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81.
82.
Soheil Zorofchian Moghadamtousi Elham Rouhollahi Hamed Karimian Mehran Fadaeinasab Mohammad Firoozinia Mahmood Ameen Abdulla Habsah Abdul Kadir 《PloS one》2015,10(4)
Annona muricata has been used in folk medicine for the treatment of cancer and tumors. This study evaluated the chemopreventive properties of an ethyl acetate extract of A. muricata leaves (EEAML) on azoxymethane-induced colonic aberrant crypt foci (ACF) in rats. Moreover, the cytotoxic compound of EEAML (Annomuricin E) was isolated, and its apoptosis-inducing effect was investigated against HT-29 colon cancer cell line using a bioassay-guided approach. This experiment was performed on five groups of rats: negative control, cancer control, EEAML (250 mg/kg), EEAML (500 mg/kg) and positive control (5-fluorouracil). Methylene blue staining of colorectal specimens showed that application of EEAML at both doses significantly reduced the colonic ACF formation compared with the cancer control group. Immunohistochemistry analysis showed the down-regulation of PCNA and Bcl-2 proteins and the up-regulation of Bax protein after administration of EEAML compared with the cancer control group. In addition, an increase in the levels of enzymatic antioxidants and a decrease in the malondialdehyde level of the colon tissue homogenates were observed, suggesting the suppression of lipid peroxidation. Annomuricin E inhibited the growth of HT-29 cells with an IC50 value of 1.62 ± 0.24 μg/ml after 48 h. The cytotoxic effect of annomuricin E was further substantiated by G1 cell cycle arrest and early apoptosis induction in HT-29 cells. Annomuricin E triggered mitochondria-initiated events, including the dissipation of the mitochondrial membrane potential and the leakage of cytochrome c from the mitochondria. Prior to these events, annomuricin E activated caspase 3/7 and caspase 9. Upstream, annomuricin E induced a time-dependent upregulation of Bax and downregulation of Bcl-2 at the mRNA and protein levels. In conclusion, these findings substantiate the usage of A. muricata leaves in ethnomedicine against cancer and highlight annomuricin E as one of the contributing compounds in the anticancer activity of A. muricata leaves. 相似文献
83.
Cech PG Aebi T Abdallah MS Mpina M Machunda EB Westerfeld N Stoffel SA Zurbriggen R Pluschke G Tanner M Daubenberger C Genton B Abdulla S 《PloS one》2011,6(7):e22273
Background
This trial was conducted to evaluate the safety and immunogenicity of two virosome formulated malaria peptidomimetics derived from Plasmodium falciparum AMA-1 and CSP in malaria semi-immune adults and children.Methods
The design was a prospective randomized, double-blind, controlled, age-deescalating study with two immunizations. 10 adults and 40 children (aged 5–9 years) living in a malaria endemic area were immunized with PEV3B or virosomal influenza vaccine Inflexal®V on day 0 and 90.Results
No serious or severe adverse events (AEs) related to the vaccines were observed. The only local solicited AE reported was pain at injection site, which affected more children in the Inflexal®V group compared to the PEV3B group (p = 0.014). In the PEV3B group, IgG ELISA endpoint titers specific for the AMA-1 and CSP peptide antigens were significantly higher for most time points compared to the Inflexal®V control group. Across all time points after first immunization the average ratio of endpoint titers to baseline values in PEV3B subjects ranged from 4 to 15 in adults and from 4 to 66 in children. As an exploratory outcome, we found that the incidence rate of clinical malaria episodes in children vaccinees was half the rate of the control children between study days 30 and 365 (0.0035 episodes per day at risk for PEV3B vs. 0.0069 for Inflexal®V; RR = 0.50 [95%-CI: 0.29–0.88], p = 0.02).Conclusion
These findings provide a strong basis for the further development of multivalent virosomal malaria peptide vaccines.Trial Registration
ClinicalTrials.gov NCT00513669相似文献84.
