Journal of Biomedical Science
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Gene Therapy Strategies for Hepatocellular Carcinoma
Journal of Biomedical Science - Tập 13 - Trang 453-468 - 2006
Hepatocellular carcinoma (HCC) is one of the most frequent cancers worldwide. Effective therapy to this cancer is currently lacking, creating an urgent need for new therapeutic strategies for HCC. Gene therapy approach that relies on the transduction of cells with genetic materials, such as apoptotic genes, suicide genes, genes coding for antiangiogenic factors or immunomodulatory molecules, small interfering RNA (siRNA), or oncolytic viral vectors, may provide a promising strategy. The aforementioned strategies have been largely evaluated in the animal models with HCC or liver metastasis. Due to the diversity of vectors and therapeutic genes, being used alone or in combination, gene therapy approach may generate great beneficial effects to control the growth of tumors within the liver.
Tiềm năng điều trị của endolysins virus thực khuẩn đối với các nhiễm trùng do vi khuẩn Gram dương Dịch bởi AI
Journal of Biomedical Science - Tập 30 - Trang 1-18 - 2023
Nhiễm trùng do vi khuẩn Gram dương (G+) là gánh nặng lớn đối với cả nguồn lực y tế và y tế cộng đồng. Sự gia tăng tần suất của vi khuẩn G+ kháng đa thuốc như Staphylococcus aureus kháng methicillin (MRSA) khiến cho việc phát triển các tác nhân kháng khuẩn mới trở nên cấp thiết cho việc điều trị các nhiễm trùng do vi khuẩn G+ gây ra. Endolysins là các enzym do virus thực khuẩn (phage) mã hóa, có khả năng thủy phân cụ thể thành tế bào vi khuẩn và tiêu diệt vi khuẩn nhanh chóng. Kháng khả năng của vi khuẩn đối với endolysins là rất thấp. Do đó, endolysins được coi là các lựa chọn hứa hẹn để giải quyết vấn đề kháng thuốc ngày càng gia tăng. Trong bài tổng quan này, các endolysins được lấy từ các phage nhắm vào vi khuẩn G+ đã được phân loại dựa trên các đặc điểm cấu trúc của chúng. Cơ chế hoạt động, hiệu quả và những lợi thế của endolysins như là các ứng viên thuốc kháng khuẩn đã được tóm tắt. Hơn nữa, tiềm năng đáng kể của endolysins phage trong điều trị các nhiễm trùng do vi khuẩn G+ đã được mô tả. Ngoài ra, an toàn của endolysins, các thách thức và giải pháp khả thi cũng đã được đề cập. Mặc dù có một số hạn chế của endolysins, xu hướng phát triển cho thấy rằng các thuốc dựa trên endolysin sẽ được chấp thuận trong tương lai gần. Tổng thể, bài tổng quan này trình bày thông tin quan trọng về tiến trình hiện tại liên quan đến endolysins như là các tác nhân trị liệu tiềm năng, và nó cung cấp một hướng dẫn cho các nhà nghiên cứu vật liệu sinh học đang dành tâm huyết chống lại nhiễm trùng vi khuẩn.
#Gram-positive bacteria #endolysins #bacteriophage #antimicrobial agents #antibiotic resistance
Hepatitis B viral polymerase fusion proteins are biologically active and can interact with the hepatitis C virus core protein in vivo
Journal of Biomedical Science - Tập 8 - Trang 492-503 - 2001
Hepadnaviruses and retroviruses are evolutionarily related families because they both require a process of reverse transcription for genome replication. However, hepadnaviruses produce polymerase (pol) and core proteins separately, while retroviruses synthesize a gag-pol fusion protein that is subsequently cleaved by a virally encoded protease to release a functional polymerase. To test whether an additional sequence at the N-terminus of pol in hepatitis B virus (HBV) interferes with its function, we created two plasmids expressing core-pol fusion proteins, core144-pol and core31-pol. Secreted particles obtained from HuH-7 cells, which were cotransfected with a core-pol fusion protein-expressing plasmid and a core-expressing plasmid, showed a positive signal of HBV DNA by the endogenous polymerase assay, indicating that the core-pol fusion proteins retain DNA priming, polymerization and RNase H activities. The fusion protein was detected in the cytoplasm of transfected cells and in secreted virions by immunoprecipitation. Furthermore, we found by immunofluorescence staining that the HBV core-pol fusion protein colocalized with the hepatitis C virus (HCV) core protein in cytoplasm and in lipid droplets. Immunoprecipitation studies showed that the anti-HCV core complex contained the HBV core-pol fusion protein while the anti-HBV pol complex contained the HCV core protein, which supports the hypothesis that the HCV core protein can form a complex with the HBV core-pol fusion protein.
