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BMC Ophthalmology Jun 2024The purpose of this study was to investigate the photoprotection effect of peroxiredoxin 1 (PRDX1) protein in ultraviolet B (UVB) irradiation-induced damage of retinal...
BACKGROUND
The purpose of this study was to investigate the photoprotection effect of peroxiredoxin 1 (PRDX1) protein in ultraviolet B (UVB) irradiation-induced damage of retinal pigment epithelium (RPE) and its possible molecular mechanism.
METHODS
ARPE-19 cell viability and apoptosis were assessed by MTT assay and flow cytometry, respectively. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the PRDX1 expression. The corresponding kits were employed to measure the levels or activities of lactate dehydrogenase (LDH), 8-hydroxy-2-deoxyguanosine (8-OHdG), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD). Western blotting was applied to examine PRDX1 expression and mitogen-activated protein kinase (MAPK) signaling pathway-related proteins.
RESULTS
After exposure to 20 mJ/cm intensity of UVB irradiation for 24 h, ARPE-19 cells viability was decreased, the leakage degree of LDH and 8-OHdG were increased, and cell apoptosis was elevated. The expression of PRDX1 was significantly down-regulated in UVB-induced ARPE-19 cells. The low expression of PRDX1 was involved in high irradiation intensity. Overexpression of PRDX1 increased cell activity, decreased cell apoptosis, and LDH as well as 8-OHdG leakage in UVB-induced ARPE-19 cells. In addition to alleviating UVB-induced cell damage, PRDX1 overexpression also inhibited UVB-induced oxidative stress (down-regulation of ROS and MDA levels, up-regulation of GSH-Px and SOD activities) and the activation of MAPK signaling pathway in ARPE-19 cells.
CONCLUSION
PRDX1 exerts a photoprotection effect on RPE by attenuating UVB-induced cell damage and inhibiting oxidative stress, which can be attributed to the inhibition of MAPK signaling pathway activation.
Topics: Humans; Oxidative Stress; Retinal Pigment Epithelium; Peroxiredoxins; Ultraviolet Rays; Cell Survival; Apoptosis; Reactive Oxygen Species; MAP Kinase Signaling System; Cell Line; Blotting, Western; Cells, Cultured; 8-Hydroxy-2'-Deoxyguanosine; Signal Transduction
PubMed: 38844903
DOI: 10.1186/s12886-024-03489-4 -
Nature Communications Jun 2024Neuronal differentiation requires building a complex intracellular architecture, and therefore the coordinated regulation of defined sets of genes. RNA-binding proteins...
Neuronal differentiation requires building a complex intracellular architecture, and therefore the coordinated regulation of defined sets of genes. RNA-binding proteins (RBPs) play a key role in this regulation. However, while their action on individual mRNAs has been explored in depth, the mechanisms used to coordinate gene expression programs shaping neuronal morphology are poorly understood. To address this, we studied how the paradigmatic RBP IMP1 (IGF2BP1), an essential developmental factor, selects and regulates its RNA targets during the human neuronal differentiation. We perform a combination of system-wide and molecular analyses, revealing that IMP1 developmentally transitions to and directly regulates the expression of mRNAs encoding essential regulators of the microtubule network, a key component of neuronal morphology. Furthermore, we show that m6A methylation drives the selection of specific IMP1 mRNA targets and their protein expression during the developmental transition from neural precursors to neurons, providing a molecular principle for the onset of target selectivity.
Topics: Humans; RNA-Binding Proteins; Microtubules; Neurons; Cell Differentiation; RNA, Messenger; Methylation; Neurogenesis; Adenosine; Gene Expression Regulation, Developmental
PubMed: 38844464
DOI: 10.1038/s41467-024-49139-7 -
International Journal of Cardiology Sep 2024no-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and... (Comparative Study)
Comparative Study
BACKGROUND
no-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and verapamil with intracoronary adenosine in the treatment of no-reflow after primary percutaneous coronary intervention (pPCI).
METHODS
108 STEMI patients had no-reflow during pPCI were assigned into four groups. Group 1, in which epinephrine and verapamil were injected through a well-cannulated guiding catheter. Group 2, in which same drugs were injected in the distal coronary bed through a microcatheter or perfusion catheter. Group 3, in which adenosine was injected through a guiding catheter. Group 4, in which adenosine was injected in distal coronary bed. Primary end point was the achievement of TIMI III flow and MBG II or III. Secondary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during hospital stay.
