Efficacy of Essential Oils on Fungi Isolated from Archaeological Objects in Saqqara Excavation,Egypt

The archeological objects constitute an important part of the worldwide cultural heritage. The impact of the fungal activity on the deterioration of cultural heritage is a global problem and their preservation over time is a challenging task. Antifungal activities of 12 essential oils (EOs) (black cumin, castor, cinnamon, clove, cumin, garlic, geranium, lavender, lemongrass, menthe, olive, and thyme) were examined against 16 fungal species isolated from three tested archaeological objects (wall painting stone, wooden statue, and pottery coffin) from Saqqara stores in Egypt. Molecular identification was carried out for the highly frequent species (Aspergillus niger, A. flavus and Rhizopus oryzae) in the three tested archaeological samples. Antifungal activity and minimal inhibitory concentration (MIC) of the tested EOs with different concentrations (0.125, 0.25, 0.5, 0.75, 1?μl/ml) were measured.

The most efficient EOs were thyme (MIC ranged from 0.25–0.75μl/ml) followed by clove (MIC ranged from 0.25–1?μl/ml) and geranium, (MIC ranged from 0.5–1?μl/ml). Thymol (37.1%) and p-Cymene (26.32%) were the active constituents of thyme, while Triacetin (69.36%) and eugenol (28.67) were the most efficient components of clove oil followed by geranium active components (à-Citronellol 20.62% and Geraniol 14.43%). Aspergillus niger was the most resistance species, while Fusarium oxysporum and Penicilium citrinium were the most susceptible ones.     

CCR5 Is a Therapeutic Target for Recovery after Stroke and Traumatic Brain Injury

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The convenient use of fluorescamine for spectrofluorimetric determination of midodrine hydrochloride in pure form and its tablets formulation: Application to content uniformity testing

A novel sensitive and simple spectrofluorimetric method was developed then validated for determination of midodrine in both its authentic pure form and its tablets. This method is based on the reaction between midodrine's aliphatic primary amine moiety with fluorescamine reagent, using borate buffer at pH 7.8 and yielding a highly fluorescent product whose fluorescence intensity was measured at 462 nm after excitation at 388 nm. This method represents the first attempt for determination of midodrine spectrofluorimetrically. A calibration curve was constructed showing that the linear range was 0.2–3.0 μg/ml. The limit of detection and limit of quantitation values were 0.06 and 0.19 μg/ml respectively. The correlation coefficient (r) and the determination coefficient (r²) values were 0.9992 and 0.9984 respectively. The proposed method was validated according to ICH guidelines and successfully applied for determination of midodrine in its tablets with an overall % recovery of 99.56 ± 0.95. Finally, the presented method was adapted to study the content uniformity test according to United States Pharmacopeia guidelines.     

LLY-507, a Cell-active,Potent, and Selective Inhibitor of Protein-lysine Methyltransferase SMYD2

SMYD2 is a lysine methyltransferase that catalyzes the monomethylation of several protein substrates including p53. SMYD2 is overexpressed in a significant percentage of esophageal squamous primary carcinomas, and that overexpression correlates with poor patient survival. However, the mechanism(s) by which SMYD2 promotes oncogenesis is not understood. A small molecule probe for SMYD2 would allow for the pharmacological dissection of this biology. In this report, we disclose LLY-507, a cell-active, potent small molecule inhibitor of SMYD2. LLY-507 is >100-fold selective for SMYD2 over a broad range of methyltransferase and non-methyltransferase targets. A 1.63-Å resolution crystal structure of SMYD2 in complex with LLY-507 shows the inhibitor binding in the substrate peptide binding pocket. LLY-507 is active in cells as measured by reduction of SMYD2-induced monomethylation of p53 Lys³⁷⁰ at submicromolar concentrations. We used LLY-507 to further test other potential roles of SMYD2. Mass spectrometry-based proteomics showed that cellular global histone methylation levels were not significantly affected by SMYD2 inhibition with LLY-507, and subcellular fractionation studies indicate that SMYD2 is primarily cytoplasmic, suggesting that SMYD2 targets a very small subset of histones at specific chromatin loci and/or non-histone substrates. Breast and liver cancers were identified through in silico data mining as tumor types that display amplification and/or overexpression of SMYD2. LLY-507 inhibited the proliferation of several esophageal, liver, and breast cancer cell lines in a dose-dependent manner. These findings suggest that LLY-507 serves as a valuable chemical probe to aid in the dissection of SMYD2 function in cancer and other biological processes.     

