Adenoviral vectors, both oncolytic viruses and gene delivery vectors, are among the earliest approved and commercialised vectors for gene therapy. Adenoviruses have high cytotoxicity and immunogenicity. Therefore, lentiviruses or adeno-associated viruses as viral vectors and herpes simplex virus as an oncolytic virus have recently drawn attention.
View Article and Find Full Text PDFγ-aminobutyric acid (GABA) is a major inhibitory neurotransmitter and its concentrations in the brain could be associated with EtOH-induced impairment of motor coordination. GABA is synthesized by two isoforms of glutamate decarboxylase (GAD): GAD65 and GAD67. Mice deficient in GAD65 (GAD65-KO) can grow up to adulthood, and show that GABA concentration in their adult brains was 50-75% that of wild-type C57BL/6 mice (WT).
View Article and Find Full Text PDFIt has previously been found that turnip mosaic virus (TuMV) greatly suppresses anthocyanin accumulation (AA) in Brassica rapa leaves, and that such leaves become infected whilst anthocyanin-enriched leaves on the same plants are rarely infected. To clarify whether AA is a defense against TuMV, in this study we examined tissue-level patterns of spontaneous AA in relation to the cellular localization of a TuMV strain that expresses a yellow fluorescent protein. We found that TuMV infection was significantly blocked by AA, suggesting that it functions as a chemical barrier against TuMV.
View Article and Find Full Text PDFAn increase in nicotinamide adenine dinucleotide (NAD) levels alleviates age-related disease progression and promotes healthy life expectancy. Several studies have demonstrated that NAD levels can be efficiently replenished via nicotinamide mononucleotide (NMN) intake; additionally, the safety of its oral ingestion has been confirmed in recent clinical trials. However, the efficacy and safety of intravenous NMN administration in humans remain unclear.
View Article and Find Full Text PDFGene therapy using vectors has attracted attention in recent years for the treatment of cancers caused by gene mutations. Besides, new treatments are imperative for lung cancer, including non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM), due to its high mortality. We developed a minimally invasive and orally inhalable tumor suppressor gene drug (SFD-p16 and SFD-p53) with non-viral vectors for lung cancer treatment by combining tumor suppressor genes with an inhalant powder that can deliver active ingredients directly to the lung.
View Article and Find Full Text PDFCancer stem cells (CSCs) are major contributors to the malignant transformation of cells because of their capacity for self-renewal. Aldehyde dehydrogenase1A1 (ALDH1A1) and CD133 are promising candidate of CSC markers in non-small cell lung cancer (NSCLC). Furthermore, TP53 is frequently mutated in lung cancer, and the loss of its function is associated with malignant characteristics.
View Article and Find Full Text PDFCrosses of parents that differ in their DNA methylation states leads to progressive demethylation in the F hybrids. In plant breeding research, hybrid vigor in F hybrids is known to be a very important phenomenon. Hybrid vigor, or heterosis, refers to the fact that F hybrids from crosses with a certain combination of parents have traits that are superior to those of the parents.
View Article and Find Full Text PDFBackground: The clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR-Cas9) is thought to have promising clinical potential. However, the off-target effects of Cas9 are a major concern for its application. Therefore, we hypothesized that the adverse effects of off-target gene editing might be minimized if the human codon-optimized Streptococcus pyogenes Cas9 (hCas9) could be specifically expressed in cancer cells.
View Article and Find Full Text PDFBackground/aim: CD133 is a promising candidate marker for cancer stem cells. However, clinical studies on CD133 expression in human lung adenocarcinoma have not yet been conducted. We hypothesized that CD133 expression in lung adenocarcinoma is a poor prognostic factor.
View Article and Find Full Text PDF: To investigate predictors of acute kidney injury (AKI) following open aortic repair (OAR) requiring suprarenal clamping. : The study included 833 nonhemodialysis patients who had undergone elective OAR (with suprarenal clamping, n=73; with infrarenal clamping, n=760). We evaluated AKI as defined by the criteria of the Kidney Disease Improving Global Outcomes (KDIGO) and compared in-hospital outcomes between the two groups.
View Article and Find Full Text PDFObjectives: Outcomes of planned and unplanned (rescue) double arterial cannulation (DAC) in surgery for acute type A aortic dissection were investigated retrospectively.
Methods: The study involved 805 patients who were divided into 4 groups according to the cannulation strategy: single cannulation of the femoral artery (n = 338), axillary artery (n = 256), left ventricular apex (n = 52) or ascending aorta (n = 5) (total, n = 57), and DAC (n = 154). Patients who underwent DAC were divided between planned (n = 132) and rescue (n = 22) usage.