RESULTS
The study groups did not differ in their baseline characteristics. Primary end point was achieved in 15 (27.8%) patients in the guide-delivery arm compared with 34 (63%) patients in the local-delivery arm, p < 0.01. However, the primary end point did not differ between the epinephrine/verapamil group and the adenosine group (27 (50%) vs 22 (40.7%), p = 0.334). The secondary end points were similar between the study groups.
CONCLUSION
Local delivery of epinephrine, verapamil and adenosine in the distal coronary bed is more effective in achieving TIMI III flow with MBG II or III compared with their guide-delivery in patients who suffered no-reflow during pPCI. There was no difference between epinephrine/verapamil Vs. adenosine.
Topics: Humans; Verapamil; Male; Female; Adenosine; Epinephrine; Middle Aged; Percutaneous Coronary Intervention; No-Reflow Phenomenon; ST Elevation Myocardial Infarction; Aged; Vasodilator Agents; Treatment Outcome; Prospective Studies
PubMed: 38844092
DOI: 10.1016/j.ijcard.2024.132228 -
PLoS Pathogens Jun 2024Although lack of ADAR (adenosine deaminase acting on RNA) orthologs, genome-wide A-to-I editing occurs specifically during sexual reproduction in a number of filamentous... (Review)
Review
Although lack of ADAR (adenosine deaminase acting on RNA) orthologs, genome-wide A-to-I editing occurs specifically during sexual reproduction in a number of filamentous ascomycetes, including Fusarium graminearum and Neurospora crassa. Unlike ADAR-mediated editing in animals, fungal A-to-I editing has a strong preference for hairpin loops and U at -1 position, which leads to frequent editing of UAG and UAA stop codons. Majority of RNA editing events in fungi are in the coding region and cause amino acid changes. Some of these editing events have been experimentally characterized for providing heterozygote and adaptive advantages in F. graminearum. Recent studies showed that FgTad2 and FgTad3, 2 ADAT (adenosine deaminase acting on tRNA) enzymes that normally catalyze the editing of A34 in the anticodon of tRNA during vegetative growth mediate A-to-I mRNA editing during sexual reproduction. Stage specificity of RNA editing is conferred by stage-specific expression of short transcript isoforms of FgTAD2 and FgTAD3 as well as cofactors such as AME1 and FIP5 that facilitate the editing of mRNA in perithecia. Taken together, fungal A-to-I RNA editing during sexual reproduction is catalyzed by ADATs and it has the same sequence and structural preferences with editing of A34 in tRNA.
Topics: RNA Editing; Adenosine Deaminase; Fungal Proteins; Ascomycota; RNA, Fungal; Adenosine; Inosine; Fusarium; Neurospora crassa
PubMed: 38843141
DOI: 10.1371/journal.ppat.1012238 -
JACC. Cardiovascular Interventions Jun 2024
Topics: Humans; Ticagrelor; Clopidogrel; Platelet Aggregation Inhibitors; Percutaneous Coronary Intervention; Treatment Outcome; Purinergic P2Y Receptor Antagonists; Risk Factors; Hemorrhage; Chronic Disease; Blood Platelets; Evidence-Based Medicine
PubMed: 38842998
DOI: 10.1016/j.jcin.2024.04.038 -
JACC. Cardiovascular Interventions Jun 2024Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Whether ticagrelor may reduce periprocedural myocardial necrosis after elective percutaneous coronary intervention (PCI) in patients with and without chronic clopidogrel therapy is unclear.
OBJECTIVES
This study sought to compare ticagrelor vs clopidogrel in patients with and without chronic clopidogrel therapy before undergoing elective PCI.
METHODS
In this prespecified analysis of the ALPHEUS (Assessment of Loading With the P2Y12 Inhibitor Ticagrelor or Clopidogrel to Halt Ischemic Events in Patients Undergoing Elective Coronary Stenting) trial, patients were defined as clopidogrel(+) and clopidogrel(-) according to the presence and absence of clopidogrel treatment for ≥7 days before PCI, respectively. The primary endpoint was the composite of PCI-related myocardial infarction and major injury as defined by the third and fourth universal definition 48 hours after PCI.
