► Eighty-four compounds were identified in the Tunisian Nigella sativa essential oil. ► The essential oil showed pronounced dose dependant antibacterial activity. ► Thymoquinone cytotoxicity on Hep-2 ...cells was significantly stronger than the essential oil. ► N. sativa essential oil is a good source of bioactive compounds.
We investigate in this work the chemical composition by GC–EIMS, the antibacterial and the cytotoxic activities of Tunisian Nigella sativa essential oil and its bioactive compound, thymoquinone, were tested against various clinical cariogenic bacteria (n=30). Eighty-four compounds were identified in the essential oil. The major one was p-cymene (49.48%) whereas thymoquinone represented only 0.79%. The essential oil (2.43mg/disc) containing only 3.35μg of thymoquinone showed pronounced dose dependant antibacterial activity against Streptococcus mitis, Streptococcus mutans, Streptococcus constellatus and Gemella haemolysans (15.5±0.707mm). However, pure thymoquinone compound (150μg/disk) was active against all the studied strains especially S. mutans and S. mitis (24.5±0.71 and 22±1.41mm inhibition zones, respectively).
Their MIC values are representatives of a good effect. So, the essential oil strongest activity was seen against S. mitis, S. mutans, S. constellatus and G. haemolysans (MIC 2.13mg/ml). However, thymoquinone was active against all the studied strains. The most important antibacterial activity was seen against S. constellatus (MIC 4μg/ml). The growth inhibition effects of thymoquinone on human epithelial cell lines (Hep-2) were significantly stronger than the essential oil. The IC50 of thymoquinone and essential oil were 19.25±1.6 and 55.2±2.1μg/ml, respectively.
Our results demonstrate an important anticariogenic activity of the Tunisian N. sativa essential oil and thymoquinone. These effects further validate the traditional use of N. sativa in the folk medicine against various bacterial infections.
Associations between IKZF1 gene variants and Acute Lymphoblastic Leukemia (ALL) was recently reported. We examined whether the common IKZF1 polymorphisms rs4132601 T/G and rs111978267 A/G are ...associated with ALL among a Tunisian pediatric cohort.
This case-control study involved 170 patients with ALL and 150 control subjects. SNP genotyping was performed by TaqMan® SNP Genotyping Assay.
The minor allele G of IKZF1 gene polymorphism rs4132601 T/G was significantly higher in ALL cases than in control subjects (P = 0.029), with 1.54-fold increased risk of ALL. The association of rs4132601 with ALL was seen under co-dominant (P = 0.009), recessive (P = 0.006), and additive (P = 0.027) genetic models, of which the co-dominant (P = 0.027) and recessive (P = 0.027) association remained significant after adjusting for covariates, and False Discovery Rate correction. In contrast, no association was noted for rs111978267 variant. Two-locus (rs4132601-rs11978267) IKZF1 haplotype analysis demonstrated association of GA (P = 0.053), with increased ALL risk OR (95% CI) = 1.58 (1.00-2.51), which remained significant after controlling for key covariates aP = 0.046; aOR (95% CI) = 1.61 (1.01-2.57).
We demonstrated the association of IKZF1 polymorphism rs4132601 T/G with increased risk of ALL among Tunisian pediatric cohort, with altered phenotypic changes among ALL patients.
Abstract We evaluated pre- and post-thymoquinone (TQ) treatment on 1,2-dimethyl-hydrazine (DMH)-induced oxidative stress during initiation and promotion of colon carcinogenesis. Wistar rats were ...induced with DMH (20 mg/kg) for 10 or 20 weeks, and treated with TQ (5 mg/kg). Following sacrifice, the colons were analysed for tumour development, reactive oxygen species (ROS) generation, lipid peroxidation conjugated diene (CD) and malondialdehyde (MDA), antioxidants glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD) and reduced glutathione (GSH), and histological changes. Increased ROS levels and lipid peroxidation were seen during tumour initiation and promotion. All ROS-scavenging enzyme activities were increased upon shorter DMH treatment but not following longer treatment, while GSH amount was increased upon both treatments. Oxidative state perturbations were associated with moderate colon dysplasia and 30% tumour incidence at initiation and marked dysplasia and 100% tumour incidence at promotion. TQ pre-treatment restored completely DMH-induced oxidative stress at initiation and established histological changes and tumour development. It also abrogated oxidative status aggravation at promotion, and significantly reduced tumour incidence (67%). By comparison, TQ post-treatment corrected oxidative status and attenuated tumour development at initiation. It slightly reduced MDA and antioxidant level at promotion, with a slight reduction in tumour state and dysplasia degree. TQ is efficacious in protecting and curing DMH-induced initiation phase of colon cancer, while exerting a protective role at promotion. TQ effect seems to be related to its capacity in preventing DMH-induced oxidative stress. These in vivo results support the notion that TQ may be of value as a chemo-preventive alternative in colorectal cancer patients.
