Current Issue : January - March Volume : 2021 Issue Number : 1 Articles : 5 Articles
Moscatilin can protect rat pheochromocytoma cells against methylglyoxal-induced damage.\nElimination of the effect of advanced glycation end-products (AGEs) but activation of AMP-activated\nprotein kinase (AMPK) are the potential therapeutic targets for the neurodegenerative diseases.\nOur study aimed to clarify AMPK signalingâ??s role in the beneficial effects of moscatilin on the\ndiabetic/hyperglycemia-associated neurodegenerative disorders. AGEs-induced injury in SH-SY5Y\ncells was used as an in vitro neurodegenerative model. AGEs stimulation resulted in cellular\nviability loss and reactive oxygen species production, and mitochondrial membrane potential collapse.\nIt was observed that the cleaved forms of caspase-9, caspase-3, and poly (ADP-ribose) polymerase\nincreased in SH-SY5Y cells following AGEs exposure. AGEs decreased Bcl-2 but increased Bax\nand p53 expression and nuclear factor kappa-B activation in SH-SY5Y cells. AGEs also attenuated\nthe phosphorylation level of AMPK. These AGEs-induced detrimental effects were ameliorated by\nmoscatilin, which was similar to the actions of metformin. Compound C, an inhibitor of AMPK,\nabolished the beneficial effects of moscatilin on the regulation of SH-SY5Y cellsâ?? function, indicating\nthe involvement of AMPK. In conclusion, moscatilin offers a promising therapeutic strategy to\nreduce the neurotoxicity or AMPK dysfunction of AGEs. It provides a potential beneficial effect with\nAGEs-related neurodegenerative diseases....
Background: The complement cascade is increasingly implicated in development of a variety of diseases with\nstrong immune contributions such as Alzheimerâ??s disease and Systemic Lupus Erythematosus. Mouse models have\nbeen used to determine function of central components of the complement cascade such as C1q and C3.\nHowever, species differences in their gene structures mean that mice do not adequately replicate human\ncomplement regulators, including CR1 and CR2. Genetic variation in CR1 and CR2 have been implicated in\nmodifying disease states but the mechanisms are not known.\nResults: To decipher the roles of human CR1 and CR2 in health and disease, we engineered C57BL/6J (B6) mice to\nreplace endogenous murine Cr2 with human complement receptors, CR1 and CR2 (B6.CR2CR1). CR1 has an array of\nallotypes in human populations and using traditional recombination methods (Flp-frt and Cre-loxP) two of the most\ncommon alleles................................
To characterize the tumor extracellular matrix (ECM) using native T1 mapping magnetic\nresonance imaging (MRI) in an experimental hepatic cancer model, a total of 27 female New Zealand\nwhite rabbits with hepatic VX2 tumors were examined by MRI at different time points following tumor\nimplantation (day 14, 21, 28). A steady-state precession readout single-shot MOLLI sequence was\nacquired in a 3 T MRI scanner in prone position using a head-neck coil. The tumors were segmented\ninto a central, marginal, and peritumoral region in anatomical images and color-coded T1 maps.\nIn histopathological sections, stained withH&Eand; Picrosirius red, the regions corresponded to central\ntumor necrosis and accumulation of viable cells with fibrosis in the tumor periphery. Another region\nof interest (ROI) was placed in healthy liver tissue. T1 times were correlated with quantitative data of\ncollagen area staining. A two-way repeated-measures ANOVA was used to compare cohorts and\ntumor regions. Hepatic tumors were successfully induced in all rabbits. T1 mapping demonstrated\nsignificant differences between the different tumor regions........................................
The EphA2 tyrosine kinase receptor is highly expressed in several types of solid tumors.\nIn our recent studies, we targeted EphA2 in pancreatic cancer with agonistic agents and demonstrated\nthat suppression of EphA2 significantly reduced cancer-cell migration in cell-based assays. In the\npresent study, we focused on targeting EphA2 in prostate cancer. While not all prostate cancers\nexpress EphA2, we showed that enzalutamide induced EphA2 expression in prostate cancer cells\nand in a patient-derived xenograft (PDX) animal model, which provides further impetus to target\nEphA2 in prostate cancer. Western blot studies showed that agonistic dimeric synthetic (135H12)\nand natural (ephrinA1-Fc) ligands effectively degraded EphA2 receptor in the prostate cancer cell\nline PC-3. The agents also delayed cell migration of prostate cancer (PC-3) cells, while an in vivo\nPC-3 orthotopic metastatic nude-mouse model also revealed that administration of ephrinA1-Fc or\n135H12 strongly reduced metastases. The present study further validates EphA2 as an important\ntarget in metastatic prostate cancer treatment. Our results should incentivize further efforts aimed at\ndeveloping potent and effective EphA2 synthetic agonistic agents for the treatment of EphA2-driven\naggressive metastatic tumors including prostate, pancreatic, and breast cancer....
Parkinsonâ??s disease (PD) is the second most common neurodegenerative disease, which is\nclinically and pathologically characterized by motor dysfunction and the loss of dopaminergic\nneurons in the substantia nigra, respectively. PD treatment with stem cells has long been studied by\nresearchers; however, no adequate treatment strategy has been established. The results of studies so\nfar have suggested that stem cell transplantation can be an effective treatment for PD. However, PD is\na progressively deteriorating neurodegenerative disease that requires long-term treatment, and this\nhas been insufficiently studied. Thus, we aimed to investigate the therapeutic potential of human\nadipose-derived stem cells (hASC) for repeated vein transplantation over long-term in an animal\nmodel of PD. In 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice,\nhASCs were administered on the tail vein six times at two-week intervals. After the last injection of\nhASCs, motor function significantly improved. The number of dopaminergic neurons present in the\nnigrostriatal pathway was recovered using hASC transplantation. Moreover, the administration of\nhASC restored altered dopamine transporter expression and increased neurotrophic factors, such as\nbrain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF), in the\nstriatum.....................
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