Evaluating cytotoxic effect of nanoliposomes encapsulated with umbelliprenin on 4T1 cell line

Cytotoxicity of umbelliprenin has been found in various cancer cell lines such as, prostate, breast, CLL, and skin. Encapsulating chemotherapeutic agents with nanoliposomes have been resulted in improved cytotoxicity effects than their free forms. However, whether nanoliposomal form of umbelliprenin could have higher cytotoxic effect than free umbelliprenin is not clarified yet. After synthesizing umbelliprenin, different concentrations (3, 6, 12, 25, 50, 100, 200 μg/ml) applied on the mouse mammary carcinoma cell line (4T1) for 24, 48, and 72 h at 37°C. Afterwards, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was performed to analyze cytotoxicity. MTT assay results showed that IC₅₀ of umbelliprenin in dimethyl sulfoxide (DMSO) (30.92, 30.64, and 62.23 for 24, 48, 72 h incubation, respectively) decreased (5.8, 5.0, 3.5 for 24, 48, 72 h incubation, respectively) when encapsulated with nanoliposomes. Nanoliposomal umbelliprenin cytotoxicity affected cell viability in concentration and time-dependent manner. Our study recommended nanoliposomal umbelliprenin as the most effective chemotherapeutic agent against the mouse mammary carcinoma cell line viability. Future in vivo studies and clinical trials are needed.     

Rapid suppression and sustained activation of distinct cortical regions for a delayed sensory-triggered motor response

1. Download : Download high-res image (164KB)
2. Download : Download full-size image

     

Small molecule Y-320 stimulates ribosome biogenesis,protein synthesis,and aminoglycoside-induced premature termination codon readthrough

Premature termination codons (PTC) cause over 10% of genetic disease cases. Some aminoglycosides that bind to the ribosome decoding center can induce PTC readthrough and restore low levels of full-length functional proteins. However, concomitant inhibition of protein synthesis limits the extent of PTC readthrough that can be achieved by aminoglycosides like G418. Using a cell-based screen, we identified a small molecule, the phenylpyrazoleanilide Y-320, that potently enhances TP53, DMD, and COL17A1 PTC readthrough by G418. Unexpectedly, Y-320 increased cellular protein levels and protein synthesis, measured by SYPRO Ruby protein staining and puromycin labeling, as well as ribosome biogenesis measured using antibodies to rRNA and ribosomal protein S6. Y-320 did not increase the rate of translation elongation and it exerted its effects independently of mTOR signaling. At the single cell level, exposure to Y-320 and G418 increased ribosome content and protein synthesis which correlated strongly with PTC readthrough. As a single agent, Y-320 did not affect translation fidelity measured using a luciferase reporter gene but it enhanced misincorporation by G418. RNA-seq data showed that Y-320 up-regulated the expression of CXC chemokines CXCL10, CXCL8, CXCL2, CXCL11, CXCL3, CXCL1, and CXCL16. Several of these chemokines exert their cellular effects through the receptor CXCR2 and the CXCR2 antagonist SB225002 reduced cellular protein levels and PTC readthrough in cells exposed to Y-320 and G418. These data show that the self-limiting nature of PTC readthrough by G418 can be compensated by Y-320, a potent enhancer of PTC readthrough that increases ribosome biogenesis and protein synthesis. They also support a model whereby increased PTC readthrough is enabled by increased protein synthesis mediated by an autocrine chemokine signaling pathway. The findings also raise the possibility that inflammatory processes affect cellular propensity to readthrough agents and that immunomodulatory drugs like Y-320 might find application in PTC readthrough therapy.

A cell-based screen identifies a small molecule, Y-320, that potently enhances readthrough of premature termination codons by the aminoglycoside G418. Y-320 increases cellular protein levels and protein synthesis, and appears to act via an autocrine chemokine signaling pathway.     

Association study of rs10768683 and rs968857 polymorphisms with transfusion-dependent thalassemia (TDT) in a southern Iranian population

Previous studies reported that detection of polymorphisms inherited through paternal model could be potential markers for the Non-Invasive Prenatal Diagnosis (NIPD) of β-thalassemia. The aim of the current study was to find out the associations of rs10768683 and rs968857 with transfusion-dependent thalassemia (TDT) in a southern Iranian population. A total of 175 subjects were investigated, divided into patients with TDT as case group (n?=?75) and healthy people as control group (n?=?100). Genomic DNAs were extracted from peripheral blood using salting out procedure. Genotyping rs10768683 and rs968857 was carried out by ARMS-PCR, then statistical analyses were assessed using SPSS, and Medcalc ver. 18 software. Data showed that rs10768683 was statistically significant in co-dominant model of inheritance (P?=?0.025, OR?=?2.11 [1.08-4.15]) and genotype frequencies of CG among controls and cases were 0.68 and 0.80, respectively. However, according to genotype frequencies, there was no association between rs968857 and TDT among cases and healthy controls in any models of inheritance. In conclusion, the present study showed the association of rs10768683 with major β-thalassemia through ARMS-PCR technique.     

Retinoic Acid Correlates with Reduced Serum IL-10 And TGF-β in Allergic Rhinitis

Background:Retinoic acid (RA) plays a key role in naïve T cell differentiation into FOXP3+ Treg cell in the respiratory airways. The present study aims to investigate RA and Treg-related cytokine serum levels, salivary IgA levels, FOXP3 and IL-4 gene expression, and the relationships between RA serum levels and Treg-related cytokines in allergic rhinitis (AR) patients and healthy controls.Methods:Salivary IgA and serum IgE, RA, IL-10, and TGF-β concentrations were measured by ELISA in 37 AR patients and 30 age- and sex-matched healthy controls.Results:IL-10 and TGF-β concentrations were significantly less in AR patients than in healthy controls (p< 0.01 and P< 0.0001, respectively). Salivary IgA was significantly greater in patients than in controls (p< 0.05). RA was not significantly different between patients and controls (p> 0.05); however, a significant positive correlation was found between serum RA and both IL-10 and TGF-β in AR patients.Conclusion:Our data suggest that RA may influence AR risk via affecting the TGF-β and IL-10 production.Key Words: Allergic Rhinitis, Interleukin-10, Obesity, Retinoic Acid, Transforming Growth Factor-β     

Effect of hydration on assessment of early enamel lesion using swept‐source optical coherence tomography

Establishing reproducible methodologies for assessment of early enamel lesions using optical coherence tomography (OCT) appears to be challenging. This in vitro study longitudinally evaluated the subsurface enamel lesion progression after 3, 9 and 15 days by cross‐sectional scanning using 1310 nm centered swept‐source OCT (SS‐OCT) under hydrated and dry conditions. The positive difference between the depth‐integrated OCT signals at dry and hydrated conditions were calculated and adopted as dehydration parameter (DH). A linear regression was found between DH and the square root of demineralization time (R² = 0.99). Significant differences were found in DH between sound and demineralized enamel, and between different periods of demineralization (p < 0.001). Hydration state affects the reflectivity of demineralized porous enamel, and the effect can be potentially used for assessment of early enamel lesion using OCT. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)