Polycystic ovary syndrome (PCOS) is characterized by the growth of a number of small cysts on the ovaries which leads to sex hormonal imbalance. Women who are affected by this syndrome suffer from ...irregular menstrual cycles, decline in their fertility, excessive hair growth, obesity, acne and most importantly cardiac function problems. The vascular endothelial growth factor (VEGF) plays a pivotal role in tissue vascularization in general and in the pathogenesis of many diseases. The PCOS was found to be associated with high expression levels of VEGF. In women who undergo assisted reproductive procedures (ART), VEGF was found to be a key mediator of other factors to control ovary angiogenesis. Here, we set out to examine the association of VEGFA gene polymorphism with PCOS and its components in a population of Tunisia women to enhance our understanding of the genetic background leading angiogenesis and vascularization abnormalities in PCOS.
The association of VEGFA gene with PCOS and its components was examined in a cohort of 268 women from Tunisia involving 118 PCOS patients and 150 controls. VEGFA gene variations were assessed through the analysis of the following SNPs rs699947 (A/C), rs833061 (C/T), rs1570360 (G/A), rs833068 (G/A), rs3025020 (C/T), and rs3025039 (C/T). The linkage disequilibrium between SNPs was assessed using HAPLOVIEW software while combination of SNPs into haplotypes in the population and the reconstruction of the cladogram were carried-out by PHASE and ARLEQUIN programs, respectively. Genetic association and genotype-phenotype correlations were calculated by logistic regression and non-parametric tests (Kruskall-Wallis and Mann-Whitney tests), respectively, using StatView program.
We observed 10 haplotypes in our studied cohort whereH1 (ACGG), H2 (ACAG), H7 (CTGG) and H8 (CTGA) were the most frequent. We observed the association of the genotype CT of the SNP rs30225039 with PCOS phenotype (P = 0.03; OR 95 % CI = 2.05 1.07-3.90) and a trend for correlation of the pair of haplotypes H2/H2 with prolactin levels in plasma (P = 0.077; 193.5 ± 94.3 vs 45.7 ± 7.2). These data are consistent with literature and highlight one more time the role of vascularization in the pathogeny of PCOS.
LD pattern in VEGF locus showed a similar LD pattern between the Tunisian population and the CEU. More haplotypes in the Tunisian population than in CEU was observed (22 haplotypes vs 16 haplotypes) suggesting higher recombination rate in Tunisians. The study showed that there was any advantage of using haplotypes compared with SNPs taken alone.
Insofar as altered estrogen receptor-progesterone receptor (PR) expression contribute to breast cancer pathogenesis, previous studies examined the association of genetic variation in PR gene (
PGR
) ...with breast cancer, but with mixed outcome. We evaluated the association between
PGR
variants, and breast cancer and associated features. A retrospective case-control study involving 183 female breast cancer patients, and 222 control women.
PGR
genotyping was done by real-time PCR. Minor allele frequencies of rs1042838, rs590688, and rs10895068
PGR
gene polymorphisms were significantly higher in breast cancer patients compared to controls. Patients carrying rs1042838 G/T, rs590688 C/C, and rs10895068 G/A genotypes had higher risk of breast cancer, while carriage of rs3740753 G/G genotype was associated with marginal reduction in breast cancer risk. In addition, carriage of rs1042839, rs3740753, and rs10895068 minor allele was associated with Her2 status, while rs3740753 and rs10895068 were associated with effective hormone replacement therapy. Furthermore, carriage of rs10895068 minor allele in breast cancer women were also associated with age at first pregnancy, hormone receptor (RH) status, and previous use of oral contraceptives.
PGR
haploview analysis documented moderate-strong linkage disequilibrium (non-random association of alleles at different loci) between 7 of the 8 tested
PGR
SNPs, thus allowing construction of 7-locus
PGR
haplotypes. Two haplotypes, ATG
C
CGA and
G
TG
C
CGA, both containing rs590688, were positively associated with breast cancer, thus assigning a breast cancer-susceptible nature to these haplotypes.
PGR
rs1042838, rs590688, and rs10895068, and ATGCCGA and
G
TG
C
CGA haplotypes are related with increased breast cancer susceptibility in Tunisian women.
