transition (EMT), and tumorigenesis in PC cells <i>in vitro</i> and <i>in vivo</i>, whereas miR-380-3p overexpression had opposite effects. Furthermore, the underlying mechanisms were uncovered, and our data suggested that miR-380-3p targeted the 3’ untranslated regions (3ʹUTRs) of PTEN for its inhibition and degradation, resulting in the activation of the downstream Akt signal pathway. Moreover, the rescuing experiments validated that both PTEN overexpression and Akt pathway inhibitor LY294002 abrogated the promoting effects of miR-380-3p overexpression on cancer aggressiveness in PC cells. Collectively, this study firstly investigated the role of the m6A-associated miR-380-3p/PTEN/Akt pathway in regulating PC progression, which provided novel therapeutic and diagnostic biomarkers for this cancer.
DOI: 10.6084/m9.figshare.20156133
title: Ibuprofen promotes p75 neurotrophin receptor expression through modifying promoter methylation and N6-methyladenosine-RNA-methylation in human gastric cancer cells

description: It is acknowledged that nonsteroidal anti-inflammatory drugs (NSAIDs) can participate in various signaling pathways, while information about their epigenetic effects are limited. p75NTR (p75 neurotrophin receptor) can inhibit tumor growth by inducing cell cycle arrest and regulating cell cycle arrest and apoptotic cell death. The expression of p75NTR is influenced by epigenetic roles. We explored the effects of ibuprofen on p75NTR expression and investigated whether promoter methylation and N6-methyladenosine (m6A) RNA methylation regulates this process in human gastric cancer cells (SGC7901 and MKN45). Cell lines were treated with ibuprofen 0, 2.5, 5, 10, 20 µM, and then DNA, RNA, and protein were isolated 24 h later. Expression and promoter methylation of p75NTR were detected by RT-qPCR and Western blot. The levels of m6A-p75NTR were measured by RNA immunoprecipitation. We also used RT-qPCR to determine the levels of m6A-related regulators, METTL3, METTL14, ALKBH5, FTO, YTHDC2, and YTHDF1-3. Ibuprofen attenuated p75NTR promoter methylation (<i>p</i> &lt; 0.01) and increased p75NTR level (<i>p</i> &lt; 0.001). Ibuprofen increased m6A-p53 expression (<i>p</i> &lt; 0.01) by promoting the expression of METTL3 (<i>p</i> &lt; 0.01) and METTL14 (<i>p</i> &lt; 0.05); and increased levels of YTHDF1 (<i>p</i> &lt; 0.001), YTHDF3 (<i>p</i> &lt; 0.001), and YTHDC2 (<i>p</i> &lt; 0.01) that finally reinforced p53 translation (<i>p</i> &lt; 0.01). Therefore, our results present that ibuprofen epigenetically increased p75NTR expression by downregulating promoter methylation and upregulating m6A-RNA-methylation in SGC7901 and MKN45 cells. Our study unveils a novel mechanism for p75NTR regulation by NSAIDs and helps the design of treatment targets.
DOI: 10.6084/m9.figshare.20156133.v1
title: Ibuprofen promotes p75 neurotrophin receptor expression through modifying promoter methylation and N6-methyladenosine-RNA-methylation in human gastric cancer cells

description: It is acknowledged that nonsteroidal anti-inflammatory drugs (NSAIDs) can participate in various signaling pathways, while information about their epigenetic effects are limited. p75NTR (p75 neurotrophin receptor) can inhibit tumor growth by inducing cell cycle arrest and regulating cell cycle arrest and apoptotic cell death. The expression of p75NTR is influenced by epigenetic roles. We explored the effects of ibuprofen on p75NTR expression and investigated whether promoter methylation and N6-methyladenosine (m6A) RNA methylation regulates this process in human gastric cancer cells (SGC7901 and MKN45). Cell lines were treated with ibuprofen 0, 2.5, 5, 10, 20 µM, and then DNA, RNA, and protein were isolated 24 h later. Expression and promoter methylation of p75NTR were detected by RT-qPCR and Western blot. The levels of m6A-p75NTR were measured by RNA immunoprecipitation. We also used RT-qPCR to determine the levels of m6A-related regulators, METTL3, METTL14, ALKBH5, FTO, YTHDC2, and YTHDF1-3. Ibuprofen attenuated p75NTR promoter methylation (<i>p</i> &lt; 0.01) and increased p75NTR level (<i>p</i> &lt; 0.001). Ibuprofen increased m6A-p53 expression (<i>p</i> &lt; 0.01) by promoting the expression of METTL3 (<i>p</i> &lt; 0.01) and METTL14 (<i>p</i> &lt; 0.05); and increased levels of YTHDF1 (<i>p</i> &lt; 0.001), YTHDF3 (<i>p</i> &lt; 0.001), and YTHDC2 (<i>p</i> &lt; 0.01) that finally reinforced p53 translation (<i>p</i> &lt; 0.01). Therefore, our results present that ibuprofen epigenetically increased p75NTR expression by downregulating promoter methylation and upregulating m6A-RNA-methylation in SGC7901 and MKN45 cells. Our study unveils a novel mechanism for p75NTR regulation by NSAIDs and helps the design of treatment targets.
DOI: 10.6084/m9.figshare.21821140
title: Easy efficient HDR-based targeted knock-in in <i>Saccharomyces cerevisiae</i> genome using CRISPR-Cas9 system

