Prostate cancer is one of the predominant cancers affecting men and has been widely reported. In the past, various therapies and drugs have been proposed to treat prostate cancer. Among these treatments, gene therapy has been considered to be an optimal and widely applicable treatment. Furthermore, due to the increased specificity of gene sequence complementation, the targeted delivery of complementary gene sequences may represent a useful treatment in certain instances. Various gene therapies, including tumor-suppressor gene therapy, suicide gene therapy, immunomodulation gene therapy and anti-oncogene therapies, have been established to treat a wide range of diseases, such as cardiac disease, cystic fibrosis, HIV/AIDS, diabetes, hemophilia, and cancers. To this end, several gene therapy clinical trials at various phases are underway. This overview describes the developments and progress in gene therapy, with a special focus being placed on prostate cancer.
As human life expectancy increases substantially and aging is the primary risk factor for most chronic diseases, there is an urgent need for advancing the development of post-genomic era biomarkers that can be used for disease prediction and early detection (DPED). Mosaic loss of Y chromosome (LOY) is the state of nullisomy Y in sub-groups of somatic cells acquired from different post-zygotic development stages and onwards throughout the lifespan. Multiple large-cohort based epidemiology studies have found that LOY in blood cells is a significant risk factor for future mortality and various diseases in males. Many features intrinsic to LOY analysis may be leveraged to enhance its use as a non-invasive, sensitive, reliable, high throughput-biomarker for DPED. Here, we review the emerging literatures in LOY studies and highlight ten strengths for using LOY as a novel biomarker for genomics-driven DPED diagnostics. Meanwhile, the current limitations in this area are also discussed. We conclude by identifying some important knowledge gaps regarding the consequences of malsegregation of the Y chromosome and propose further steps that are required before clinical implementation of LOY. Taken together, we think that LOY has substantial potential as a biomarker for DPED, despite some hurdles that still need to be addressed before its integration into healthcare becomes acceptable.
Heart failure is a major killer worldwide. Atrioventricular conduction block is common in heart failure; it is associated with worse outcomes and can lead to syncope and bradycardic death. We examine the effect of heart failure on anatomical and ion channel remodelling in the rabbit atrioventricular junction (AVJ). Heart failure was induced in New Zealand rabbits by disruption of the aortic valve and banding of the abdominal aorta resulting in volume and pressure overload. Laser micro-dissection and real-time polymerase chain reaction (RT-PCR) were employed to investigate the effects of heart failure on ion channel remodelling in four regions of the rabbit AVJ and in septal tissues. Investigation of the AVJ anatomy was performed using micro-computed tomography (micro-CT). Heart failure animals developed first degree heart block. Heart failure caused ventricular myocardial volume increase with a 35% elongation of the AVJ. There was downregulation of HCN1 and Cx43 mRNA transcripts across all regions and downregulation of Cav1.3 in the transitional tissue. Cx40 mRNA was significantly downregulated in the atrial septum and AVJ tissues but not in the ventricular septum. mRNA abundance for ANP, CLCN2 and Navβ1 was increased with heart failure; Nav1.1 was increased in the inferior nodal extension/compact node area. Heart failure in the rabbit leads to prolongation of the PR interval and this is accompanied by downregulation of HCN1, Cav1.3, Cx40 and Cx43 mRNAs and anatomical enlargement of the entire heart and AVJ.
Hybrid sedimentary rocks (HSR) represent a significant reservoir type in fine-grained sediments. However, the classification and understanding of HSR reservoirs, including their storage mechanisms and identification of optimal "sweet spots," have been limited due to the lack of clarity regarding the multiple sources of components and their mixing processes. This study focuses on the Lucaogou formation of Jimusaer Sag and aims to highlight the reservoir classification principles, controlling factors, and evolutionary patterns associated with the components of HSR, beginning with examining the microscopic pore structure. The analysis of the microscopic pore structure characteristics reveals the presence of five distinct reservoir types within the HSR. The quality of these reservoirs is governed by various factors, including the composition and support mode of particles, diagenesis, provenance, and sedimentary microfacies. In regions near a provenance with strong hydrodynamic conditions, the HSR predominantly exhibits type I and type II reservoirs, characterized by numerous coarse-grained components and a granular-support mode. As the distance from the provenance increases, transitioning into medium hydrodynamic conditions, the HSR shifts to an interbedded-support mode, primarily developing type III reservoirs. In areas far from the provenance with weak hydrodynamic conditions, HSR reservoir types primarily consist of type IV and type V. Additionally, diagenetic effects such as compaction and calcite cementation further deteriorate intergranular and dissolution pores, consequently diminishing reservoir quality. Notably, during the mixing deposition processes of sand and dolomite, the developmental mode of HSR shifts from type I to type II and type III. Likewise, in the mixing deposition of mud and sand, the HSR transitions from type II to type III and type IV. Similarly, the mixing deposition of dolomite and mud leads to a change in the developmental mode of HSR from type III to type IV and type V. Moreover, this study effectively predicts the occurrence of "sweet spots" using reservoir classification, which reveals their continuous distribution. These findings provide a geological foundation for evaluating "sweet spots" and testing the oil production in HSR reservoirs.