Ishita Gupta

Low folate and vitamin B12 nourishment is common in Omani children with newly diagnosed autism

OBJECTIVE Arab populations lack data related to nutritional assessment in children with autism spectrum disorders (ASDs), especially micronutrient deficiencies such as folate and vitamin B12. METHODS To assess the dietary and serum folate and vitamin B12 statuses, a hospital-based case-control study was conducted in 80 Omani children (40 children with ASDs versus 40 controls). RESULTS The ASD cases showed significantly lower levels of folate, vitamin B12, and related parameters in dietary intake and serum levels. CONCLUSION These data showed that Omani children with ASDs exhibit significant deficiencies in folate and vitamin B12 and call for increasing efforts to ensure sufficient intakes of essential nutrients by children with ASDs to minimize or reverse any ongoing impact of nutrient deficiencies.

Impact of nutrition on serum levels of docosahexaenoic acid among Omani children with autism

OBJECTIVES Autism is a lifelong neurodevelopmental disorder of early childhood. Dietary supplementation of the ω-3 fatty acid (docosahexaenoic acid [DHA]) during prenatal and postnatal life is considered a protective dietary intervention strategy to minimize the risk for autism spectrum disorder (ASD). To our knowledge, no relevant studies have been conducted in the Middle East investigating the status of DHA among children with autism during early childhood. The aim of this study was to investigate the serum levels and dietary intake status of DHA among Omani children recently diagnosed with ASD. METHODS The present case-control study involved 80 Omani children (<5 y), 40 cases and 40 controls matched for age and sex. A semi-quantitative food frequency questionnaire was used to assess dietary intake of all the participants, while serum levels of DHA were measured using high-performance liquid chromatography. RESULTS Our results showed that children with ASD had lower dietary consumption of foodstuff containing DHA, as well as lower serum levels of DHA than controls. CONCLUSION The present finding from Oman supports the view of other studies that there are low serum levels of DHA among children with ASD.

Simultaneous inhibition of cell-cycle, proliferation, survival, metastatic pathways and induction of apoptosis in breast cancer cells by a phytochemical super-cocktail: genes that underpin its mode of action.

Traditional chemotherapy and radiotherapy for cancer treatment face serious challenges such as drug resistance and toxic side effects. Complementary / Alternative medicine is increasingly being practiced worldwide due to its safety beneficial therapeutic effects. We hypothesized that a super combination (SC) of known phytochemicals used at bioavailable levels could induce 100% killing of breast cancer (BC) cells without toxic effects on normal cells and that microarray analysis would identify potential genes for targeted therapy of BC. Mesenchymal Stems cells (MSC, control) and two BC cell lines were treated with six well established pro-apoptotic phytochemicals individually and in combination (super cocktail), at bioavailable levels. The compounds were ineffective individually. In combination, they significantly suppressed BC cell proliferation (>80%), inhibited migration and invasion, caused cell cycle arrest and induced apoptosis resulting in 100% cell death. However, there were no deleterious effects on MSC cells used as control. Furthermore, the SC down-regulated the expression of PCNA, Rb, CDK4, BcL-2, SVV, and CD44 (metastasis inducing stem cell factor) in the BC cell lines. Microarray analysis revealed several differentially expressed key genes (PCNA, Rb, CDK4, Bcl-2, SVV, P53 and CD44) underpinning SC-promoted BC cell death and motility. Four unique genes were highly up-regulated (ARC, GADD45B, MYLIP and CDKN1C). This investigation indicates the potential for development of a highly effective phytochemical combination for breast cancer chemoprevention / chemotherapy. The novel over-expressed genes hold the potential for development as markers to follow efficacy of therapy.