Elucidating the chemical and biochemical applications of Citrus sinensis-mediated silver nanocrystal
Nurunnesa Siddiqui Abdulla Al Masum Md. Raihan Uddin Sukhendu Mandal Mohana Sengupta 《Journal of biomolecular structure & dynamics》2013,31(18):4863-4874
AbstractSynthesis of nanoparticles using biodegradable source is safer and echo-friendly. Here, we describe the synthesis of polycrystalline silver nanocrystals using Citrus sinensis acting as both reducing and capping agents. After exposing the silver ions to orange extract, rapid reduction of silver ions led to the formation of stable silver nanocrystals due to the reducing and stabilizing properties of orange fruit juice. The synthesized silver nanocrystals were characterized using various analytical techniques like UV–vis spectroscopy, X-ray diffraction (XRD), dynamic light scattering (DLS), scanning electron microscope (SEM) and transmission electron microscopy (TEM). The biochemical activity of the synthesized nanocrystals was studied in the light of affinity to bovine serum albumin using several biophysical methods like absorbance, fluorescence and circular dichroism spectroscopy. Cytotoxic activity of these nanocrystals was also studied against Hep-2 cell line using fluorescence microscopy. It was also found that the synthesized nanocrystals can sense mercuric ion down to 50?µM in the presence of a number of cations. Furthermore, we established that the silver nanoparticles can effectively catalyse the reduction of methylene blue by ascorbic acid. The present study will enrich our knowledge on the chemical and biochemical activities of green-synthesized silver nanocrystals. 相似文献
85.
Mohammad Saud Alanazi Narasimha Reddy Parine Jilani Purusottapatnam Shaik Huda A. Alabdulkarim Sana Abdulla Ajaj Zahid Khan 《PloS one》2013,8(3)
Breast cancer is a complex heterogeneous disease involving genetic and epigenetic alterations in genes encoding proteins that are components of various signaling pathways. Candidate gene approach have identified association of genetic variants in the Wnt signaling pathway genes and increased susceptibility to several diseases including breast cancer. Due to the rarity of somatic mutations in key genes of Wnt pathway, we investigated the association of genetic variants in these genes with predisposition to breast cancers. We performed a case-control study to identify risk variants by examining 15 SNPs located in 8 genes associated with Wnt signaling. Genotypic analysis of individual locus showed statistically significant association of five SNPs located in β-catenin, AXIN2, DKK3, SFRP3 and TCF7L2 with breast cancers. Increased risk was observed only with the SNP in β-catenin while the other four SNPs conferred protection against breast cancers. Majority of these associations persisted after stratification of the cases based on estrogen receptor status and age of on-set of breast cancer. The rs7775 SNP in exon 6 of SFRP3 gene that codes for either arginine or glycine exhibited very strong association with breast cancer, even after Bonferroni''s correction. Apart from these five variants, rs3923086 in AXIN2 and rs3763511 in DKK4 that did not show any association in the overall population were significantly associated with early on-set and estrogen receptor negative breast cancers, respectively. This is the first study to utilize pathway based approach to identify association of risk variants in the Wnt signaling pathway genes with breast cancers. Confirmation of our findings in larger populations of different ethnicities would provide evidence for the role of Wnt pathway as well as screening markers for early detection of breast carcinomas. 相似文献
86.
Parental participation is a key factor in the prevention and management of childhood obesity, thus parental recognition of weight problems is essential. We estimated parental perceptions and their determinants in the Emirati population. We invited 1541 students (grade 1–12; 50% boys) and their parents, but only 1440 (6–19 years) and their parents consented. Of these, 945 Emirati nationals provided data for analysis. Anthropometric and demographic variables were measured by standard methods. CDC BMI percentile charts for age and sex were used to classify children’s weight. Parental perception of their children’s weight status (underweight, normal, and overweight/obese) was recorded. Logistic regression analyses were used to identify independent predictors of parental perceptions of children’s weight status. Of all parents, 33.8% misclassified their children’s’ weight status; underestimating (27.4%) or overestimating (6.3%). Misclassification was highest among parents of overweight/obese children (63.5%) and underweight (55.1%) children. More importantly, parental perceptions of their children being overweight or obese, among truly overweight/obese children, i.e. correct identification of an overweight/obese child as such, were associated with the true child’s BMI percentile (CDC) with an OR of 1.313 (95% CI: 1.209–1.425; p<0.001) per percentile point, but not age, parental education, household income, and child’s sex. We conclude that the majority of parents of overweight/obese children either overestimated or, more commonly, underestimated children’s weight status. Predictors of accurate parental perception, in this population, include the true children’s BMI, but not age, household income, and sex. Thus, parents having an incorrect perception of their child’s weight status may ignore otherwise appropriate health messages. 相似文献
87.
