Jonesfanning3804

Collectively, the present study revealed that Oroxylin A exerted marked anticancer effects against ovarian cancer in vitro. Thus, Oroxylin A may have potential for use as a complementary therapy in the treatment of ovarian cancer.Single‑cell RNA sequencing (scRNA‑seq) of bone marrow or peripheral blood samples from patients with acute myeloid leukemia (AML) enables the characterization of heterogeneous malignant cells. A total of 87 cells from two patients with t(8;21) AML were analyzed using scRNA‑seq. Clustering methods were used to separate leukemia cells into different sub‑populations, and the expression patterns of specific marker genes were used to annotate these populations. Among the 31 differentially expressed genes in the cells of a patient who relapsed after hematopoietic stem cell transplantation, 13 genes were identified to be associated with leukemia. Furthermore, three genes, namely AT‑rich interaction domain 2, lysine methyltransferase 2A and synaptotagmin binding cytoplasmic RNA interacting protein were validated as possible prognostic biomarkers using two bulk expression datasets. Taking advantage of scRNA‑seq, the results of the present study may provide clinicians with several possible biomarkers to predict the prognostic outcomes of t(8;21) AML.Osteosarcoma (OS) is a common malignant bone tumor, presenting particularly in children and young adults, and accounts for approximately 19% of all malignant bone cancers. Despite advances in OS treatment, long‑term prognosis remains poor. miRNAs are non‑coding single‑stranded RNAs ~22 nucleotides in length. Increasing evidence suggests that numerous miRNAs may play critical roles in tumorigenesis and tumor progression; however, the role of miR‑95 in OS has not been examined. In the present study, we investigated the role of miR‑95 in OS using in vitro and in vivo models and publicly available expression data. Our findings indicate that abnormal miR‑95 expression occurs in OS, according to the Gene Expression Omnibus (GEO) database. The miR‑95 inhibitor reduced cell proliferation and promoted apoptosis in OS cell lines as detected by EdU staining, TUNEL staining and flow cytometry. Furthermore, a dual luciferase reporter assay revealed that miR‑95 regulates the cell cycle of OS cells and apoptosis by targeting sodium channel epithelial 1α subunit (SCNN1A). Additionally, miR‑95 antagomir suppressed the growth of U2OS xenograft tumors in a mouse model. In summary, our results suggest that miR‑95 induces OS growth in vitro and in vivo by targeting SCNN1A. Our results help clarify the mechanism underlying the miR‑95‑mediated effects on OS tumor growth, thus potentially establishing it as a diagnostic target.Long non‑coding RNAs (lncRNAs) are involved in colorectal cancer (CRC) progression, however the mechanisms remain largely unknown. The present study aimed to reveal the role and possible molecular mechanisms of a new LNCRNA, LINC00858, in CRC. selleck LINC00858 was increased in CRC tumor tissues, and patients with high LINC00858 expression had a shorter survival time. Knockdown of LINC00858 expression suppressed cell proliferation and induced G0/G1 cell cycle arrest and apoptosis in TP53‑wild‑type CRC cells. Subsequently, using Starbase v2.0 database, miR‑25‑3p was confirmed to interact with LINC00858 and was downregulated by LINC00858. Reduction of miR‑25‑3p expression with an inhibitor significantly attenuated the biological effects of LINC00858 knockdown in CRC cells. Furthermore, using TargetScan, SMAD7 was validated to interact with miR‑25‑3p and was downregulated by miR‑25‑3p. Lastly, the ectopic overexpression of SMAD7 rescued the suppressive effects of LINC00858 knockdown in CRC cells. Collectively, the results from the present study, to the best of our knowledge, firstly demonstrated a novel LINC00858/miR‑25‑3p/SMAD7 regulatory axis that promoted CRC progression, indicating LINC00858 as a promising therapeutic target for CRC.Melatonin secreted by the pineal body is associated with the occurrence and development of idiopathic scoliosis. Melatonin has a concentration‑dependent dual effect on osteoblast proliferation, in which higher concentrations can inhibit osteoblast proliferation and induce apoptosis; however, the underlying mechanism remains unclear. In the present study, flow cytometry was used to demonstrate that osteoblast cells treated with melatonin exhibited significantly increased early and late stage apoptotic rates as the concentration increased. Chromatin condensation in the nucleus and apoptotic body formation could be observed using fluorescent microscopy in osteoblast cells treated with 2 mM melatonin. Western blotting results showed that there was an upregulation in the expression of apoptosis marker proteins [poly (ADP‑ribose) polymerase 1 (PARP‑1)], endoplasmic reticulum stress [ERS; C/EBP homologous protein (CHOP) and glucose‑regulated protein, 78 kDa (GRP78)] and autophagy [microtubule‑associated protein 1 light chain 3β (LC3)‑I/LC3II]. PARP‑1 expression was not altered when treated with ERS inhibitor 4PBA and autophagy inhibitor 3MA, whereas 4PBA or 3MA in combination with 2 mM melatonin (or the three together) significantly increased PARP‑1 expression. Furthermore, the use of septin7 small interfering RNA confirmed that increased expression of GRP78 and CHOP was related to septin7, and melatonin‑​mediated ERS was necessary for septin7 activation. These findings suggest that ERS and autophagy might occur in the early stage of treatment with a high concentration of melatonin, and each might play a protective role in promoting survival; in a later stage, ERS and autophagy might interact and contribute to the induction of apoptosis. Overall, the results indicated that septin7 may be a target protein of melatonin‑induced ERS.Cathepsin A (CTSA) is a lysosomal protease that is abnormally expressed in various types of cancer; however, the function of CTSA in lung adenocarcinoma (LUAD) is unknown. The aim of the present study was to investigate the role of CTSA during LUAD development in vitro. The Cancer Genome Atlas (TCGA) database was used to analyze the expression of CTSA mRNA in LUAD tissues. CTSA was significantly upregulated in LUAD tissues compared with normal lung tissues. To explore the effect of CTSA on LUAD in vitro, LUAD A549 cells were transfected with CTSA small interfering RNA and the hallmarks of tumorigenesis were investigated using cell proliferation, cell cycle, wound healing, invasion and western blot assays. Following CTSA knockdown, proliferation of LUAD cells was decreased and an increased proportion of LUAD cells were arrested at the G0/G1 phase, with altered expression of critical cell cycle and proliferative marker proteins, including p53, p21 and proliferating cell nuclear antigen. Moreover, CTSA knockdown decreased the migration and invasion of A549 cells, as determined by wound healing, invasion, and western blotting assays. The expression levels of key proteins involved in epithelial‑mesenchymal transition were analyzed by western blotting. CTSA knockdown enhanced the expression of E‑cadherin, but decreased the expression of N‑cadherin and β‑catenin in A549 cells. To the best of our knowledge, the present study suggested for the first time it has been identified that CTSA may serve as a tumor promoter in LUAD, enhancing the malignant progression of LUAD cells by promoting cell proliferation, migration and invasion. The results suggested that CTSA may serve as a novel therapeutic target for LUAD.The PTEN induced putative kinase 1 (PINK1) mutation is the second most common cause of autosomal recessive adolescent Parkinson's disease (PD). Furthermore, mitochondrial disorders and oxidative stress are important mechanisms in the pathogenesis of PD. Numerous members of the Wnt family have been found to be associated with neurodegenerative diseases. Therefore, the present study investigated the role of the Wnt2 gene in PINK1B9 transgenic flies, which is a PD model, and its underlying mechanism. It was identified that overexpression of Wnt2 reduced the abnormality rate of PD transgenic Drosophila and improved their flight ability, while other intervention groups had no significant effect. Furthermore, an increase in ATP concentration normalized mitochondrial morphology, and increased the mRNA expression levels of NADH‑ubiquinone oxidoreductase chain 1 (ND1), ND42, ND75, succinate dehydrogenase complex subunits B, Cytochrome b and Cyclooxygenase 1, which are associated with Wnt2 overexpression. Moreover, overexpression of Wnt2 in PD transgenic Drosophila resulted in the downregulation of reactive oxygen species and malondialdehyde production, and increased manganese superoxide dismutase (MnSOD), while glutathione was not significantly affected. It was found that overexpression of Wnt2 did not alter the protein expression of β‑catenin in PINK1B9 transgenic Drosophila, but did increase the expression levels of PPARG coactivator 1α (PGC‑1α) and forkhead box sub‑group O (FOXO). Collectively, the present results indicated that the Wnt2 gene may have a protective effect on PD PINK1B9 transgenic Drosophila. Thus, it was speculated that the reduction of oxidative stress and the restoration of mitochondrial function via Wnt2 overexpression may be related to the PGC‑1α/FOXO/MnSOD signaling pathway in PINK1 mutant transgenic Drosophila.Pancreatic encephalopathy (PE) is a common fatal complication of acute pancreatitis (AP). Proinflammatory cytokines such as tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 are generated during AP, and act synergistically to promote PE and multisystem failure. Caerulein‑induced AP provides a convenient model to explore the role of proinflammatory cytokines in PE. The aim of the present study was to examine the effect of the TNF‑α inhibitor etanercept in PE models and elucidate the regulatory mechanisms. To model PE in vitro, rat hippocampal H19‑7/IGF‑IR neuronal cells were treated with 10 nmol/ml caerulein alone or in combination with etanercept (1, 10 or 100 µmol/ml). To model PE in vivo, rats were injected with 50 µg/kg caerulein alone or combined with 10 mg/kg etanercept. At 6 h after administration, it was noted that etanercept downregulated expression of TNF‑α, IL‑1β and IL‑6 by negatively regulating NF‑κB (a master regulator of cytokine expression) signaling, and prevented the accumulation of reactive oxygen species. Conversely, etanercept promoted the expression of the neurotrophic and anti‑inflammatory hypoxia‑inducible factor 1 α (HIF‑1α). In rat hippocampus, etanercept also reduced the levels of TNF‑α, IL‑1β and IL‑6, upregulated HIF‑1α expression and inhibited the inflammatory response to reduce edema and neural necrosis. Together, these data suggested that etanercept could attenuate caerulein‑induced PE, at least in part via suppression of NF‑κB signaling and alleviation of oxidative stress.Ewing sarcoma (ES) is a primary bone marrow tumor that very rarely develops in extra‑osseous tissues, such as lung. The hallmark of ES tumors is a translocation between chromosomes 11 and 22, resulting in a fusion protein, commonly referred to as EWS‑FLI1. The epigenetic profile (histone acetylation and methylation enrichment of the promoter region) that may regulate the expression of the aberrant transcription factor EWS‑FLI1, remains poorly studied and understood. Knowledge of epigenetic patterns associated with covalent histone modification and expression of enzymes associated with this process, can contribute to the understanding of the molecular basis of the disease, as well as to the identification of possible molecular targets involved in expression of the EWS‑FLI1 gene, so that therapeutic strategies may be improved in the future. In the present study, the transcriptional activation and repression of the EWS‑FLI1 fusion gene in ES was accompanied by selective deposition of histone markers on its promoter.