Differential gene expression by RNA-seq during Alzheimer's disease-like progression in the Drosophila melanogaster model.

Alzheimer's disease (AD) is characterized by progressive, irreversible loss of memory and cognitive function. Drosophila melanogaster and other animal models are used to study several diseases, in order to elucidate unknown mechanisms and develop potential therapies. Molecular studies require biological samples and, for neuropathologies such as AD biopsy of the human brain, are invasive and potentially damaging. The solution is to use animal models, such as D. melanogaster, which is a model organism that can replace mammalian organisms in such studies. In this study, we evaluated the climbing ability and differential gene expression during AD progression due to the amylodoigenic pathway using RNA-seq, and we performed an in silico analysis of a fruit fly AD-like GFP (Green Fluorescent Protein) model with GFP expression in the pan-neural elav driver. A total of 1388 genes were differentially expressed in all analyzed groups. The main pathways related to those Differentially Expressed Genes (DEGs) during aging and AD progression were evaluated using the fly genes and human orthologs, in order to link genomic information to higher-order functional information with gene pathway mapping. We identified pathways present in all analyzed groups, such as metabolic pathways, ribosomal pathways, proteasome pathways and immune system pathways. Some of the genes were validated by qPCR. Knockdown of CG17754 gene by RNAi promoted degeneration in the fly eye, validating these findings in vivo. The identification of similarities in molecular pathways between the transgenic fly AD-like GFP model and mammals related to AD provides new insights into the use of this fly in screening novel anti-AD drugs.

Endogenous galectin-3 is required for skeletal muscle repair.

Skeletal muscle has the intrinsic ability to self-repair through a multifactorial process, but many aspects of its cellular and molecular mechanisms are not fully understood. There is increasing evidence that some members of the mammalian ß-galactoside-binding protein family (galectins) are involved in the muscular repair process (MRP), including galectin-3 (Gal-3). However, there are many questions about the role of this protein on muscle self-repair. Here, we demonstrate that endogenous Gal-3 is required for: (i) muscle repair in vivo by using a chloride-barium myolesion mouse model and (ii) mouse primary myoblasts myogenic programming. Injured muscle from Gal-3 knockout mice (GAL3KO) showed persistent inflammation associated with compromised muscle repair and the formation of fibrotic tissue on the lesion site. In GAL3KO mice, osteopontin expression remained high even after 7 and 14 d of the myolesion, while Myoblast differentiation transcription factor (MyoD) and myogenin had decreased their expression. In GAL3KO mouse primary myoblast cell culture, Paired Box 7 (Pax7) detection seems to sustain even when cells are stimulated to differentiation and MyoD expression is drastically reduced. The detection and temporal expression levels of these transcriptional factors appear to be altered in Gal-3-deficient myoblast. Gal-3 expression in wild-type mice for GAL3KO states, both in vivo and in vitro, in sarcoplasm/cytoplasm and myonuclei; as differentiation proceeds, Gal-3 expression is drastically reduced, and its location is confined to the sarcolemma/plasma cell membrane. We also observed a change in the temporal-spatial profile of Gal-3 expression and muscle transcription factors levels during the myolesion. Overall, these results demonstrate that endogenous Gal-3 is required for the skeletal muscle repair process.

Different Gene Therapy Strategies: A Overview for Prostate Cancer.

Gene therapy emerged as a mighty alternative for conventional treatment of multiple diseases. It has been defined as a product "that mediate their effects by transcription and/or translation of transferred genetic material and/or by integrating into the host genome and that are administered as nucleic acids, viruses, or genetically engineered microorganisms. The products may be used to modify cells in vivo or transferred to cells ex vivo prior to administration to the recipient". The first therapeutic gene therapy human trial was conducted in 1990 by Michael R. Blaese, and besides its potential, the technique suffered a major drawback after the tragical death of Jesse Gelsinger, caused by his immune response against the viral vector used in his treatment. To date, gene therapy has regained some popularity and more than 2000 clinical trials are ongoing, most of them related to the treatment or prevention of various types of cancer. Nevertheless, some types of cancer contain a rare population of stem-like cells, capable of differentiation into tumor cells, promoting the re-incidence of tumors. Those cells are generally more resilient to chemotherapy and radiotherapy and are related to tumor initiation, progression, recurrence and metastasis. The human prostate cancer (PCa) is highly heterogeneous and multifactorial, and even the markers are not precise enough to predict the clinical outcome. Furthermore, even though currently therapies can efficiently remove the tumors, the re-incidence rates are high. Gene therapy offers a handful of treatments that can halt oncogenes activation, promote the expression of suppressor genes or target cancer cells directly and induce apoptosis. Besides the risks involved, gene therapy can be of great help in the treatment of cancers and other diseases. This review aims to address the safety and potential of different gene therapy strategies used in the treatment of cancers.