Current gene therapy最新文献

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.

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.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the most prevalent malignancyof the pancreas, and the incidence of this disease is approximately equivalent to the mortality rate.Immunotherapy has made a remarkable breakthrough in numerous cancers, while its efficacy inPDAC remains limited due to the immunosuppressive microenvironment. Immunotherapy efficacy ishighly correlated with the abundance of immune cells, particularly cytotoxic T cells. Therefore, molecular classifier is needed to identify relatively hot tumors that may benefit from immunotherapy

Method: In this study, we carried out a transcriptome analysis of 145 pancreatic tumors to define the underlying immune regulatory mechanism driving the PDAC immunosuppressive microenvironment. Theimmune subtype was identified by consensus clustering, and the underlying PDAC immune activationmechanism was thoroughly examined using single sample gene set enrichment analysis (ssGSEA). Areaunder the curve (AUC) of the receiver operating characteristic (ROC) curve was used to assess the accuracy of the molecular classifier in differentiating immunological subgroups of PDAC.5

Result: The protein level of molecular classifier was verified by immunohistochemistry in humanPDAC tissue. Immune-hot tumors displayed higher levels of immune cell infiltration and immunecheckpoint, in line with enriched immune escape pathways. Hematopoietic cell signal transducer(HCST), a molecular classifier used to differentiate immunological subtypes of PDAC, has shown asubstantial link with the expression levels of cytotoxic markers, such as CD8A and CD8B. At the single cell level, we found that HCST was predominantly expressed in CD8T cells. By immunohistochemistry and survival analysis, we further demonstrated the prognostic value of HCST in PDAC.

Conclusion: We identified HCST as a molecular classifier to distinguish PDAC immune subtypes,which may be useful for early diagnosis and targeted therapy of PDAC.

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.

Leukemia is a type of cancer that affects white blood cells. In this disease, immature blood cells undergo genetic mutations, leading to excessive replication and reduced cell death compared to healthy cells. In cancer, there may be the activation of oncogenes and the deactivation of tumor suppressor genes that control certain cellular functions. Despite the undeniable contribution to the patient's recovery, conventional cancer treatments may have some not-so-beneficial effects. In this case, gene therapy appears as an alternative to classical treatments. Gene therapy delivers genetic material to cells to replace or modify dysfunctional genes, a safe method for neoplasms. One of the types of nucleic acids explored in gene therapy is microRNA (miRNA), a group of endogenous, non-proteincoding, small single-stranded RNA molecules involved in the regulation of gene expression, cell division, differentiation, angiogenesis, migration, apoptosis, and carcinogenesis. This review aims to bring together the most recent advances found in the literature on cancer gene therapy based on microRNAs in the oncological context, focusing on leukemia.