Associations between Apolipoprotein E Genotype, Diet, Body Mass Index, and Serum Lipids in Lithuanian Adult Population

Background

Apolipoprotein E (APOE) polymorphism is associated with lipid levels. Some studies have reported that blood lipid response to diet or obesity varies depending on APOE genotypes. The aim of this study was to assess the effect of APOE genotypes, the intake of saturated fatty acids (SFA), and obesity on serum lipid levels in Lithuanian adult population.

Methodology/Principal Findings

A cross-sectional health survey was carried out in five municipalities of Lithuania. The random sample was obtained from lists of 25–64 year-old inhabitants registered at primary health care centres. The data from 996 subjects (416 men and 580 women) were analysed in this study. Two single-nucleotide polymorphisms (rs429358 and rs7412) were assessed using a real-time polymerase chain reaction. 24-hour recall and food frequency questionnaire were used for evaluation of dietary habits. Serum lipids were determined using enzymatic methods.Men and women with the APOE2 genotype had the lowest level of total cholesterol (TC) (p = 0.002 for men, and p = 0.02 for women) and low-density lipoprotein cholesterol (LDL-C) (p<0.001). Multivariate linear regression analysis showed that age, genotype APOE2, SFA intake, and body mass index (BMI) were significant determinants of TC and LDL-C level (with p values ranging from 0.043 to 0.001). Our data did not reveal any statistically significant interactions between APOE genotype and SFA intake or between APOE genotype and BMI regarding TC and LDL-C level (all p>0.05). However, the predictive power of the regression model for LDL-C improved when gene-BMI interaction and gene-BMI interaction plus gene-nutrient interaction were added (p = 0.04 and p = 0.032 for R² change, respectively).

Conclusions/Significance

APOE genotypes, SFA intake, and obesity were found to be associated with blood lipid levels in Lithuanian adult population. Analysis of gene-diet and gene-obesity interactions did not confirm that the effects of diet and obesity on TC and LDL-C level significantly depended on APOE genotype.     

p53 Codon 72 arginine/proline polymorphism and cancer in Sudan

The aim of this report is to determine frequencies and associations of p53 codon 72 arg/pro polymorphism with different types of cancer in Sudan. p53 codon72 arg/pro polymorphism distribution and allele frequencies in 264 samples of different types of cancers were investigated using PCR. The results were compared to 235 normal controls. The results indicated significant differences in frequency and genotype association between different types of cancers. Breast carcinoma patients most prominently showed excess of homozygous arg genotype as compared to controls with an Odd ratio (OR) of 19.44, 95?%CI: 6.6–78.3, P?<?0.0001. Less prominently cervical cancer showed genotype effect of 2.4 OR, 95?%CI: 1.12–5.33, P?=?0.015, while esophageal cancer had an OR of 0.57, 95?%CI: 0.23–1.42, P?=?0.1. In Burkitt’s lymphoma, however, in contrast the homozygous arg accounted for only 6.9?%, (OR 0.18, 95?%CI: 0.02–0.89, P?=?0.018). We concluded that p53 arg/pro polymorphism has different pattern of frequency in different types of cancer among Sudanese patients, indicating perhaps different etiology and biology of these tumours.     

