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Background: The marine gastropod mollusc Nassarius sinarum has attracted attention due to its status as a potential invasive species and the ecological impact it may have on local environments and the fishing industry. It was observed exclusively within China initially, but its distribution now seems to have expanded into Japan and Korea. Accurate identification of N. sinarum, particularly in its juvenile stage, is vital for understanding its ecological influences and distribution patterns. New information: This study represents the first comprehensive analysis of N. sinarum samples from Korea. It includes morphological examination, scanning electron microscopy images and molecular sequencing. Two live specimens were collected from the Yeongsan River estuary in Korea and their morphological features were analysed and compared to those of samples from China and Japan. The samples' species were confirmed by molecular identification, based on cytochrome c oxidase subunit I (COI) and histone H3 (H3) genetic markers.It was observed that juvenile N. sinarum shells lack key species-characteristic morphological traits, such as a thick outer lip and diminishing axial ribs. However, COI marker-based molecular identification affirmed that these Korean specimens were N. sinarum. The H3 region was registered with the National Center for Biotechnology Information (NCBI) for the first time. Phylogenetic analysis of the H3 region did not resolve species distinctions within the Nassarius, suggesting that the H3 marker is not suitable for species identification within this genus. In this context, multiple genetic markers, when used appropriately, can also be applied to genus-level searches, enhancing species identification accuracy and reducing misidentification.The sequences provided in this study can serve as a valuable reference for future DNA barcoding research. Additional samples and surveys should be conducted through collaborative efforts amongst national and institutional organisations to further clarify the ecological status of N. sinarum and to investigate its distribution and potential impact around East Asia. Finally, a new Korean name, (No-lan-jul-job-ssal-mu-nui-go-dung; ë ¸ëì¤ì¢ì무ë¬ê³ ë¥) has been proposed for N. sinarum.
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Background and Objectives: MYC, also known as an oncogenic reprogramming factor, is a multifunctional transcription factor that maintains induced pluripotent stem cells (iPSCs). Although MYC is frequently upregulated in various cancers and is correlated with a poor prognosis, MYC is downregulated and correlated with a good prognosis in lung adenocarcinoma. MYC and two other MYC family genes, MYCN and MYCL, have similar structures and could contribute to tumorigenic conversion both in vitro and in vivo. Methods and Results: We systematically investigated whether MYC family genes act as prognostic factors in various human cancers. We first evaluated alterations in the expression of MYC family genes in various cancers using the Oncomine and The Cancer Genome Atlas (TCGA) database and their mutation and copy number alterations using the TCGA database with cBioPortal. Then, we investigated the association between the expression of MYC family genes and the prognosis of cancer patients using various prognosis databases. Multivariate analysis also confirmed that co-expression of MYC/MYCL/MYCN was significantly associated with the prognosis of lung, gastric, liver, and breast cancers. Conclusions: Taken together, our results demonstrate that the MYC family can function not only as an oncogene but also as a tumor suppressor gene in various cancers, which could be used to develop a novel approach to cancer treatment.
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The availability of autologous adult stem cells is one of the essential prerequisites for human stem cell therapy. Urine-derived stem cells (USCs) are considered as desirable cell sources for cell therapy because donor-specific USCs are easily and non-invasively obtained from urine. Efficient isolation, expansion, and differentiation methods of USCs are necessary to increase their availability. Here, we developed a method for efficient isolation and expansion of USCs using Matrigel, and the rho-associated protein kinase (ROCK) inhibitor, Y-27632. The prepared USCs showed significantly enhanced migration, colony forming capacity, and differentiation into osteogenic or chondrogenic lineage. The USCs were successfully reprogramed into induced pluripotent stem cells (USC-iPSCs) and further differentiated into kidney organoid and hematopoietic progenitor cells (HPCs). Using flavonoid molecules, the isolation efficiency of USCs and the production of HPCs from the USC-iPSCs was increased. Taken together, we present an improved isolation method of USCs utilizing Matrigel, a ROCK inhibitor and flavonoids, and enhanced differentiation of USC-iPSC to HPC by flavonoids. These novel findings could significantly enhance the use of USCs and USC-iPSCs for stem cell research and further application in regenerative stem cell-based therapies.
