Huntington disease (HD) is an inherited disorder hallmarked by progressive deterioration of specific neurons, followed by movement and cognitive anomalies. Cell therapy approaches in neurodegenerative conditions have concentrated on the replenishment of lost/dying neurons with functional ones. Multipotent mesenchymal stem cells (MSCs) have been represented as a potential remedy for HD. In this study, we evaluated the in vitro and in vivo efficacy of umbilical cord matrix stem cells (UCMSCs) and their paracrine effect against oxidative stress with a specific focus on HD. To this end, UCMSCs were isolated, immunophenotypically characterized by the positive expression of MSC markers, and exhibited multilineage potentiality. Besides, synthesis of neurotrophic factors of GDNF and VEGF by UCMSC was confirmed. Initially, PC12 cells were exposed to superoxide in the presence of conditioned media (CM) collected from UCMSC (UCMSC-CM) and cell viability plus neuritogenesis were measured. Next, bilateral striatal transplantation of UCMSC in 3-nitropropionic acid (3-NP) lesioned rat models was conducted, and 1 month later, post-graft analysis was performed. According to our in vitro results, CM of UCMSC protected PC12 cells against oxidative stress and considerably enhanced cell viability and neurite outgrowth. On the other hand, transplanted UCMSC survived, decreased gliosis, and ameliorated motor coordination and muscle activity, along with an increase in striatal volume as well as in dendritic length of the striatum in HD rats. Collectively, our findings imply that UCMSCs provide an enriched platform by largely their paracrine factors, which downgrades the unfavorable effects of oxidative stress.
Adipose-derived stem cells (ADSCs) are a population of cells derived from adipose tissue. ADSCs exhibit multilineage development potential and are able to secrete various factors, which influence adjacent cells. The present study examined the protective effect of ADSC's conditioned media (ADSC-CM) on PC12 cells exposed to H2O2, an oxidative injury model. After isolation, ADSCs were cultured and their osteogenic and adipogenic differentiation confirmed. Then, PC12 cells were co-treated with ADSC-CM and H2O2. Next, the effects of ADSC-CM on neurite outgrowth and cell differentiation in the presence of H2O2 were determined. Moreover, cell viability and apoptotic cell death percentage were evaluated using MTT assay, Hoechst staining and flow cytometry. Our results indicated the neuroprotective effects of ADSC-CM on morphological and morphometrical properties of neuron-like PC12 cells. Additionally, the profound decrease in percentage of apoptotic cells confirmed the protective effects of conditioned media from ADSCs that may be related to the release of trophic factors.
In acute myeloid leukemia (AML), despite the acceptance of standard intensive chemotherapy as an optimal induction regimen for all age groups, in the elderly patients, the best treatment should meet the challenge of multiple factors like age, comorbidities, and cytogenetics, making them ineligible for standard induction chemotherapy. Using the current low-intensity therapies like decitabine, azacitidine, and low-dose cytarabine as a single arm, outcomes for these patients remain poor. As a histone deacetylase inhibitor valproic acid (VPA) exhibit anticancer activity by triggering apoptosis, the mechanism of which is not yet completely clarified. To explore the possible connection between VPA treatment and the Hippo pathway as an apoptosis stimulating route, we also explore the expression of major components of this pathway and for the first time we postulate a relationship between VPA treatment and cell death induction through RASSF1A expression induction. Furthermore, we demonstrate that autophagy inhibition by chloroquine (CQ) significantly augmented the cytotoxic effect of VPA on AML cells, especially in those with unfavorable and normal karyotype. Regarding that VPA and CQ are well-tolerated drugs and our presumptive results of usefulness of VPA + CQ in three cytogenetic risk groups of AML, this combinatorial therapy could represent an attractive treatment option for older AML patients unfit for intensive therapy.
Masonry buildings have a large share in the context of large and small towns, For example, in the city of Bam more than 90 percent of the buildings with brick and masonry structures, which are about 40% of the amount of masonry structures. According to reports, all masonry buildings are damaged in the earthquake of 20 to 100 percent. Research shows that the bulk of the damage to buildings caused by non-compliance with the provisions of the Building Regulations 2800, including the opening of the wall, the opening in the wall, resulting space restrictions, the wall of the building and etc. In this paper, a masonry structures under earthquake made great naqan modeling the structures in abaqus software in the form of macro, and the first to be connected and then a layer of sand sliding sought to separate the topside of the use and analyzed them. After this, the effect on the seismic behavior of the proposed system and create havoc in the corners of the openings are possible. Find answers to the two-state system; it is found that the proposed isolation system, while considerably reducing damage, the size of the openings can be considered more of a standard.
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