Mesenchymal stem cells are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction
Journal of Biomedical Science - Tập 13 - Trang 47-58 - 2005
Both cell therapy and angiogenic growth factor gene therapy have been applied to animal studies and clinical trials. Little is known about the direct comparison between cell therapy and angiogenic growth factor gene therapy. The goal of this study was to compare the effects of human bone marrow-derived mesenchymal stem cells (hMSCs) transplantation and injection of angiogenic growth factor genes in a model of acute myocardial infarction in mice. The hMSCs were obtained from adult human bone marrow and expanded in vitro. The purity and characteristics of hMSCs were identified by flow cytometry and immunophenotyping. Immediately after ligation of the left anterior descending coronary artery in male severe combined immunodeficient (SCID) mice, culture-expanded hMSCs or angiogenic growth factor genes were injected intramuscularly at the left anterior free wall. The engrafted hMSCs were positive for cardiac marker, desmin. Infarct size was significantly smaller in the hMSCs-treated group than in the angiopoietin-1 (Ang-1) or vascular endothelial growth factor (VEGF)-treated group at day 28 after infarction. hMSCs transplantation was better in decreasing left ventricular end-diastolic dimension and increasing fractional shortening than Ang1 or VEGF gene therapy. Capillary density was markedly increased after hMSCs transplantation than Ang1 and VEGF gene therapy. In conclusion, intramyocardial transplantation of hMSCs improves cardiac function after acute myocardial infarction through enhancement of angiogenesis and myogenesis in the ischemic myocardium. hMSCs are superior to angiogenic growth factor genes for improving myocardial performance in the mouse model of acute myocardial infarction. Transplantation of MSCs may become the future therapy for acute myocardial infarction for myocardial regeneration.
Bacteriophages and antibiotic interactions in clinical practice: what we have learned so far
Journal of Biomedical Science - Tập 29 - Trang 1-17 - 2022
Bacteriophages (phages) may be used as an alternative to antibiotic therapy for combating infections caused by multidrug-resistant bacteria. In the last decades, there have been studies concerning the use of phages and antibiotics separately or in combination both in animal models as well as in humans. The phenomenon of phage–antibiotic synergy, in which antibiotics may induce the production of phages by bacterial hosts has been observed. The potential mechanisms of phage and antibiotic synergy was presented in this paper. Studies of a biofilm model showed that a combination of phages with antibiotics may increase removal of bacteria and sequential treatment, consisting of phage administration followed by an antibiotic, was most effective in eliminating biofilms. In vivo studies predominantly show the phenomenon of phage and antibiotic synergy. A few studies also describe antagonism or indifference between phages and antibiotics. Recent papers regarding the application of phages and antibiotics in patients with severe bacterial infections show the effectiveness of simultaneous treatment with both antimicrobials on the clinical outcome.
Effects of colonization-associated gene yqiC on global transcriptome, cellular respiration, and oxidative stress in Salmonella TyphimuriumAbstract
Background
yqiC is required for colonizing the Salmonella enterica serovar Typhimurium (S . Typhimurium) in human cells; however, how yqiC regulates nontyphoidal Salmonella (NTS) genes to influence bacteria–host interactions remains unclear.
Methods
The global transcriptomes of S . Typhimurium yqiC -deleted mutant (ΔyqiC ) and its wild-type strain SL1344 after 2 h of in vitro infection with Caco-2 cells were obtained through RNA sequencing to conduct comparisons and identify major yqiC -regulated genes, particularly those involved in Salmonella pathogenicity islands (SPIs), ubiquinone and menaquinone biosynthesis, electron transportation chains (ETCs), and carbohydrate/energy metabolism. A Seahorse XFp Analyzer and assays of NADH/NAD+ and H2 O2 were used to compare oxygen consumption and extracellular acidification, glycolysis parameters, adenosine triphosphate (ATP) generation, NADH/NAD+ ratios, and H2 O2 production between ΔyqiC and SL1344.
Results
After S . Typhimurium interacts with Caco-2 cells, yqiC represses gene upregulation in aspartate carbamoyl transferase, type 1 fimbriae, and iron–sulfur assembly, and it is required for expressing ilvB operon, flagellin, tdc ABCD, and dms AB. Furthermore, yqiC is required for expressing mainly SPI-1 genes and specific SPI-4, SPI-5, and SPI-6 genes; however, it diversely regulates SPI-2 and SPI-3 gene expression. yqiC significantly contributes to menD expression in menaquinone biosynthesis. A Kyoto Encyclopedia of Genes and Genomes analysis revealed the extensive association of yqiC with carbohydrate and energy metabolism. yqiC contributes to ATP generation, and the analyzer results demonstrate that yqiC is required for maintaining cellular respiration and metabolic potential under energy stress and for achieving glycolysis, glycolytic capacity, and glycolytic reserve. yqiC is also required for expressing ndh , cydA , nuoE , and sdhB but suppresses cyoC upregulation in the ETC of aerobically and anaerobically grown S . Typhimurium; priming with Caco-2 cells caused a reversed regulation of yiqC toward upregulation in these ETC complex genes. Furthermore, yqiC is required for maintaining NADH/NAD+ redox status and H2 O2 production.