description: During the last two decades, yeast has been used as a biological tool to produce various small molecules, biofuels, etc., using an inexpensive bioprocess. The application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated protein (Cas) techniques in yeast genetic and metabolic engineering has made a paradigm shift, particularly with a significant improvement in targeted chromosomal integration using synthetic donor constructs, which was previously a challenge. This study reports the CRISPR-Cas9-based highly efficient strategy for targeted chromosomal integration and in-frame expression of a foreign gene in the genome of <i>Saccharomyces cerevisiae</i> (<i>S. cerevisiae</i>) by homology-dependent recombination (HDR); our optimized methods show that CRISPR-Cas9-based chromosomal targeted integration of small constructs at multiple target sites of the yeast genome can be achieved with an efficiency of 74%. Our study also suggests that 15 bp microhomology flanked arms are sufficient for 50% targeted knock-in at minimal knock-in construct concentration. Whole-genome sequencing confirmed that there is no off-target effect. This study provides a comprehensive and streamlined protocol that will support the targeted integration of essential genes into the yeast genome for synthetic biology and other industrial purposes. <b>Highlights</b> <b>•</b> CRISPR-Cas9 based in-frame expression of foreign protein in <i>Saccharomyces cerevisiae</i> using Homology arm without a promoter. <b>•</b> As low as 15 base pairs of microhomology (HDR) are sufficient for targeted integration in <i>Saccharomyces cerevisiae</i>. <b>•</b> The methodology is highly efficient and very specific as no off-targeted effects were shown by the whole-genome sequence.
DOI: 10.6084/m9.figshare.21821140.v1
title: Easy efficient HDR-based targeted knock-in in <i>Saccharomyces cerevisiae</i> genome using CRISPR-Cas9 system

description: During the last two decades, yeast has been used as a biological tool to produce various small molecules, biofuels, etc., using an inexpensive bioprocess. The application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated protein (Cas) techniques in yeast genetic and metabolic engineering has made a paradigm shift, particularly with a significant improvement in targeted chromosomal integration using synthetic donor constructs, which was previously a challenge. This study reports the CRISPR-Cas9-based highly efficient strategy for targeted chromosomal integration and in-frame expression of a foreign gene in the genome of <i>Saccharomyces cerevisiae</i> (<i>S. cerevisiae</i>) by homology-dependent recombination (HDR); our optimized methods show that CRISPR-Cas9-based chromosomal targeted integration of small constructs at multiple target sites of the yeast genome can be achieved with an efficiency of 74%. Our study also suggests that 15 bp microhomology flanked arms are sufficient for 50% targeted knock-in at minimal knock-in construct concentration. Whole-genome sequencing confirmed that there is no off-target effect. This study provides a comprehensive and streamlined protocol that will support the targeted integration of essential genes into the yeast genome for synthetic biology and other industrial purposes. <b>Highlights</b> <b>•</b> CRISPR-Cas9 based in-frame expression of foreign protein in <i>Saccharomyces cerevisiae</i> using Homology arm without a promoter. <b>•</b> As low as 15 base pairs of microhomology (HDR) are sufficient for targeted integration in <i>Saccharomyces cerevisiae</i>. <b>•</b> The methodology is highly efficient and very specific as no off-targeted effects were shown by the whole-genome sequence.
DOI: 10.6084/m9.figshare.21952765
title: Exosomes derived from fibrinogen-like protein 1-overexpressing bone marrow-derived mesenchymal stem cells ameliorates rheumatoid arthritis

