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Background: Therapeutic gene transfer is currently being evaluated as a potential therapy for inflammatory bowel disease. This study investigates the safety and therapeutic benefit of a locally administered lentiviral vector encoding murine interleukin-10 in altering the onset and relapse of dextran sodium sulfate induced murine colitis.
Methods: Lentiviral vectors encoding the reporter genes firefly-luciferase and murine interleukin-10 were administered by intrarectal instillation, either once or twice following an ethanol enema to facilitate mucosal uptake, on Days 3 and 20 in Balb/c mice with acute and relapsing colitis induced with dextran sulfate sodium (DSS). DSS colitis was characterized using clinical disease activity, macroscopic, and microscopic scores. Bioluminescence optical imaging analysis was employed to examine mucosal lentiviral vector uptake and transgene expression. Levels of tumor necrosis factor-α and interleukin-6 in homogenates of rectal tissue were measured by ELISA. Biodistribution of the lentiviral vector to other organs was evaluated by real time quantitative PCR.
Results: Mucosal delivery of lentiviral vector resulted in significant transduction of colorectal mucosa, as shown by bioluminescence imaging analysis. Lentiviral vector-mediated local expression of interleukin-10 resulted in significantly increased levels of this cytokine, as well as reduced levels of tumor necrosis factor-α and interleukin-6, and significantly reduced the clinical disease activity, macroscopic, and microscopic scores of DSS colitis. Systemic biodistribution of locally instilled lentiviral vector to other organs was not detected.
Conclusions: Topically-delivered lentiviral vectors encoding interleukin-10 safely penetrated local mucosal tissue and had therapeutic benefit in this DSS model of murine colitis.
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http://dx.doi.org/10.1186/1471-230X-14-68 | DOI Listing |
Exp Cell Res
December 2024
Department of Anesthesiology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu Province, 215006, China; Institute of Anesthesiology, Soochow University, Suzhou City, Jiangsu Province, 215006, China. Electronic address:
Background And Objective: Neuropathic pain, a debilitating condition stemming from nervous system injuries, has profound impacts on quality of life. The medial prefrontal cortex (mPFC) plays a crucial role in the modulation of pain perception and emotional response. This study explores the involvement of Slingshot Homolog 1 (SSH1) protein in neuropathic pain and related emotional and cognitive dysfunctions in a mouse model of spared nerve injury (SNI).
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Department of Stomatology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuhan 430071, China. Electronic address:
Purpose: This study investigated TMED2 expression in oral squamous cell carcinoma (OSCC) and its effects on SCC9 cell behaviors, including proliferation, migration, invasion, and autophagy, to support OSCC diagnosis and treatment.
Methods: TMED2 expression was analyzed in TCGA and GEO databases, and protein levels in OSCC tissues were examined via HE staining and tissue microarrays. SCC9 cells, with high TMED2 expression, were used to assess TMED2's effects on cell proliferation, invasion, and cell cycle.
Int J Mol Sci
December 2024
Amsterdam UMC location Vrije Universiteit Amsterdam, Medical Oncology, De Boelelaan 1117, 1081 HV Amsterdam, The Netherlands.
The core spliceosome Sm proteins are gaining attention as potential targets for cancer treatment. Here, we evaluate this, with focus on SmD2. A pan-cancer analysis including 26 solid tumor types revealed that the SmD2-encoding gene was overexpressed in almost all cancers.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Anatomy, School of Biomedical Sciences, University of Otago, Dunedin 9054, New Zealand.
Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder. However, the core biology of the disorder that leads to the hypofunctioning of the cerebral dopaminergic network requires further elucidation. We investigated midbrain synaptic changes in male rats exposed to repeated hypoxia during the equivalent of extreme prematurity, which is a new animal model of the hyperactive/impulsive presentation of ADHD.
View Article and Find Full Text PDFCells
November 2024
Great Ormond Street Institute of Child Health, University College London, London WC1E 1EH, UK.
Recently approved adeno-associated viral (AAV) vectors for liver monogenic diseases haemophilia A and B are exemplifying the success of liver-directed viral gene therapy. In parallel, additional gene therapy strategies are rapidly emerging to overcome some inherent AAV limitations, such as the non-persistence of the episomal transgene in the rapidly growing liver and immune response. Viral integrating vectors such as in vivo lentiviral gene therapy and non-viral vectors such as lipid nanoparticles encapsulating mRNA (LNP-mRNA) are rapidly being developed, currently at the preclinical and clinical stages, respectively.
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