Conclusions
Specific unreported genes that were considerably regulated by the colonization-associated gene yqiC in NTS were identified, and the key role and tentative mechanisms of yqiC in the extensive modulation of virulence factors, SPIs, ubiquinone and menaquinone biosynthesis, ETCs, glycolysis, and oxidative stress were discovered.
Journal of Biomedical Science -
SRF: a seriously responsible factor in cardiac development and disease
Journal of Biomedical Science - Tập 29 - Trang 1-21 - 2022
The molecular mechanisms that regulate embryogenesis and cardiac development are calibrated by multiple signal transduction pathways within or between different cell lineages via autocrine or paracrine mechanisms of action. The heart is the first functional organ to form during development, which highlights the importance of this organ in later stages of growth. Knowledge of the regulatory mechanisms underlying cardiac development and adult cardiac homeostasis paves the way for discovering therapeutic possibilities for cardiac disease treatment. Serum response factor (SRF) is a major transcription factor that controls both embryonic and adult cardiac development. SRF expression is needed through the duration of development, from the first mesodermal cell in a developing embryo to the last cell damaged by infarction in the myocardium. Precise regulation of SRF expression is critical for mesoderm formation and cardiac crescent formation in the embryo, and altered SRF levels lead to cardiomyopathies in the adult heart, suggesting the vital role played by SRF in cardiac development and disease. This review provides a detailed overview of SRF and its partners in their various functions and discusses the future scope and possible therapeutic potential of SRF in the cardiovascular system.
Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells
Journal of Biomedical Science - Tập 13 - Trang 525-533 - 2006
Arsenic is an established human carcinogen. The role of aquaglyroporins (AQPs) in arsenic disposition was recently identified. In order to examine whether organic anion transporting polypeptide-C (OATP-C) also plays a role in arsenic transport, OATP-C cDNA was transfected into cells of a human embryonic kidney cell line (HEK-293). Transfection increased uptake of the model OATP-C substrate, estradiol-17β-D-glucuronide, by 10-fold. In addition, we measured uptake and cytotoxicity of arsenate, arsenite, monomethylarsonate(MMAV), and dimethylarsinate (DMAV). Transfection of OATP-C increased uptake and cytotoxicity of arsenate and arsenite, but not of MMAV or DMAV. Rifampin and taurocholic acid (a substrate of OATP-C) reversed the increased toxicity of arsenate and arsenite seen in OATP-C-transfected cells. The increase in uptake of inorganic arsenic was not as great as that of estradiol-17β-D-glucuronide. Our results suggest that OATP-C can transport inorganic arsenic in a (GSH)-dependent manner. However, this may not be the major pathway for arsenic transport.
Drosophila king tubby (ktub) mediates light-induced rhodopsin endocytosis and retinal degeneration
Journal of Biomedical Science - Tập 19 - Trang 1-12 - 2012
The tubby (tub) and tubby-like protein (tulp) genes encode a small family of proteins found in many organisms. Previous studies have shown that TUB and TULP genes in mammalian involve in obesity, neural development, and retinal degeneration. The purpose of this study was to investigate the role of Drosophila king tubby (ktub) in rhodopsin 1 (Rh1) endocytosis and retinal degeneration upon light stimulation. Drosophila ktub mutants were generated using imprecise excision. Wild type and mutant flies were raised in dark or constant light conditions. After a period of light stimulation, retinas were dissected, fixed and stained with anti-Rh1 antibody to reveal Rh1 endocytosis. Confocal and transmission electron microscope were used to examine the retinal degeneration. Immunocytochemical analysis shows that Ktub is expressed in the rhabdomere domain under dark conditions. When flies receive light stimulation, the Ktub translocates from the rhabdomere to the cytoplasm and the nucleus of the photoreceptor cells. Wild type photoreceptors form Rh1-immunopositive large vesicles (RLVs) shortly after light stimulation. In light-induced ktub mutants, the majority of Rh1 remains at the rhabdomere, and only a few RLVs appear in the cytoplasm of photoreceptor cells. Mutation of norpA allele causes massive Rh1 endocytosis in light stimulation. In ktub and norpA double mutants, however, Rh1 endocytosis is blocked under light stimulation. This study also shows that ktub and norpA double mutants rescue the light-induced norpA retinal degeneration. Deletion constructs further demonstrate that the Tubby domain of the Ktub protein participates in an important role in Rh1 endocytosis. The results in this study delimit the novel function of Ktub in Rh1 endocytosis and retinal degeneration.
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