Contribution of ABCG2 gene polymorphisms (G34A and C376T) in the prognosis of colorectal cancer

73-78This study aims to assess the association of two single nucleotide polymorphisms (SNPs), G34A and C376T, in the ABCG2 gene with the risk of developing CRC. To the best of our knowledge, this is the first study that determined the role of genetic variations in the ABCG2 gene with the risk of CRC in Saudi Arabia. The gDNA was extracted from the blood of 58 CRC patients and 48 healthy subjects. The DNA sequencing was used to determine the distribution of genotypes. The results showed that CRC patients carried a heterozygous (GA) genotype for SNP G34A had a low risk of developing CRC (odds ratio=0.015, 95% CI [0.00–0.12]; risk ratio=0.35, 95% CI [0.25–0.12], P P 0.0001). In conclusion, the results indicated that a heterozygous (GA) genotype in SNP G34A may decrease the risk of CRC development, whereas, the heterozygous (CT) genotype in SNP C376T may increase the risk of CRC. The results may suggest a protective role of ABCG2 SNP G34A against CRC and a deleterious effect of ABCG2 SNP C376T for increasing the risk of CRC

An Investigation of the Neurotoxic Effects of Malathion, Chlorpyrifos, and Paraquat to Different Brain Regions

Acute or chronic exposures to pesticides have been linked to neurotoxicity and the potential development of neurodegenerative diseases (NDDs). This study aimed to consider the neurotoxicity of three widely utilized pesticides: malathion, chlorpyrifos, and paraquat within the hippocampus (HC), corpus striatum (CS), cerebellum (CER), and cerebral cortex (CC). Neurotoxicity was evaluated at relatively low, medium, and high pesticide dosages. All pesticides inhibited acetylcholinesterase (AChE) and neuropathy target esterase (NTE) in each of the brain regions, but esterase inhibition was greatest in the HC and CS. Each of the pesticides also induced greater disruption to cellular bioenergetics within the HC and CS, and this was monitored via inhibition of mitochondrial complex enzymes I and II, reduced ATP levels, and increased lactate production. Similarly, the HC and CS were more vulnerable to redox stress, with greater inhibition of the antioxidant enzymes catalase and superoxide dismutase and increased lipid peroxidation. All pesticides induced the production of nuclear Nrf2 in a dose-dependent manner. Collectively, these results show that pesticides disrupt cellular bioenergetics and that the HC and CS are more susceptible to pesticide effects than the CER and CC

Comparative Study of the Antioxidant Activity of Two Popular Green Tea Beverages Available in the Local Market of Saudi Arabia

Abstract Antioxidants have numerous applications due to their multiple roles in diminishing harmful effects of oxidative stress. The objective of this work was to highlight the importance of green tea by evaluating the antioxidant activity of the most popular green tea brands in Saudi Arabia, Lipton and Rabea. To our knowledge, no studies have so far been done to estimate the antioxidant activity of these brands. To determine the antioxidant activities of these two brands, 10 mg/ml of each brand was extracted and their total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, hydrogen peroxide scavenging activity, ferric reducing power and ferrous ion chelating effect were measured. The TPC of Lipton tea was 678.7 µg of gallic acid equivalents (GAE)/10mg, whereas in Rabea tea, the TPC was 647.1 µg GAE/10mg. The presence study indicated that there were no significant differences in total phenolic contents and the percentage inhibition as shown in DPPH and H 2 O 2 assays among Lipton and Rabea green teas. Moreover, it was found that all assays have exhibited high antioxidant activity in both green teas. In conclusion, our study showed evidence for evenness and stability of the antioxidant activity of the two commercial green teas available in the markets of Saudi Arabia. Continued researches are needed to further the current knowledge on the health-promoting effects of this popular beverage using different supplements by different mechanisms