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OCT4 is a master transcription factor that regulates the pluripotency of pluripotent stem cells and cancer stem cells along with other factors, including SOX2, KLF4, and C-MYC. Three different transcripts, OCT4A, OCT4B, and OCT4B1, are known to be generated by alternative splicing and eight OCT4 pseudogenes have been found in the human genome. Among them, we examined OCT4 and three pseudogenes (POU5F1P1, POU5F1P3, and POU5F1P4) because of their high expression possibility in cancer. In addition, previous studies indicated that OCT4 expression is augmented in cervical cancer and associated with poor prognosis, whereas OCT4 is down-regulated and correlated with good clinical outcomes in breast cancer. Because of these conflicting reports, we systematically evaluated whether expression of OCT4 and its pseudogenes can serve as oncogenic markers in various human cancers using the Oncomine database. Moreover, copy number alterations and mutations in OCT4 gene and its pseudogenes were analyzed using cBioPortal and the relationship between expression of OCT4 and pseudogenes and survival probability of cancer patients were explored using Kaplan-Meier plotter, OncoLnc, PROGgeneV2, and PrognoScan databases. Multivariate survival analysis was further conducted to determine the risk of the expression of the occurrence of OCT4 and its pseudogenes on certain cancer types using data from the Kaplan-Meier plotter. Overall, an association between expression of OCT4 and pseudogenes and cancer prognosis were established, which may serve as a therapeutic target for various human cancers.
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Reprogramação Celular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Fator 3 de Transcrição de Octâmero/genética , Pseudogenes/genética , Humanos , Fator 4 Semelhante a Kruppel , Mutação/genética , Taxa de Mutação , Fator 3 de Transcrição de Octâmero/metabolismo , Prognóstico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de SobrevidaRESUMO
For cancer gene therapy, cancer-specific over- expression of a therapeutic gene is required to reduce side effects derived from expression of the gene in normal cells. To develop such an expression vector, we searched for genes over-expressed and/or specifically expressed in cancer cells using bioinformatics and have selected genes coding for protein regulator of cytokinesis 1 (PRC1) and ribonuclease reductase 2 (RRM2) as candidates. Their cancer-specific expressions were confirmed in both breast cancer cell lines and patient tissues. We compared each promoter's cancer-specific activity in the breast normal and cancer cell lines using the luciferase gene as a reporter and confirmed cancer-specific expression of both PRC1 and RRM2 promoters. To test activities of these promoters in viral vectors, the promoters were also cloned into an adeno-associated viral (AAV) vector containing green fluorescence protein (GFP) as the reporter. The GFP expression levels by these promoters were various depending on cell lines tested and, in MDA-MB-231 cells, GFP activities derived from the PRC1 and RRM2 promoters were as strong as that from the cytomegalovirus (CMV) promoter. Our result showed that a vector containing the PRC1 or RRM2 promoter could be used for breast cancer specific overexpression in gene therapy.
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Neoplasias da Mama/genética , Proteínas de Ciclo Celular/genética , Marcação de Genes , Regiões Promotoras Genéticas/genética , Ribonucleosídeo Difosfato Redutase/genética , Ativação Transcricional , Neoplasias da Mama/terapia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Clonagem Molecular , Citomegalovirus , Dependovirus , Feminino , Terapia Genética , Vetores Genéticos , Proteínas de Fluorescência Verde , Humanos , Ribonucleosídeo Difosfato Redutase/metabolismoRESUMO
Gene therapy has offered highly possible promises for treatment of cancers, as many potential therapeutic genes involved in regulation of molecular processes may be introduced by gene transfer, which can arrest angiogenesis, tumor growth, invasion, metastasis, and/or can stimulate the immune response against tumors. Therefore, viral and non-viral gene delivery systems have been developed to establish an ideal delivery vector for cancer gene therapy over the past several years. Among the currently developed virus vectors, the adeno-associated virus (AAV) vector is considered as one of those that are closest to the ideal vector mainly for genetic diseases due to the following prominent features; the lack of pathogenicity and toxicity, ability to infect dividing and non-dividing cells of various tissue origins, a very low host immune response and long-term expression. Particularly, the most important attribute of AAV vectors is their safety profile in clinical trials ranging from CF to Parkinson's disease. Although adenovirus and several other oncolytic viruses have been more frequently used to develop cancer gene therapy, AAV also has many critical properties to be exploited for a cancer gene delivery vector. In this review, we will briefly summarize the basic biology of AAV and then mainly focus on recent progresses on AAV vector development and AAV-mediated therapeutic vectors for cancer gene therapy.