description: Rheumatoid arthritis (RA) is a most common chronic joint disease belonging to inflammatory autoimmune disease. The aim of this study was to determine the role and mechanism of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes and fibrinogen-like protein 1 (FGL1) overexpression exosomes shuttled by BMSCs (FGL1-Exos) on RA. All of the exosomes were visualized by transmission electron microscope (TEM) and the characteristic proteins were detected by western blot. To investigate the therapeutic effect of FGL1-Exos, RA-FLSs were activated by TNF-α and RA rat model was established by collagen incomplete Freund’s adjuvant. Cell viability, apoptosis, inflammation factors, and protein levels were detected by CCK-8, flow cytometry, enzyme-linked immunosorbent assay and western blot, respectively. Hematoxylin and eosin and safranin O staining were used to detect the histopathology changes. Cell apoptosis and FGL1 expression in knee joint were detected by immunofluorescence. The results showed that FGL1-Exos could inhibit the cell viability meanwhile increase the cell apoptosis in RA-FLSs. Meanwhile, FGL1-Exos could effectively suppress the inflammation score, joint destruction, and inflammatory response in RA rat model. FGL1-Exos directly inhibited cell apoptosis of RA-FLSs and RA rat model by suppressing the inflammatory cytokines, specific rheumatoid markers, immunological markers meanwhile meditating the NF-κB pathway. Our results indicate that FGL1 was a therapeutic potential target in RA therapy.
DOI: 10.6084/m9.figshare.21952765.v1
title: Exosomes derived from fibrinogen-like protein 1-overexpressing bone marrow-derived mesenchymal stem cells ameliorates rheumatoid arthritis

description: Rheumatoid arthritis (RA) is a most common chronic joint disease belonging to inflammatory autoimmune disease. The aim of this study was to determine the role and mechanism of bone marrow mesenchymal stem cells (BMSCs)-derived exosomes and fibrinogen-like protein 1 (FGL1) overexpression exosomes shuttled by BMSCs (FGL1-Exos) on RA. All of the exosomes were visualized by transmission electron microscope (TEM) and the characteristic proteins were detected by western blot. To investigate the therapeutic effect of FGL1-Exos, RA-FLSs were activated by TNF-α and RA rat model was established by collagen incomplete Freund’s adjuvant. Cell viability, apoptosis, inflammation factors, and protein levels were detected by CCK-8, flow cytometry, enzyme-linked immunosorbent assay and western blot, respectively. Hematoxylin and eosin and safranin O staining were used to detect the histopathology changes. Cell apoptosis and FGL1 expression in knee joint were detected by immunofluorescence. The results showed that FGL1-Exos could inhibit the cell viability meanwhile increase the cell apoptosis in RA-FLSs. Meanwhile, FGL1-Exos could effectively suppress the inflammation score, joint destruction, and inflammatory response in RA rat model. FGL1-Exos directly inhibited cell apoptosis of RA-FLSs and RA rat model by suppressing the inflammatory cytokines, specific rheumatoid markers, immunological markers meanwhile meditating the NF-κB pathway. Our results indicate that FGL1 was a therapeutic potential target in RA therapy.
DOI: 10.6084/m9.figshare.20156764.v2
title: Circular RNA_0078767 upregulates Kruppel-like factor 9 expression by targeting microRNA-889, thereby inhibiting the progression of osteosarcoma

description: Among kids and juveniles, osteosarcoma (OS) is a common bone malignancy. Circular RNAs (circs, circRNAs) play important roles in multiple malignancies including OS, yet circ_0078767ʹs biological functions in OS are far from well elucidated. This study is targeted at understanding circ_0078767ʹs biological functions in OS and its molecular mechanisms. This study confirmed that circ_0078767 expression was reduced in OS cell lines and tissues. Circ_0078767 overexpression remarkably inhibited OS cell growth, migration, invasion, epithelial-mesenchymal transition (EMT), and promoted apoptosis, whereas circ_0078767 knockdown resulted in the opposite effects. MicroRNA-889 (miR-889) was targeted and regulated by circ_0078767, and miR-889 could negatively modulate Kruppel-like factor 9 (KLF9) expression. Besides, circ_0078767 positively regulated KLF9 expression in OS cells via repressing miR-889. In conclusion, circ_0078767 enhances KLF9 expression by targeting miR-889 to inhibit OS progression.