Histone recognition and large-scale structural analysis of the human bromodomain family

Bromodomains (BRDs) are protein interaction modules that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. The 61 BRDs in the human genome cluster into eight families based on structure/sequence similarity. Here, we present 29 high-resolution crystal structures, covering all BRD families. Comprehensive crossfamily structural analysis identifies conserved and family-specific structural features that are necessary for specific acetylation-dependent substrate recognition. Screening of?more than 30 representative BRDs against systematic histone-peptide arrays identifies new BRD substrates and reveals a strong influence of flanking posttranslational modifications, such as acetylation and phosphorylation, suggesting that BRDs recognize combinations of marks rather than singly acetylated sequences. We further uncovered a structural mechanism for the simultaneous binding and recognition of diverse diacetyl-containing peptides by BRD4. These data provide a foundation for structure-based drug design of specific inhibitors for this emerging target family.     

Trends in prevalence, awareness, treatment, and control of hypertension, and the risk of mortality among middle-aged Lithuanian urban population in 1983-2009

ABSTRACT: BACKGROUND: Arterial hypertension (AH) is a main risk factor for the risk from cardiovascular (CVD) and stroke mortality. Only few data was published on prevalence, awareness and management of AH in Lithuania. Development of objective approaches to the treatment and control of AH reduces the risk of mortality. The aim of this study was to evaluate time trends, the prevalence, awareness, treatment and control of AH and risk of mortality among Lithuanian urban population aged 45--64 years during the period of 1983--2009. METHODS: Time trends of AH and risk of mortality were examined in three MONICA health surveys in 1983, 1986, 1992, and in one health survey according to MONICA protocol in 2002 included randomly recruited of 2,218 men and 2,491 women. AH was defined as systolic blood pressure (BP) [GREATER-THAN OR EQUAL TO]140 mmHg and/or diastolic BP of [GREATER-THAN OR EQUAL TO]90 mmHg or current use of antihypertensive medication. The main outcome measures were all-cause mortality, mortality from CVD, coronary heart disease (CHD) and stroke. The mean duration of follow-up was 11.8 [PLUS-MINUS SIGN] 9.2 years. All survey periods were age standardized to the year 2006 of Kaunas population. The estimates of hazard ratio and 95% confidence interval were based on the multivariate Cox proportional hazards regression. RESULTS: In men during 1983--2002 period hypertension prevalence was 52.1--58.7% and did not significantly change whereas in women decreased from 61.0 to 51.0%. There was a significant increase in hypertension awareness among hypertensive men and women (45.0 to 64.4% and 47.7 to 72.3%, respectively) and in treated hypertensives (55.4 to 68.3% in men and 65.6 to 86.2% in women). Adjusted Cox proportional hazard regression analyses revealed a strong dose--response association between blood-pressure level and all-cause, CVD, CHD and stroke-mortality risk in both men and women groups. CONCLUSION: In Lithuanian urban population the prevalence of hypertension remains high. Despite positive changes in hypertension awareness and treatment, hypertension control remains poor. A strong dose--response association between the level of BP and all-cause, CVD, CHD and stroke mortality risk was indicated.     

Educational inequalities in cancer incidence and mortality in Lithuania: A record linkage study

BackgroundThe aim of this study is to describe associations between incidence and mortality by major cancer sites and education in Lithuania.MethodsThe study is based on the linkage between all records of the 2001 population census and all records from Lithuanian Cancer Registry (cancer incidence) and Statistics Lithuania (deaths) for the period between 1 July 2001 and 31 December 2004. Education-specific incidence and mortality rate ratios were estimated by means of multivariate Poisson regression models.ResultsWe found both the positive and inverse educational gradients in cancer incidence and mortality. The risk of developing cancer (all sites) was lower among men and women with the lowest education, whereas cancer mortality was higher among lower educated men. The higher educational level was also associated with an increased risk of prostate cancer among men and an increased risk of breast cancer among women. However, prostate cancer mortality was the highest in the lowest education group, whereas breast cancer mortality among women did not show any statistically significant differences. Lower educated men had significantly higher incidence and mortality due to lung and stomach cancers. Strikingly high incidence and mortality due to cervix cancer was observed among women with secondary and lower than secondary education.ConclusionThe results point to inequalities in early diagnosis and survival from cancer and failures ensuring equal access to medical care. Further more in-depth studies are needed in order to understand the nature and determinants of these inequalities.