RESULTS
A total of 1,882 patients were included, 805 (42.7%) of whom were clopidogrel(+). These patients were older, had more comorbidities, and had more frequent features of complex PCI. The primary endpoint was less frequently present in clopidogrel(-) compared to clopidogrel(+) patients (32.8% vs 40.0%; OR: 0.73; 95% CI: 0.60-0.88), but no significant differences were reported for the risk of death, myocardial infarction, stroke, or transient ischemic attack at 48 hours or 30 days. Ticagrelor did not reduce periprocedural myocardial necrosis or the risk of adverse outcomes, and there was no significant interaction regarding the presence of chronic clopidogrel treatment.
CONCLUSIONS
Clopidogrel-naive patients presented less periprocedural complications compared to clopidogrel(+) patients, a difference related to a lower risk profile and less complex PCI. The absence of clopidogrel at baseline did not affect the absence of a difference between ticagrelor and clopidogrel in terms of PCI-related complications supporting the use of clopidogrel as the standard of care in elective PCI in patients with or without chronic clopidogrel treatment.
Topics: Humans; Clopidogrel; Ticagrelor; Percutaneous Coronary Intervention; Female; Male; Aged; Platelet Aggregation Inhibitors; Middle Aged; Treatment Outcome; Time Factors; Risk Factors; Myocardial Infarction; Chronic Disease; Purinergic P2Y Receptor Antagonists; Necrosis; Risk Assessment; Coronary Artery Disease; Stents; Hemorrhage
PubMed: 38842993
DOI: 10.1016/j.jcin.2024.04.015 -
Critical Reviews in Eukaryotic Gene... 2024RBM15 functions as an oncogene in multi-type cancers. However, the reports on the roles of RBM15 in cervical cancer are limited. The purpose of this study was to...
RBM15 functions as an oncogene in multi-type cancers. However, the reports on the roles of RBM15 in cervical cancer are limited. The purpose of this study was to investigate the potentials of RBM15 in cervical cancer. RT-qPCR was conducted to determine mRNA levels. Western was carried out to detect protein expression. CCK-8, colony formation and EdU assays were conducted to determine cell proliferation. Scratch and transwell assays were conducted to determine cell migration and invasion. MeRIP assay was conducted to determine N6-methyl adenosine (m6A) levels. Luciferase assay was conducted to verify the m6A sites of EZH2 and binding sites between EZH2 and promoter of FN1. ChIP assay was conducted to verify the interaction between EZH2 and FN1. The results showed that RBM15 was upregulated in cervical cancer patients and cells. Moreover, high levels of RBM15 predicted poor clinical outcomes. RBM15 knockdown inhibited the proliferation and epithelial-mesenchymal transition (EMT) of cervical cancer cells. RBM15 promoted the m6A modification of EZH2 as well as its protein translation. Additionally, EZH2 bound to the promoter of fibronectin 1 (FN1) and EZH2-FN1 axis is the cascade downstream of RBM15. Overexpressed EZH2 antagonized the effects of RBM15 knockdown and promoted the aggressiveness of cervical cancer cells. In summary, RBM15/EZH2/FN1 signaling cascade induces the proliferation and EMT of cervical cancer. Therefore, RBM15/EZH2/FN1 signaling may be a promising strategy for cervical cancer.
Topics: Humans; Uterine Cervical Neoplasms; Epithelial-Mesenchymal Transition; Enhancer of Zeste Homolog 2 Protein; Female; Adenosine; Cell Proliferation; RNA-Binding Proteins; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Cell Movement; Fibronectins
PubMed: 38842201
DOI: 10.1615/CritRevEukaryotGeneExpr.2024052205 -
Biological & Pharmaceutical Bulletin 2024Motile cilia in the ependymal cells that line the brain ventricles play pivotal roles in cerebrospinal fluid (CSF) flow in well-defined directions. However, the...