ABCB1 variants C3435T and T129C are not associated with colorectal cancer risk

Background: Colorectal cancer (CRC) is one of the most prevalent cancers in Saudi Arabia that is highly characterized with poor survival rate and advanced metastasis. Many studies contribute this poor outcome to the expression of ABC transporters on the surface of cancer cells. Objectives: In this study, two ABCB1 variants, C3435T and T129C, were examined to evaluate their contribution to CRC risk. Methods: 125 subjects (62 CRC patients and 63 healthy controls) were involved. The DNA was isolated and analyzed with PCR-RFLP to determine the different genotypes. The hardy-Weinberg equilibrium was performed to determine genotype distribution and allele frequencies. Fisher\u2019s exact test (two-tailed) was used to compare allele frequencies between patients and control subjects. Results: The study showed that for SNP C3435T, the population of both CRC patients and controls were out of Hardy-Weinberg equilibrium. Genotype distribution for CRC patients was (Goodness of fit \u3c72 = 20, df= 1, P 640.05), whereas, for the controls the genotype distribution was (Goodness of fit \u3c72 = 21, df =1, P 640.05). For SNP T129C, all subjects showed normal (TT) genotype. Conclusion: There was no significant association between ABCB1 3435C>T and 129T>C polymorphisms with CRC risk

Differential Effects of Paraquat, Rotenone, and MPTP on Cellular Bioenergetics of Undifferentiated and Differentiated Human Neuroblastoma Cells

Paraquat (PQ), rotenone (RO), and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are neurotoxicants that can damage human health. Exposure to these neurotoxicants has been linked to neurodegeneration, particularly Parkinson’s disease. However, their mechanisms of action have not been fully elucidated, nor has the relative vulnerability of neuronal subtypes to their exposures. To address this, the current study investigated the cytotoxic effects of PQ, RO, and MPTP and their relative effects on cellular bioenergetics and oxidative stress on undifferentiated human neuroblastoma (SH-SY5Y) cells and those differentiated to dopaminergic (DA) or cholinergic (CH) phenotypes. The tested neurotoxicants were all cytotoxic to the three cell phenotypes that correlated with both concentration and exposure duration. At half-maximal effective concentrations (EC50s), there were significant reductions in cellular ATP levels and reduced activity of the mitochondrial complexes I and III, with a parallel increase in lactate production. PQ at 10 µM significantly decreased ATP production and mitochondrial complex III activity only in DA cells. RO was the most potent inhibitor of mitochondrial complex 1 and did not inhibit mitochondrial complex III even at concentrations that induced a 50% loss of cell viability. MPTP was the most potent toxicant in undifferentiated cells. All neurotoxicants significantly increased reactive oxygen species, lipid peroxidation, and nuclear expression of Nrf2, with a corresponding inhibition of the antioxidant enzymes catalase and superoxide dismutase. At a 10 µM exposure to PQ or RO, oxidative stress biomarkers were significant in DA cells. Collectively, this study underscores the importance of mitochondrial dysfunction and oxidative stress in PQ, RO, and MPTP-induced cytotoxicity and that neuronal phenotypes display differential vulnerability to these neurotoxicants

Factors associated with hospital service satisfaction in a sample of Arab subjects with schizophrenia

<p>Abstract</p> <p>Background</p> <p>Assessment of patients' satisfaction with health care services could help to identify the strengths and weaknesses of the system and provide guidance for further development. The study's objectives were to: (i) assess the pattern of satisfaction with hospital care for a sample of people with schizophrenia in Kuwait, using the Verona Service Satisfaction Scale (VSSS-EU); ii) compare the pattern of satisfaction with those of similar studies; and iii) assess the association of VSSS seven domains with a number of variables representing met and unmet needs for care, family caregiver burden, severity of psychopathology, level of psychosocial functioning, socio-demographic characteristics, psychological well-being and objective quality of life.</p> <p>Methods</p> <p>Consecutive outpatients in stable condition and their family caregivers were interviewed with the VSSS-EU and measures of needs for care, caregiver burden, quality of life and psychopathology.</p> <p>Results</p> <p>There were 130 patients (66.1%m, mean age 36.8). While over two-thirds expressed satisfaction with the domains of "overall satisfaction", "professionals' skills", "access", "efficacy", and "relatives' involvement", only about one-third were satisfied with the domains of "information" and "types of intervention". The later two domains were the areas in which European patients had better satisfaction than our patients, while our patients expressed better satisfaction than the Europeans in the domain of "relatives' involvement". In multiple regression analyses, self-esteem, positive and negative affect were the most important correlates of the domains of service satisfaction, while clinical severity, caregiver burden and health unmet needs for care played relatively minor roles.</p> <p>Conclusion</p> <p>The noted differences and similarities with the international data, as well as the predictive power of self-esteem and affective state, support the impression that patients' attitudes towards psychiatric care involve a complex relationship between clinical, personal and socio-cultural characteristics; and that many of the factors that impact on satisfaction with service relate to individual psychological characteristics. The weaknesses in the system, highlighted by the pattern of responses of the participants, indicate possible gaps in the provision of comprehensive psychiatric care in the country and obviate the need for public mental health education and development of services to enhance the quality of care.</p