The abnormal production of matrix metalloproteinases (MMPs), especially MMP-9 and MMP-2, plays a pivotal role in hypertensive disorders of pregnancy, and as such, can influence the development of ...preeclampsia. These alterations may result from functional genetic polymorphisms in the promoter region of MMP-9 and MMP-2 genes, which modify MMP-9 and MMP-2 expression. We investigated the association of MMP-9 polymorphism rs3918242 (-1562 C>T) and MMP-2 polymorphism rs2285053 (-735 C>T) with the risk of preeclampsia. This case–control study was conducted on 345 women with preeclampsia and 281 age-matched women with normal pregnancies from Tunisian hospitals. Genomic DNA was extracted from whole blood collected at delivery. Genotypes for -1562 C>T and -735 C>T polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). An increased frequency of heterozygous MMP-9 -1562 C/T genotype carriers was observed in women with preeclampsia compared to healthy controls (p = 0.03). In contrast, the MMP-2 -735 C>T polymorphism was not significantly different regarding frequency distribution of the allele and genotype between healthy pregnant women and women with preeclampsia. Our study suggests that the MMP-9 -1562 C/T variant, associated with high MMP-9 production, could be a genetic risk factor for preeclampsia in Tunisian women.
Background:
Preeclampsia (PE) is a pregnancy-associated hypertensive disorder and a leading cause of maternal and neonatal morbidity and mortality. While its pathogenesis remains ill defined, several ...candidate genes for PE have been identified, but results remain inconclusive. We investigated the association of the angiotensinogen (AGT) gene variants M235T and T174M with PE, and we analyzed the contribution of both variants to the severity of PE.
Methods:
This case-control study enrolled 550 Tunisian pregnant women: 272 with PE, of whom 147 presented with mild, and 125 with severe PE, along with 278 unrelated age- and ethnically matched control women. AGT genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism.
Results:
Significantly higher M235T minor allele frequency (MAF) was associated with increased risk of PE (p < 0.001). Decreased frequency of heterozygous T174M genotype carriers were found in control women (p = 0.015), suggesting a protective effect of this genotype (odds ratio (95% confidence interval) = 0.51 (0.29–0.89)). Two-locus haplotype analysis demonstrated MM and TT haplotypes to be negatively and positively associated with PE, respectively. MAF of M253T, but not T174M, was higher in the severe PE group, and carrying M235T or T174M minor allele was associated with increased body mass index (p < 0.001) among unselected PE women.
Conclusions:
AGT M235T and T174M variants contribute to an increased risk of developing PE, and for M235T to PE severity.
Abstract Point mutations in methylenetetrahydrofolate reductase (MTHFR) and hyperhomocysteinemia were implicated in the pathogenesis of diabetic nephropathy (DN) in many ethnic groups. This study ...addressed the association of C677T and A1298C single nucleotide polymorphisms (SNPs) of MTHFR gene with DN in Tunisian type 2 diabetes (T2DM) patients. Study subjects comprised 93 DN patients, 267 patients with normoalbuminuria, and 400 control subjects. C677 T and A1298 C genotypes were determined by PCR-RFLP analysis, and homocysteine levels were measured by ELISA. A1298 C and C677 T were highly prevalent among T2DM patients, with allele frequencies of 0.26 and 0.36, respectively. Higher mutant 677 T allele and 677C/ T and 677 T / T genotypes of C677 T SNP, but not A1298 C SNP, together with 677C/1298A, 677C/1298 C , and 677 T /1298A haplotypes were seen in DN patients compared to normoalbuminuric patients, ( p < 0.001). Plasma homocysteine was positively associated with MTHFR 677 T / T genotype among the three groups, and was significantly elevated in double heterozygous DN patients but not in normoalbuminuric patients or controls. Logistic regression analysis with DN as dependent variable showed that homocysteine (OR, 1.153) and MTHFR 677 T / T (OR, 9.799) were the only variables associated with DN, after adjusting for possible confounding variables. C677 T , but not A1298 C , SNP, is a risk factor for DN, presumably acting by elevating homocysteine levels.
The effect of thymoquinone (TQ), the abundant component of black cumin seed (Nigella sativa) oil extract, was evaluated on 1,2-dimethylhydrazine (DMH)-induced erythrocyte oxidative stress and ...haematological perturbations during colon cancer promotion in rats. Two TQ approaches, the pre- and post-treatment, were used. DMH promoted erythrocyte oxidative damage in rats by enhancing lipid peroxidation (30%) and decreasing antioxidant enzymes activities (20–35%). This was associated with the decline of erythrocyte count, haemoglobin concentration and haematocrit (20%) and the count increase of white blood cell (60%) and platelet (180%). TQ pre-treatment repaired DMH-induced erythrocyte oxidative stress, anaemia, leukocytosis, and thrombocytosis and allowed a 60% of tumour incidence decline. TQ post-treatment exerted a slight effect on erythrocyte oxidative stress and reduced colon cancer incidence by 30% only. Thus, TQ efficacy in preventing DMH-induced colon cancer promotion was related to its virtue antioxidant effect on erythrocyte oxidative stress.
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