Increasing evidences implicate impairment of axonal integrity in mechanisms underlying neurodegenerative disorders. Beta-boswellic acid (BBA) is the major component of Boswellia serrata gum. This resin has long been used in Ayurveda (India's traditional medicine) to prevent amnesia. In this study, the effect of BBA was examined on neurites outgrowth and branching as well as on polymerization dynamics of tubulin. The morphometric parameters (axonal length and neuritis branching) were examined microscopically after treating the hippocampal cells with BBA. Also the assembly process of tubulin was assessed using UV/V is spectrophotometer through following of absorbance at 350 nm. The results revealed that BBA could significantly enhance neurite outgrowth, branching, and tubulin polymerization dynamics. The obtained results suggest that enhancing effect of BBA on microtubule polymerization kinetics might be the origin of increasing axonal outgrowth and branching.
a b s t r a c tHyperhomocysteinemia has recently been identified as an important risk factor for Alzheimer's disease (AD). One of the potential mechanisms underlying harmful effects of homocysteine (Hcy) is site-specific acylation of proteins at lysine residues by homocysteine thiolactone (HCTL). The accumulation of amyloid b-peptide (Ab) in the brain is a neuropathological hallmark of AD. In the present study we were interested to investigate the effects of N-homocysteinylation on the aggregation propensity and neurotoxicity of Ab 1-42 . By coupling several techniques, we demonstrated that the homocysteinylation of lysine residues increase the neurotoxicity of the Ab peptide by stabilizing soluble oligomeric intermediates.
Structured summary of protein interactions:A Beta 1-42 and A Beta 1-42 bind by fluorescence technology (View interaction) A Beta 1-42 and A Beta 1-42 bind by electron microscopy (View interaction)
Experimental autoimmune encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS) is characterized by demyelination, infiltration of inflammatory cells into the nervous system and dysregulation of serum inflammatory cytokines. We investigated the correlation of serum cytokines and other inflammatory markers with the EAE pathogenesis. After EAE induction, the levels of different serum cytokine/inflammatory mediators were measured. Furthermore, motor functions, myelination, and lymphocyte infiltration in EAE mice were also assessed. Our results revealed that the serum concentrations of Thelper 1 (Th1) and Th17 cytokines, interleukin (IL)-6, IL-1β, IL-1α and prostaglandin E2 in EAE mice were significantly higher than controls. The ratios of pro-to anti-inflammatory cytokines were different between the EAE and the control group. A statistically significant positive correlation was found between the IL-6/IL-10 ratio and the EAE severity, demyelination rate, and lymphocyte infiltration in EAE mice. Results indicate that the profiles of serum pro-and anti-inflammatory cytokines might be useful as biomarkers for monitoring the pathological manifestation of EAE. Furthermore, evaluating the dynamic interplay of serum cytokine levels and the correlation with pathogenic mechanisms of EAE may provide diagnostic and therapeutic insights for MS and some other inflammatory disorders.
Human induced pluripotent stem cells (hiPSCs) are attractive sources of cells for disease modeling in vitro, and they may eventually provide access to cells/tissues for the treatment of many degenerative diseases. Stepwise differentiation from hiPSCs to definitive endoderm (DE) will identify a key step in hepatocytes and beta cell development and may prove useful for transplantation therapy for liver diseases and diabetes. Inducer of definitive endoderm 1 (IDE1) is known to play an important role in the regional specification of DE. Here, we have investigated the effect of stimulation with IDE1 on the development of hiPSCs into DE cells in three-dimensional (3D) cultures. The differentiation was determined by immunofluorescence staining with Sox17, FoxA2, and goosecoid (Gsc) and also by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis. In this study, we showed that hiPSCs with 6-day IDE1 treatment (as chemical tool) on poly(ε-caprolactone) (PCL) nanofibrous scaffold were able to differentiate into DE cells.
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