BackgroundA major concern of cancer chemotherapy is the side effects caused by the non-specific targeting of both normal and cancerous cells by therapeutic drugs. Much emphasis has been placed on discovering new compounds that target tumour cells more efficiently and selectively with minimal toxic effects on normal cells.Methodology/Principal FindingsThe cytotoxic effect of thymoquinone, a component derived from the plant Nigella sativa, was tested on human glioblastoma and normal cells. Our findings demonstrated that glioblastoma cells were more sensitive to thymoquinone-induced antiproliferative effects. Thymoquinone induced DNA damage, cell cycle arrest and apoptosis in the glioblastoma cells. It was also observed that thymoquinone facilitated telomere attrition by inhibiting the activity of telomerase. In addition to these, we investigated the role of DNA-PKcs on thymoquinone mediated changes in telomere length. Telomeres in glioblastoma cells with DNA-PKcs were more sensitive to thymoquinone mediated effects as compared to those cells deficient in DNA-PKcs.Conclusions/SignificanceOur results indicate that thymoquinone induces DNA damage, telomere attrition by inhibiting telomerase and cell death in glioblastoma cells. Telomere shortening was found to be dependent on the status of DNA-PKcs. Collectively, these data suggest that thymoquinone could be useful as a potential chemotherapeutic agent in the management for brain tumours.

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BACKGROUNDThe estimated prevalence of nonalcoholic fatty liver disease (NAFLD) in Saudi Arabia is 7% to 10%. Despite the high prevalence of risk factors including diabetes, obesity, and hyperlipidemia, no recent epidemiological studies have measured the disease burden. We aimed to determine the characteristics of Saudi NAFLD patients attending a university hospital, and study factors affecting alanine aminotransferase (ALT) levels.DESIGN AND SETTINGA prospective study among patients referred for ultrasonography in King Khalid University Hospital in Riyadh, Saudi Arabia from February to May 2009.PATIENTS AND METHODSNAFLD was defined as an appearance of fatty liver on routine abdominal ultrasound in the absence of coexisting liver disease and alcohol consumption. Patients were classified into normal and high ALT (ALT >60 U/L) level groups for analysis.RESULTSThe prevalence of NAFLD was 16.6% (218/1312). Patients with normal ALT had the mean (SD) age of 45.9 (10.6) years and the mean body mass index of 34.5 (7.9) kg/m2. Forty percent of the 151 patients with normal ALT had diabetes, 66.2% were obese, and 29.1% had hypertension. Forty-three patients (23%) had high ALT levels. These patients had significantly lower age (P=.003) and fasting blood sugar (P=.03) than the normal ALT group. Non-diabetic patients (odds ratio 0.30, 95% CI 0.1–0.8), men (female OR 0.23, 95% CI 0.1–0.5), lower cholesterol (P=.001), high-density lipoprotein (P=.006), and low-density lipoprotein (P=.008) levels were more likely to be observed among patients with high ALT levels. In a multivariate analysis, younger age (OR 0.96, 95% CI 0.93–0.99), being male (OR 0.23, 95% CI 0.09–0.57), and a lower cholesterol level (OR 0.55, 95% CI 0.37–0.82) were significant predictors of high ALT levels.CONCLUSIONBased on the high prevalence of obesity and diabetes, the prevalence of NAFLD will continue to be high, unless awareness is inculcated among the local population.

Inflammation appears to be important in lung carcinogenesis among smokers, but its role among never-smokers is not well established. We hypothesized that inflammatory medical conditions and gene polymorphisms interact to increase lung cancer risk in never-smokers. We interviewed 433 Singaporean female never-smoker lung cancer patients and 1375 hospital controls, and evaluated six polymorphisms in the interleukin 1-β, interleukin 6 (IL6), cyclooxygenase-2, peroxisome proliferator-activated receptor-γ and interleukin 1-β receptor antagonist (IL1RN) genes. Tuberculosis was associated with a non-significant elevated risk of lung cancer [odds ratio (OR) 1.58, 95% confidence interval (CI) 0.95-2.62]. There was no effect of asthma, atopy or chronic productive cough individually. However, the presence of one or more of these conditions (asthma, cough or atopy) increased risk (OR 2.24, 95%CI 1.15-4.38) in individuals possessing the T/T genotype at interleukin 1-β -31T/C, but not in those possessing the C/T (OR 0.87, 95%CI 0.51-1.57) or C/C genotypes (OR 0.58, 95%CI 0.27-1.27), and in individuals having the *2 variable number of tandem repeat allele of IL1RN [OR 5.09 (1.39-18.67)], but not in those without (OR 0.93, 95%CI 0.63-1.35). The IL6-634 G allele increased the risk of lung cancer (OR 1.44, 95%CI 1.07-1.94). Lung cancer risk also increased with the number of polymorphism sites where at least 1 'risk' allele was present [interleukin 1-β -31T/C (T allele), IL1RN (*2 allele) and IL6-634C/G (G allele)] among those with asthma, cough or atopy (Ptrend 0.001) but not in those without (Ptrend 0.47). Our results suggest that the effect of inflammatory medical conditions on lung cancer in never-smokers is modulated by host genetic susceptibility and will need to be confirmed in other studies conducted in similar populations.

