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Objective: To study the therapeutic effects of recombinant adeno-associated virus (rAAV) expressing fusion peptide NT4p53(C22)Ant against transplanted liver cancer in ICR mice.
Methods: NT4p53(C22)Ant was constructed, subcloned into recombinant AAV vector, and amplified in 293 packaging cells. The efficacy of rAAV-NT4p53(C22)Ant on tumors derived from H22 cells inoculated subcutaneously in IRC mice was evaluated according to the tumor weight, inhibition rate, survival time of the mice and the histological findings.
Results: A single dose of rAAV-NT4p53(C22)Ant of 100 microl (2 x 10(11) pfu/ml) injected into the transplanted H22 tumors in the ICR mice resulted in tumor disappearance in 7 (totally 12) mice, and death occurred in only 1 mouse. The injection also resulted in decreased tumor weight and prolonged survival of the mice (for over 70 days). All the 7 mice with only rAAV injection or no treatment all died, with a mean survival of about 30 days. The tumor inhibition rate exceeded 90% in mice with rAAV-NT4p53(C22)Ant injection, significantly higher than that of mice without the injection. The histological examination revealed significantly decreased tumor cells in mice with rAAV-NT4p53(C22)Ant injection as compared with those without such treatment.
Conclusion: rAAV-NT4p53(C22)Ant can induce apoptosis of the H22 tumor cells transplanted in IRC mice to inhibit the tumor growth and prolong the survival of the mice.
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JCI Insight
September 2025
Edinburgh Medical School: Biomedical Sciences & Euan MacDonald Centre for M, University of Edinburgh, Edinburgh, United Kingdom.
Spinal muscular atrophy (SMA) is a neuromuscular disease caused by low levels of SMN protein. Several therapeutic approaches boosting SMN are approved for human patients, delivering remarkable improvements in lifespan and symptoms. However, emerging phenotypes, including neurodevelopmental comorbidities, are being reported in some treated SMA patients, indicative of alterations in brain development.
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September 2025
Department of Pharmacology, University of Michigan, Ann Arbor, United States of America.
Cardiac hypertrophy is a common adaptation to cardiovascular stress and often a prelude to heart failure. We examined how S-palmitoylation of the small GTPase, Ras-related C3 botulinum toxin substrate 1 (Rac1), impacts cardiomyocyte stress signaling. Mutation of the cysteine-178 palmitoylation site impaired activation of Rac1 when overexpressed in cardiomyocytes.
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September 2025
Diabetes & Metabolism Research Center, University of Utah, Salt Lake City, United States of America.
Impaired muscle regrowth in aging is underpinned by reduced pro-inflammatory macrophage function and subsequently impaired muscle cellular remodeling. Macrophage phenotype is metabolically controlled through TCA intermediate accumulation and activation of HIF1A. We hypothesized that transient hypoxia following disuse in old mice would enhance macrophage metabolic inflammatory function thereby improving muscle cellular remodeling and recovery.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
School of Medicine, Chongqing University, Chongqing 400044, China.
Engineering functional exosomes represents a cutting-edge approach in biomedicine, holding the promise to transform targeted therapy. However, challenges such as achieving consistent modification and scalability have limited their wider adoption. Herein, we introduce a universal and effective strategy for engineering multifunctional exosomes through cell fusion.
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September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drugs Research, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug De
Proliferative retinopathy is a leading cause of irreversible blindness in humans; however, the molecular mechanisms behind the immune cell-mediated retinal angiogenesis remain poorly elucidated. Here, using single-cell RNA sequencing in an oxygen-induced retinopathy (OIR) model, we identified an enrichment of sorting nexin (SNX)-related pathways, with SNX3, a member of the SNX family that is involved in endosomal sorting and trafficking, being significantly upregulated in the myeloid cell subpopulations of OIR retinas. Immunostaining showed that SNX3 expression is markedly increased in the retinal microglia/macrophages of mice with OIR, which is mainly located within and around the neovascular tufts.
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