Study of the effect of bacterial lipopolysaccharide on the structure and dynamics on mouse tubulin polymerization

Background and aims: In recent decades, there has been much research on the microtubule dynamics as well as on factors affecting it. According to different studies, lipopolysaccharide (LPS) is thought to play an indirect role in neurodegenerative diseases through enzymatic pathways which hyperphosphorylate Tau protein and dissociate it from microtubules. In the present study, it was aimed to assess the direct effect of LPS on the structure and dynamics of tubulin polymerization in vitro. Methods: In this study, mouse tubulins were purified through two cycles of temperature-dependent polymerization-depolymerization. Cellulose-phosphate chromatography was used to further purify tubulins. SDS-PAGE was used to analyze the purity of the tubulins. Circular dichroism (CD), intrinsic fluorescence and turbidity assays were used to assess the changes in secondary and tertiary structures, and the dynamics of tubulin polymerization in the presence of different concentrations of LPS (5pM, 5nM, 50nM, 0.5µM and 5µM), respectively. Results: SDS-PAGE analysis confirmed the purity of tubulins. The intrinsic fluorescence analysis and CD assay revealed the changes in the secondary and tertiary structures of tubulins in the presence of LPS. The results of turbidity assay indicated that LPS could reduce the polymerization of tubulins. Conclusion: Our results indicate that LPS is able to change the secondary and tertiary structures of tubulin and decreases tubulin polymerization. According to our results, lipopolysaccharide in addition to an indirect effect on the microtubules stability, as well as by decreases in tubulin polymerization could result in neurodegenerative diseases specially Alzheimer's diseases

Longitudinal proxy measurements in multiple sclerosis: patient-proxy agreement on the impact of MS on daily life over a period of two years

Background: The use of self- report measurements in clinical settings is increasing. However, in patients with limitations that interfere with reliable self- assessment such as cognitive impairment or mood disturbances, as may be the case in multiple sclerosis ( MS), data collection might be problematic. In these situations, information obtained from proxy respondents ( e. g. partners) may replace self- ratings. The aim of this study was to examine the value of proxy ratings at separate points in time and to assess patient- proxy agreement on possible changes in disease impact of MS. Methods: Fifty- six MS patients and their partners completed the Multiple Sclerosis Impact Scale ( MSIS- 29) at baseline and follow- up, two years later. Patient- proxy agreement was assessed at both time points by calculating intraclass correlation coefficients ( ICCs), exact and global agreement and the mean directional differences between groups. Agreement of change over time was assessed by calculating ICCs between change scores. In parallel, global ratings of both patients and proxy respondents of the extent to which the patient had improved or deteriorated over the past two years were collected to validate possible changes on the MSIS- 29. Results: At both time points, agreement on the physical scale was higher than agreement on the psychological scale ( ICCs at baseline were 0.81 for the physical scale and 0.72 for the psychological scale; at follow- up, the ICC values were 0.86 and 0.65 respectively). At follow- up, statistically significant mean differences between patients and proxies were noted for the physical scale (- 4.8 +/- 12.7, p = 0.006) and the psychological scale (- 8.9 +/- 18.8, p = 0.001). Agreement between change scores on the MSIS- 29 was fair ( ICC < 0.60). Our analyses suggest that the validity of measuring changes over time might be better for proxy respondents compared to patients. Conclusion: Proxy respondents could act as a reliable source of information in cross- sectional studies. Moreover, results suggested that agreement on change over time might be better for proxy respondents compared to patients. Although this remarkable finding should be interpreted cautiously because of several limitations of the study, it does plead for further investigation of this important topic

The Study of Prevalence of Low Birth Weight Newborns in Hamadan&apos;s Meternity Hospitals During The First 9 Months of 1974