Motile cilia in the ependymal cells that line the brain ventricles play pivotal roles in cerebrospinal fluid (CSF) flow in well-defined directions. However, the substances and pathways which regulate their beating have not been well studied. Here, we used primary cultured cells derived from neonatal mouse brain that possess motile cilia and found that adenosine (ADO) stimulates ciliary beating by increasing the ciliary beat frequency (CBF) in a concentration-dependent manner, with the ED value being 5 µM. Ciliary beating stimulated by ADO was inhibited by A receptor (AR) antagonist MRS1754 without any inhibition by antagonists of other ADO receptor subtypes. The expression of AR on the cilia was also confirmed by immunofluorescence. The values of CBF were also increased by forskolin, which is an activator of adenylate cyclase, whereas they were not further increased by the addition of ADO. Furthermore, ciliary beating was not stimulated by ADO in the presence of a protein kinase A (PKA) inhibitors. These results altogether suggest that ADO stimulates ciliary beating through AR on the cilia, and activation of PKA.
Topics: Animals; Cilia; Receptor, Adenosine A2B; Cyclic AMP-Dependent Protein Kinases; Adenosine; Brain; Mice; Animals, Newborn; Cells, Cultured; Signal Transduction; Adenosine A2 Receptor Antagonists; Colforsin; Ependyma
PubMed: 38839362
DOI: 10.1248/bpb.b23-00913 -
Cancer Letters Aug 2024Long non-coding RNA (lncRNA) is closely related to a variety of human cancers, which may provide huge potential biomarkers for cancer diagnosis and treatment. However,...
Long non-coding RNA (lncRNA) is closely related to a variety of human cancers, which may provide huge potential biomarkers for cancer diagnosis and treatment. However, the aberrant expression of most lncRNAs in colorectal cancer (CRC) remains elusive. This study aims to explore the clinical significance and potential mechanism of lncRNA ABHD11 antisense RNA 1 (ABHD11-AS1) in the colorectal cancer. Here, we demonstrated that lncRNA ABHD11-AS1 is high-expressed in colorectal cancer (CRC) patients, and strongly related with poor prognosis. Functionally, ABHD11-AS1 suppresses ferroptosis and promotes proliferation and migration in CRC both in vitro and in vivo. Mechanically, lncRNA ABHD11-AS1 interacted with insulin-like growing factor 2 mRNA-binding protein 2 (IGF2BP2) to enhance FOXM1 stability, forming an ABHD11-AS1/FOXM1 positive feedback loop. E3 ligase tripartite motif containing 21 (TRIM21) promotes the degradation of IGF2BP2 via the K48-ubiquitin-lysosome pathway and ABHD11-AS1 promotes the interaction between IGF2BP2 and TRIM21 as scaffold platform. Furthermore, N -adenosine-methyltransferase-like 3 (METTL3) upregulated the stabilization of ABHD11-AS1 through the mA reader IGF2BP2. Our study highlights ABHD11-AS1 as a significant regulator in CRC and it may become a potential target in future CRC treatment.
Topics: Humans; Colorectal Neoplasms; Ferroptosis; RNA, Long Noncoding; Forkhead Box Protein M1; RNA-Binding Proteins; Ribonucleoproteins; Gene Expression Regulation, Neoplastic; Cell Proliferation; Animals; Mice; Feedback, Physiological; Disease Progression; Cell Line, Tumor; Male; Cell Movement; Female; Mice, Nude; Prognosis; Adenosine; Serine Proteases
PubMed: 38838765
DOI: 10.1016/j.canlet.2024.217004 -
Molecular Cell Jun 2024Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized and what roles they play during this process have remained elusive....
Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized and what roles they play during this process have remained elusive. Comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain (FB) neurons, we identify that a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon differentiation. Such a subcellular relocation of circRNAs is modulated by the poly(A)-binding protein PABPC1. In the H9 nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and trapped by the nuclear basket protein TPR to prevent their export. Modulating (A)-rich motifs in circRNAs alters their subcellular localization, and introducing (A)-rich circRNAs in H9 cytosols results in mRNA translation suppression. Moreover, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs, including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.
Topics: RNA, Circular; Neurons; Active Transport, Cell Nucleus; Adenosine; Cell Nucleus; Neurogenesis; Humans; Poly(A)-Binding Protein I; Animals; RNA; Cell Line; Cell Differentiation; Cytoplasm; Prosencephalon
PubMed: 38838666
DOI: 10.1016/j.molcel.2024.05.011