Objectives: Lead and homocysteine are both linked to cardiovascular disease. With this in mind, the authors evaluated the relation between blood lead and homocysteine in people aged 19-66 years in two Asian populations. Methods: This cross-sectional study comprised 183 workers from a lead stabiliser factory in Singapore and 323 workers from a battery factory in Vietnam. Workers were occupationally exposed to lead. Blood lead was analysed using atomic absorption spectrophotometry while plasma homocysteine was measured using high performance liquid chromatography. Results: Chinese subjects had the lowest blood lead levels while the Indians had the highest. Controlling for age, sex and race, an increase of 1 mg/dl in blood lead was associated with an increase of 0.04 mmol/l of homocysteine on the log scale. Gender and ethnicity seemed to be strongly associated with the relation between lead and homocysteine. The positive relation between lead and homocysteine among the Vietnamese subjects was significant (Pearson's r = 0.254, p,0.01). When blood lead levels were divided by quartiles, the correlation coefficient between blood lead levels in the 4th quartile and homocysteine among the Vietnamese was higher (r = 0.405, p,0.01). Overall, an increase of 1 mg/dl in blood lead in all the Vietnamese subjects was associated with an increase of 0.05 mmol/l increase in homocysteine on the log scale. However, in the 4th quartile, the same increase was associated with an increase of 0.41 mmol/l of homocysteine on the log scale. Conclusions: Blood lead was found to be associated with homocysteine levels in this Asian sample. Although we cannot determine causality from cross-sectional data, it is sensible to consider the probability that this relation could explain one of the mechanisms of the impact of lead on the cardiovascular system. More studies would be needed to confirm this inference.

BackgroundGenome-wide association studies have recently revealed that several single-nucleotide polymorphisms (SNPs) in the interleukin (IL) 28B genes can predict the sustained virological response (SVR) to pegylated interferon-α2a/b plus ribavirin in hepatitis C virus (HCV)-genotype 1 patients. However, data for patients infected with HCV genotype 4 (HCV-G4) are limited.AimWe analyzed the association of IL28B SNPs (hematological, biochemical, virological, and pathological factors) with SVR in the HCV-G4 monoinfected cohort of patients.Patients and methodsOne hundred twenty-nine treatment-naïve HCV-G4 patients undergoing treatment were recruited from three tertiary care centers in Saudi Arabia. Five IL28B SNPs (rs12979860, rs12980275, rs8105790, rs8099917, and rs72486680) were identified by polymerase chain reaction and DNA sequencing. SVR was statistically correlated with various clinical, histopathological, virological, and genetic parameters.ResultsSVR was significantly associated with the CC and AA alleles of rs12979860 (p = 0.008) and rs12980275 (p = 0.004), respectively. Moreover, albumin levels (p = 0.002) and platelet count (p = 0.039) showed significant differences in the SVR and No SVR groups. On multivariate analysis, the CC allele of rs12979860 (OR, 2.89; 95 % CI 1.6–6.2, p = 0.006) and albumin levels (OR, 1.2; 95 % CI 1.1–1.4, p = 0.001) independently predicted SVR.ConclusionsIL28B polymorphism (CC allele of rs12979860) predicts the sustained response to antiviral therapy in HCV-G4.Electronic supplementary materialThe online version of this article (doi:10.1007/s12072-013-9421-8) contains supplementary material, which is available to authorized users.

With reference to the newly released microgrid standards, design and real-time implementation of a centralized microgrid control system is presented in this article. In the grid-connected mode, the utility grid will provide the voltage and frequency reference at the point of connection. The assets within the microgrid will follow power command references provided by the control system. In the islanded mode, the energy storage system (ESS) can provide the voltage and frequency reference to all other generators. Based on the state-of-charge of the ESS, a rule-based dispatch is proposed, with priority given to diesel generator and then the storage in the middle state of charge range. To alleviate power fluctuations, meet smooth planned islanding requirement, and compensate for the feeder losses ignored in dispatch algorithm, a supplementary slackbus power control based on closed-loop feedback and first-order filter is proposed. The potential of the storage system in firming short-time power fluctuation and providing long-term load shifting capabilities is exploited. An emergency dispatch function for unplanned islanding considering the speed of response limitation of a diesel generator is also proposed. The proposed control strategy is implemented and tested on a controller hardware-in-the-loop test bench. It demonstrates the capability of the control system to reduce load shedding and renewable curtailment, and to implement power management at the point of interconnection. Index Terms-Controller hardware-in-the-loop (C-HIL) test, microgrid control system (MGCS), rule-based dispatch, slackbus power control, smooth transition, state of charge (SoC) management.

The ULN for ALT levels in Middle Eastern populations should be lowered, including separate values for males and females. Furthermore, metabolic parameters were shown to have a significant effect on ALT levels.