Correlation of leptin and sex hormones with endocrine changes in healthy Saudi women of different body weights

Background: A relationship between estrogen and leptin has been described during the follicular phase of both spontaneous menstrual cycles and cycles stimulated with exogenous follicle-stimulating hormone (FSH), which suggest that leptin has either a direct effect on or is regulated by gonadal steroids in the human ovary. To examine the changes in plasma leptin levels during the menstrual cycle, we studied the association between plasma leptin and reproductive hormones in young, healthy Saudi women. Subjects and Methods: Sixty-five young women between 19 to 39 years of age, with a normal menstrual cycle, were grouped into 33 overweight and obese females of BMI&#62; 25 kg/m2, and 32 lean females of BMI &#60; 25 kg/m2. Anthropometrics measurements were made at the time of the collection. Samples were analyzed for leptin, progesterone, estradiol (E2), FSH, luteinizing hormone (LH), cortisol, and testosterone concentrations. Results: Overweight and obese women, compared with lean, tended to have a significantly higher plasma leptin levels (11.38&#177; 4.06 vs. 6.22&#177; 2.87 ng/mL; P=0.05). In overweight and obese subjects, circulating leptin concentrations showed a direct correlation with BMI (r=0.53; P=0.002), hip circumference (r=0.32; P=0.005), waist-hip ratio (r=0.37; P=0.042), weight (r=0.41; P=0.021), and E 2 on day 3 (r=0.35; P=0.048). In all correlation analyses, leptin levels did not correlate with cortisol or testosterone. In lean subjects, a bivariate correlation analysis showed that plasma leptin concentrations were directly correlated to hip circumference (r=0.43; P=0.012). Moreover, a direct correlation was found with progesterone on day 10 (r=0.43; P=0.014) and E2 on day 24 (r=0.47; P=0.007). Conclusion: There is a link between plasma leptin and progesterone concentrations during the menstrual cycle, and the variation in circulating estradiol concentrations may have an influence on circulating leptin in female subjects

Genetic Variants in the Mitochondrial Thymidylate Biosynthesis Pathway Increase Colorectal Cancer Risk

We assess the contributions of genetic variants for the enzymes involved in capecitabine metabolism to colorectal cancer (CRC) development risk. In this case-control study, DNA samples were collected from 66 patients (King Abdulaziz University Hospital) and 65 controls (King Fahad General Hospital) between April and November 2022 to be used in PCR-RFLP. The chi-square (χ2) test at a significance level of p ˂ 0.05 was used to estimate genotype and allele frequencies. The Lys27Gln variant of cytidine deaminase (CDA) showed a risk ratio (RR) of 1.47 for heterozygous (AC) carriers, with genotype distributions for patients (χ2 = 1.97) and controls (χ2 = 14.7). Homozygous (AA) Ala70Thr carriers demonstrated a three-fold higher risk, with genotype distributions for patients (χ2 = 3.85) and controls (χ2 = 4.23). Genotype distributions of the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T variant for patients were (χ2 = 22.43) and for controls were (χ2 = 0.07); for the MTHFR A1298C variant, they were (χ2 = 54.44) for patients and (χ2 = 4.58) for controls. Heterozygous (AC) carriers of the A1298C variant demonstrated highly significant protection against CRC development (RR = 0.2, p = 0.001), while a two-fold higher risk for CRC was estimated for homozygous genotype (CC) carriers. In conclusion, the heterozygous genotype of CDA Lys27Gln, the homozygous genotype of CDA Ala70Thr, and the homozygous genotype of MTHFR A1298C were associated with CRC development risk. The heterozygous genotype of MTHFR A1298C variant provided highly significant protection against CRC development. Further examinations using a larger population size are needed to reliably confirm our findings