The study of Prevalence of Low Birth Weight newborns in Hamadan&apos;s Maternity hospitals during the first 9 months in 1374.The purpose of this study was to ascertain the prevalence of low birth weight infants in Hamadan. For this reason the whole births during the first 9 months in year 1374 in Hamadan&apos;s maternity hospitals was studied and each of LEW infant was Considered as a &amp;quot;Case&amp;quot;. Inspite of each LBW, two babies with normal weight was selected as Control group. The total number of records which were studied were 9145. Results showed that the prevalence of LBW is 10.8% . The statistical tests indicates that there is association between the newborn&apos;s weight and the type of pregnancy (Singleton or multiple), mother&apos;s age, gravidity and maternal disease.(P&amp;lt;0.0001). No relationship was found between the newborn&apos;s sex and his or her weight at birth

Effects of Allium hirtifolium (Iranian shallot) and its allicin on microtubule and cancer cell lines

Allium hirtifolim Boiss. (Iranian Shallot) belongs to Allium genus (Alliaceae family). Microtubule proteins (MTs) are crucial in maintenance of cell shape as well as cell division and mitosis. The present study aims at defining the anti-microtubule activities of A. hirtifolium and its allicin and examining itseffects on nerve cell microtubules. MTs were prepared from sheep brain through two cycles of polymerization and depolymerization. The cell growth inhibition was measured by 3-(4,5-dimethylthiazol 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) after treatment with A. hirtifolium and its allicin on HeLa and MCF-7 and L-929 cell lines. A. hirtifolium displayed growth inhibitory activity against HeLa and MCF-7 cells with IC (50) value of 20 and 24 mg/L, respectively, for 72 h and obviously showed cellgrowth inhibition on these cell lines at non-toxic concentration (lower than 1 g/L). Inhibition of MTs polymerization induced by A. hirtifolium and its ability to bind to tubulin as a ligand was tested through turbidimetry assay then investigated by Transmission Electron Microscopy (TEM). The concentration of A. hirtifolium necessary to inhibit the assembly of MTs by 50% was 1.2 g/L, while an inhibition higher than 80% was observed in the presence of 4 g/L of A. hirtifolium. This plant decreased MTspolymerization; therefore we suggest A. hirtifolium can be an effective ligand for cancer therapy

Extending the application of a magnetic PEG three-part drug release device on a graphene substrate for the removal of Gram-positive and Gram-negative bacteria and cancerous and pathologic cells

M Ramezani Farani,1 P Khadive Parsi,1 Gh Riazi,2 M Shafiee Ardestani,3 H Saligeh Rad4,5 1School of Chemical Engineering, University College of Engineering, University of Tehran, Tehran 4563-11155, Iran; 2Institute of Biophysics and Biochemistry, University of Tehran, Tehran 1417614411, Iran; 3Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; 4Quantitative Medical Imaging Systems Group, Research Center for Molecular and Cellular Imaging, Tehran University of Medical Sciences, Tehran, Iran; 5Medical Physics and Biomedical Engineering Department, Tehran University of Medical Sciences, Tehran, Iran Objective: In this study, novel graphene oxide (GO)-based nanocomposites are presented. In fact, we have tried to replace the carboxyl groups on the surface of GO with amine groups to allow the biocompatible poly(ethylene glycol) bis(carboxymethyl) ether (average Mn 600) polymer to bond through an amide bond. Materials and methods: The synthesis was conducted accurately according to final characterization experiments (Raman, X-ray diffraction [XRD], atomic force microscopy [AFM], X-ray photoelectron spectroscopy [XPS], thermogravimetric analysis [TGA], etc). The antimicrobial property of this nanocomposite was examined in Escherichia coli (ATCC 25922) as Gram-negative and Staphylococcus aureus (ATCC 25923) as Gram-positive bacterial species. Besides, curcumin (CUR) was added to the produced nanocomposite both as a promising anticancer drug and an antioxidant, the toxicity of which was then assessed on cellular-based HepG2 and pC12. Results: An intense increase in toxicity was detected by MTT assay. Conclusion: It can mainly be concluded that the nanocomposite synthesized in this study is capable of delivering drugs with antibacterial properties. Keywords: graphene oxide, magnetic nanocomposite, drug delivery, antimicrobial, curcumi