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Intracellular Trafficking Mechanisms of Synaptic Dysfunction in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by progressive memory loss. Although AD neuropathological hallmarks of extracellular amyloid plaques and intracellular tau tangles, which best correlates of disease progression is the loss of synapses. What causes the loss of synapses have been the focus of some researcher s in the field of AD. Synapses become dysfunctional before the plaques and tangles form.  The study is based on the model of early-onset familial AD (eFAD) has supported that synaptic transmission depressed by β-amyloid (Aβ) triggered mechanism. Since eFAD rare, affecting only 1% of patients, research has shifted to the study of the most PBS  common late-onset AD (LOAD). intracellular trafficking has emerged as one of the pathways of gene LOAD.  Several studies have assessed the impact of gene LOAD trading on synapse dysfunction. Because the endocytic traffic is very important for synaptic function, we review the mechani...
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A Coupled Mathematical Model of the Intracellular Replication of Dengue Virus and the Host Cell Immune Response to Infection.

Dengue virus (DV) is a positive-strand viral RNA of the genus flavivirus. It is one of the most prevalent virus mosquitoes, infects 390 million people globally per year. DV infection clinical spectrum ranges from asymptomatic course of severe complications such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), the latter due to a severe plasma leakage.  Given that the outcome of an infection may be determined by the kinetics of viral replication and antiviral host cell immune response (HIR) it is very important to understand the interaction between the two parameters. In this study, we used a mathematical model to characterize and understand the complex interactions between DV intracellular replication and host cell's defense mechanisms. We first measured the viral RNA, viral proteins, and the production of virus particles in Huh7 cells, which indicates the intrinsic antiviral responses are notoriously weak. Based on these measurements, we developed a detailed int...

Chitosan-Based Nanoparticles for Intracellular Delivery of ISAV Fusion Protein cDNA into Melanoma Cells: A Path to Develop Oncolytic Anticancer Therapies.

Oncolytic virus therapy has been tested against cancer in preclinical models and clinical tests. Evidence suggests today that the virus caused cytopathic effects associated with the formation of protein-mediated syncytium fusogenik and immunogenic cell death of eukaryotic cells. We have previously shown that the body of tumor cells generated from cells that express the protein fusogenik infectious salmon anemia virus ( ISAV-F) increase crosspriming and display antitumor activity against melanoma tumor prophylaxis.  In this work, we evaluated the effect of the expression of ISAV-F on B16 melanoma model, both in vitro and in vivo, using chitosan nanoparticles as transfection vehicle. We confirmed that the B16 tumor array  cell transfection with chitosan nanoparticles (NP-ISAV) allows the expression of proteins ISAV-F fusogenically active and reduced cell viability for syncytium formation in vitro.  However, in vivo transfection induced delay in tumor growth, without a chang...

Proteoglycan-Dependent Endo-Lysosomal Fusion Affects Intracellular Survival of Salmonella Typhimurium in Epithelial Cells.

Proteoglycans (PG) which glycoconjugates predominantly expressed on the cell surface and consists of glycosaminoglycans (GAGs) are linked to core proteins. The initial step of the assembly GAG regulated by the enzyme β-D-xylosyltransferase encoded in mammals with XylT1 / XylT2 genes. PG is essential for cell interaction with other cells and with the extracellular matrix.  Numerous studies have highlighted the role of PG in bacterial adhesion, invasion, and immune response. In this work, we investigated the role of PG in Salmonella enterica serovar Typhimurium (S. Typhimurium) infection of epithelial cells. gentamicin protection test and chloroquine resistance are applied to judge the invasion and replication in wild-type S. Typhimurium and xylosyltransferase-deficiency (ΔXylT2) Chinese hamster ovary (CHO) cells lacking PG.  We found that S. Typhimurium embrace and attack the cells of WT and CHO CHO ΔXylT2 at comparable rates. However, 24 hours after infection, cells proteoglyc...

Nanoparticle-Mediated Intracellular Protection of Natural Killer Cells Avoids Cryoinjury and Retains Potent Antitumor Functions.

The ability of natural killer (NK) cells to mediate potent antitumor immunity in clinical adoptive transfer arrangement depends, in large part, on their ability to maintain function following cytotoxic cryopreservation. To avoid potential systemic toxicity associated with NK cell infusion to the patient in the presence of dimethylsulfoxide (DMSO ), interest in alternative cryoprotective agent (CPA) with improved safety profile has grown.  Although the development of a variety of sugars, amino acids, polyols, and polyampholytes as cryoprotectant, their ability to promote the protection of intracellular cryodamage limited as they mostly act outside the cell. Although the shuttle intracellular cryoprotectant way there, high aversity NK cells for manipulation and freezing means that they are very understudied as a target for the development of new cryopreservation approach. Here, the first example of a platform that is safe and efficient for intracellular delivery of non-DMSO CPA pres...

Heterogeneous Strategies to Eliminate Intracellular Bacterial Pathogens.

tolerance of antibiotics on bacterial pathogens that are genetically susceptible, but phenotypically tolerant to treatment, is a growing crisis for public health. In particular, intracellular bacterial-mediated antibiotic tolerance by acting as a "Trojan horse" plays an important and underappreciated role in the burden of bacterial infectious diseases.  Thus, a more intense effort is needed to overcome this problem. In this review, we first give a brief description of the mode of action of bacterial invasion and survival in macrophages or non-professional phagocytes. Intracellular   In addition, we summarize our current knowledge on a promising strategy to eliminate these intracellular bacterial pathogens, including direct bactericidal =  Finally, we briefly discusses the challenges faced by bringing them into clinical trials and our constructive perspective. The main purification of intracellular water biphasic system Halomonas salina ectoine using ionic liquids based. E...