Tariq M. Butt Bethany P. J. Greenfield Carolyn Greig Thierry G. G. Maffeis James W. D. Taylor Justyna Piasecka Ed Dudley Ahmed Abdulla Ivan M. Dubovskiy Inmaculada Garrido-Jurado Enrique Quesada-Moraga Mark W. Penny Daniel C. Eastwood 《PloS one》2013,8(12)
Metarhizium anisopliae, a fungal pathogen of terrestrial arthropods, kills the aquatic larvae of Aedes aegypti, the vector of dengue and yellow fever. The fungus kills without adhering to the host cuticle. Ingested conidia also fail to germinate and are expelled in fecal pellets. This study investigates the mechanism by which this fungus adapted to terrestrial hosts kills aquatic mosquito larvae. Genes associated with the M. anisopliae early pathogenic response (proteinases Pr1 and Pr2, and adhesins, Mad1 and Mad2) are upregulated in the presence of larvae, but the established infection process observed in terrestrial hosts does not progress and insecticidal destruxins were not detected. Protease inhibitors reduce larval mortality indicating the importance of proteases in the host interaction. The Ae. aegypti immune response to M. anisopliae appears limited, whilst the oxidative stress response gene encoding for thiol peroxidase is upregulated. Cecropin and Hsp70 genes are downregulated as larval death occurs, and insect mortality appears to be linked to autolysis through caspase activity regulated by Hsp70 and inhibited, in infected larvae, by protease inhibitors. Evidence is presented that a traditional host-pathogen response does not occur as the species have not evolved to interact. M. anisopliae retains pre-formed pathogenic determinants which mediate host mortality, but unlike true aquatic fungal pathogens, does not recognise and colonise the larval host. 相似文献
88.
Background:The aim of present study is to asset the IL-2 promoter gene (SNP -475) as a candidate gene for multiple sclerosis (MS) susceptibility.Methods:This study included 70 patients with relapsing – remitting multiple sclerosis (RRMS) and 50 healthy controls. Following the extraction of genomic DNA from peripheral blood, frequency of genotypes and alleles of SNP -475 was calculated using Restriction fragment length polymorphism-polymer chain reaction (RFLP-PCR) and then the results were analyzed statistically.Results:The results revealed the unusual ratio for the heterozygous (AT) was 1.6972 indicating that heterozygous patients were at higher risk of multiple sclerosis than wild homozygous (AA), and homomutant (TT). The results show protective role for - 475 IL-2 promoter among individuals with multiple sclerosis, (O.R: 0.4872; C.I. 95%: 0.1617- 1.4680) and (O.R: 0.9275; C.I. 95%: 0.2476 - 3.4745) for both AA and TT genotypes, respectively.Conclusion:Our results showed that in this population of Iraqi patients, the AT genotype / A allele of -475 IL-2 promoter gene SNP may include attributed factors for MS predisposition.Key Words: IL-2, Multiple sclerosis, PCR-RFLP SNP 相似文献
89.
90.
Adenovirus E1A proteins direct subcellular redistribution of Nek9, a NimA-related kinase 总被引:1,自引:0,他引:1
Pelka P Scimè A Mandalfino C Joch M Abdulla P Whyte P 《Journal of cellular physiology》2007,212(1):13-25
A monoclonal antibody raised against adenovirus E1A-associated cellular proteins recognized Nek9, a NimA-related protein kinase. Subcellular fractionation and immunofluorescence indicated that Nek9 was primarily cytoplasmic with a small portion located in the nucleus whereas E1A was primarily nuclear. Although co-immunoprecipitation experiments indicated that nuclear Nek9 interacted, directly or indirectly, with E1A, the major effect of E1A was to diminish the amount of Nek9 in the nucleus suggesting that E1A alters the subcellular distribution of Nek9 and that the interaction is transient. A Nek9 deletion mutant lacking a central RCC1-like domain interacted stably with E1A and accumulated in the nucleus in the presence of E1A, possibly representing an intermediate stage of the normally transient Nek9/E1A interaction. The interaction of Nek9 with E1A was dependent on the N-terminal sequences of E1A. Attempts to stably overexpress either Nek9 or the kinase-inactive mutant in various cell lines were unsuccessful; however, the presence of E1A allowed stable overexpression of both proteins. These results suggest that E1A disrupts a nuclear function of Nek9. 相似文献