We carried out structure-activity relationship study on anti-cancer effects of naftopidil (1) and its metabolites, resulted in identification of 1-(4-hydroxy-2-methoxyphenyl)piperazin-1-yl)-3-(naphthalen-1-yloxy) propan-2-ol (2, HUHS190), a major human metabolite of 1, which exhibited the most selective toxicities between against normal and cancer cells (Table 1). 2 was more hydrophilic compared to 1, was enough to be prepared in high concentration solution of more than 100 μM in saline for an intravesical instillation drug. Moreover, serum concentration of 2 was comparable to that of 1, an oral preparation drug, after oral administration at 32 mg/kg (Fig.
View Article and Find Full Text PDFBackground: The safety of intraoperative administration of hydroxyethyl starch (HES) has been debated. We hypothesized that intraoperative use of HES is associated with postoperative acute kidney injury (AKI) following cardiopulmonary bypass (CPB).
Materials And Methods: Patients who underwent cardiothoracic surgery using CPB between 2007 and 2014 were retrospectively reviewed.
Background: De novo DNA methylation triggered by short interfering RNAs is called RNA-directed DNA methylation (RdDM). Transcriptional gene silencing (TGS) through RdDM can be induced using a viral vector. We have previously induced RdDM on the 35S promoter in the green fluorescent protein (GFP)-expressing Nicotiana benthamiana line 16c using the cucumber mosaic virus vector.
View Article and Find Full Text PDFBackground/aim: Currently, treatment of non-muscle invasive bladder cancer causes significant deterioration in a patient's quality of life (QOL). Therefore, development of novel therapeutic options without the deterioration of QOL is very important. In this study, we assessed the anti-tumor effect of lentivirus-mediated gene transfection of tumor-suppressor genes in human bladder cancer cells.
View Article and Find Full Text PDFAnticancer Res
February 2018
Aim: Naftopidil is used to treat benign prostate hyperplasia. Moreover, previous studies have shown that naftopidil reduced viability of many types of cancer cells. Therefore, we investigated the antitumor mechanism of naftopidil in this study.
View Article and Find Full Text PDFA transposition of a heat-activated retrotransposon named ONSEN required compromise of a small RNA-mediated epigenetic regulation that includes RNA-directed DNA methylation (RdDM) machinery after heat treatment. In the current study, we analyzed the transcriptional and transpositional activation of ONSEN to better understand the underlying molecular mechanism involved in the maintenance and/or induction of transposon activation in plant tissue culture. We found the transposition of heat-primed ONSEN during tissue culture independently of RdDM mutation.
View Article and Find Full Text PDFNatural accessions are used for studying intraspecies genetic variation in the model plant Arabidopsis thaliana in order to address fundamental questions of evolution. Transposable elements are responsible for a wide range of mutations and play significant roles in shaping a genome over evolutionary time. In the present study, we aimed to characterize ONSEN, a heat-activated long terminal repeat (LTR) retrotransposon, in natural A.
View Article and Find Full Text PDFTransposable elements (TEs), or transposons, play an important role in adaptation. TE insertion can affect host gene function and provides a mechanism for rapid increases in genetic diversity, particularly because many TEs respond to environmental stress. In the current study, we show that the transposition of a heat-activated retrotransposon, ONSEN, generated a mutation in an abscisic acid (ABA) responsive gene, resulting in an ABA-insensitive phenotype in Arabidopsis, suggesting stress tolerance.
View Article and Find Full Text PDFChondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix (ECM) in the brain. In adult mammals, CSPGs form the specialized ECM structure perineuronal nets (PNNs) that surround somata and dendrites of certain types of neurons. PNNs restrict synaptic plasticity and regulate the closure of critical periods.
View Article and Find Full Text PDFTransposable elements (TEs) are key elements that facilitate genome evolution of the host organism. A number of studies have assessed the functions of TEs, which change gene expression in the host genome. Activation of TEs is controlled by epigenetic modifications such as DNA methylation and histone modifications.
View Article and Find Full Text PDFAdverse experiences in early life can affect the formation of neuronal circuits during postnatal development and exert long-lasting influences on neural function. Many studies have shown that daily repeated maternal separation (RMS), an animal model of early life stress, can modulate the hypothalamic-pituitary-adrenal axis (HPA-axis) and can affect subsequent brain function and emotional behavior during adulthood. However, the molecular basis of the long-lasting effects of early life stress on brain function has not been completely elucidated.
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