Current gene therapy最新文献

Background: The development of novel biomarkers is crucial for the treatment of HCC. In this study, we investigated a new molecular therapeutic target for HCC. Fidgetin-like 1 (FIGNL1) has been reported to play a vital role in lung adenocarcinoma. However, the potential function of FIGNL1 in HCC is still unknown.

Objective: This study aims to investigate the key regulatory mechanisms of FIGNL1 in the formation of HCC.

Methods: The regulatory effect of FIGNL1 on HCC was studied by lentivirus infection. In vitro, the effects of FIGNL1 on the proliferation, migration and apoptosis of cells were investigated by CCK8, colony formation assay, transwell and flow cytometry. Meanwhile, the regulation of FIGNL1 on HCC formation in vivo was studied by subcutaneous transplanted tumors. In addition, using transcriptome sequencing technology, we further explored the specific molecular mechanism of FIGNL1 regulating the formation of HCC.

Results: Functionally, we demonstrated that FIGNL1 knockdown significantly inhibited HCC cell proliferation, migration and promoted cell apoptosis in vitro. Similarly, the knockdown of FIGNL1 meaningfully weakened hepatocarcinogenesis in nude mice. Transcriptome sequencing revealed that FIGNL1 affected the expression of genes involved in extracellular matrix-receptor (ECM-receptor) interaction pathway, such as hyaluronan mediated motility receptor (HMMR). Further validation found that overexpression of HMMR based on knockdown FIGNL1 can rescue the expression abundance of related genes involved in the ECM-receptor interaction pathway.

Conclusion: Our study revealed that FIGNL1 could modulate the ECM-receptor interaction pathway through the regulation of HMMR, thus regulating the formation of HCC.

Gene therapy for hemophilia has advanced tremendously after thirty years of continual study and development. Advancements in medical science have facilitated attaining normal levels of Factor VIII (FVIII) or Factor IX (FIX) in individuals with haemophilia, thereby offering the potential for their complete recovery. Despite the notable advancements in various countries, there is significant scope for further enhancement in haemophilia gene therapy. Adeno-associated virus (AAV) currently serves as the primary vehicle for gene therapy in clinical trials targeting haemophilia. Subsequent investigations will prioritize enhancing viral capsid structures, transgene compositions, and promoters to achieve heightened transduction efficacy, diminished immunogenicity, and more predictable therapeutic results. The present study indicates that whereas animal models have transduction efficiency that is over 100% high, human hepatocytes are unable to express clotting factors and transduction efficiency to comparable levels. According to the current study, achieving high transduction efficiency and high levels of clotting factor expression in human hepatocytes is still insufficient. It is also crucial to reduce the risk of cellular stress caused by protein overload. Despite encountering various hurdles, the field of haemophilia gene therapy holds promise for the future. As technology continues to advance and mature, it is anticipated that a personalized therapeutic approach will be developed to cure haemophilia effectively.

Background: Segmentation of medical images plays a key role in the correct identification and management of different diseases. In this study, we present a new segmentation method that meets the difficulties posed by sophisticated organ shapes in computed tomography (CT) images, particularly targeting lung, breast, and gastric cancers.

Methods: Our suggested methods, Resio-Inception U-Net and Deep Cluster Recognition (RIUDCR), use a Residual Inception Architecture, which combines the power of residual connections and inception blocks to achieve cutting-edge segmentation performance while reducing the risk of overfitting.

Results: We present mathematical equations and functions that describe the design, including the encoding and decoding steps within the UC-Net system. Furthermore, we provide strong testing results that show the effectiveness of our method. Through thorough testing on varied datasets, our method regularly beats current techniques, achieving amazing precision and stability in organ task segmentation. These results show the promise of our residual inception architecture in better medical picture analysis.

Conclusion: In summary, our research not only shows a state-of-the-art segment methodology but also reinforces its usefulness through thorough testing. The inclusion of residual inception architecture in medical picture segmentation offers good possibilities for improving the identification and management of disease planning.

As one of the main characteristics of neoplasia, metabolic reprogramming provides nutrition and energy to enhance cell proliferation and maintain environment homeostasis. Glycolysis is one of the most important components of cancer metabolism and the Warburg effect contributes to the competitive advantages of cancer cells in the threatened microenvironment. Studies show strong links between N⁶-methyladenosine (m⁶A) modification and metabolic recombination of cancer cells. As the most abundant modification in eukaryotic RNA, m⁶A methylation plays important roles in regulating RNA processing, including splicing, stability, transportation, translation and degradation. The aberration of m⁶A modification can be observed in a variety of diseases such as diabetes, neurological diseases and cancers. This review describes the mechanisms of m⁶A on cancer glycolysis and their applications in cancer therapy and prognosis evaluation, aiming to emphasize the importance of targeting m⁶A in modulating cancer metabolism.

Aim: Duchenne Muscular Dystrophy (DMD) results in a deficiency of dystrophin expression in patient muscle fibers, leading to progressive muscle degeneration. Treatment of DMD has undertaken current transformation with the advancement of novel gene therapy and molecular biology techniques, which are secure, well-tolerated, and effective therapeutic approaches.

Introduction: DMD gene therapies have mainly focused on young DMD patients as in vivo animal model trials have been performed in 0-1-month DMD mice. However, it has not yet been answered how micro-dystrophin encoding lentiviral treatment affects Dystrophin expression and DMD symptoms in 10-month mdx mice.

Methods: We planned to integrate the micro-Dystrophin gene sequence into the muscle cells by viral transfer, using micro-Dystrophin-encoding lentivirus to reduce the dystrophic pathology in late-stage dmd mice. The histopathological and physiological-functional regeneration activities of the lentiviralmicro- Dystrophin gene therapy methods were compared, along with changes in temporal Dystrophin expression and their functionality, toxicity, and gene expression level.

Results: Here, we showed that the micro-dystrophin transgene transfers intramuscularly and intraperitoneally in late-stage dmd-mdx-4cv mice restored dystrophin expression in the skeletal and cardiac muscle (p <0.001). Furthermore, motor performance analysis, including hanging and tracking tests, improved statistically significantly after the treatment (p <0.05).

Conclusion: Consequently, this study suggests that patients in the late stages of muscular dystrophy can benefit from lentiviral micro-dystrophin gene therapies to present an improvement in dystrophic muscle pathology.