A study on knowledge, attitude, and practice towards premarital carrier screening among adults attending primary healthcare centers in a region in Oman

BackgroundDespite that hereditary diseases are widespread among the Arab population due to high rates of consanguineous marriages, research regarding community awareness towards premarital carrier screening in some countries such as Oman, is extremely scarce. This study aimed to investigate knowledge and attitude towards premarital carrier screening (PMCS) in Oman.MethodsA cross-sectional study was conducted using a self-administered questionnaire which was distributed to 400 Omani adults aged 20–35 who attended primary healthcare institutions at the South Batinah Governorate in Oman.ResultsThe majority of the participants (84.5%) believed that PMCS was necessary, and about half of them (49.5%) supported the view of making PMCS compulsory. On the contrary, approximately one third (30.5%) of the participants reported that they were not in favor of taking the blood screening test. Overall, unwillingness to perform pre-marital testing was associated with female gender, younger age, being single, less education, and increased income.ConclusionDespite the relatively high level of knowledge, about one third of the participants were still reluctant to carry out premarital testing. Such attitude calls for immediate need for community-based campaigns to encourage the public to do premarital testing.

TGF-β2: A Novel Target of CD44-Promoted Breast Cancer Invasion

We have developed a tetracycline (tet)-off regulated expression of CD44s gene in the breast cancer (BC) cell line MCF-7 (B5 clone) and identified TGF-β2 (Transforming Growth Factor beta-2; 3 fold induction) as a potential CD44-downstream transcriptional target by microarray analysis. To further validate this finding, the same RNA samples, used for microarray analysis and their corresponding protein lysates, collected from the BC cell line MCF-7-B5, were examined for CD44 expression in the presence of HA. Our results showed that TGF-β2 mRNA levels were significantly elevated following the removal of tetracycline at 18, 24, and 48 h post-HA stimulation compared to the parental cells. Furthermore, the TGF-β2 precursor protein increased in a time-dependent pattern upon HA-stimulation and in the absence of tetracycline. More interestingly, inhibition of CD44 gene by RNAi method decreased TGF-β2 expression upon HA-stimulation, and subsequently inhibited BC cell invasion in vitro. In addition to identifying TGF-β2 as a target for HA/CD44 signaling, this data suggests that ATF/CREB might be a potential transcription factor linking HA/CD44 activation to TGF-β2 transcription and additional experiments are required for a better understanding of the molecular mechanisms underpinning the novel function of the CD44/ TGF-β2 signaling pathway in breast cancer metastasis.

Potato chips and childhood: What does the science say? An unrecognized threat?

With recent rapid progress in technology and advancing lifestyle associated with modernization, individuals are consuming increasing quantities of unhealthy food, a major risk factor for the onset of a variety of diseases. In particular, fried potato chips (FPCs), are the most commonly consumed snack, especially by children. However, research in the field of nutrition demonstrated that FPCs encompass significant quantities of acrylamide, a known carcinogen and neurotoxin. Thus, frequent intake of FPC, especially at younger age, might generate cumulative amounts of acrylamide in the body, thereby silently increasing the risk for various diseases. Although intake of a balanced diet can prevent this scenario, further measures should be set to overcome the oxidative damage from fried food. This review outlines existing scientific evidence suggesting an urgent need for systematic study regarding the health effects of consumption of FPC and French fries in the general population.

Novel Mutation in the CFTR Gene of Cystic Fibrosis Patients in Oman

Introduction: Cystic fibrosis (CF) is the most common lethal autosomal recessive disorder among Caucasians (1: 3,000). In CF, the CFTR gene is frequently mutated, with ΔF508del being the largely common mutation in Caucasians. Our preliminary pilot study in Omani population revealed a CF prevalence of 1:2,738. Objective: The objective of the present study was to determine the most common CFTR mutations in the Omani patients to establish a proper molecular genetics diagnostic basis of CF in Oman. Methods: Blood Genomic DNA samples from Omani patients were examined by PCR and sequencing analyses for the entire coding sequence of the CFTR gene were performed. Results: The innovative aspect of this study was the identification of a novel CF-causing mutation, L578delTA. Furthermore, in contrast to the west, p.S549R appears to be the most common mutation in Oman (65.2% for S549R and 13% for ΔF508). Conclusion: The mutation spectrum of CF in Oman revealed six CF-causing mutations, p.S549R, ΔF508, 3120+1G>A, L578delTA, p.A357T and 3849+10kbC->T. These findings will ultimately pave the way towards the development of molecular genetic tests in Oman to confirm the diagnosis of CF and serve the patient care and management.

BRIP1 overexpression is correlated with clinical features and survival outcome of luminal breast cancer subtypes

In Oman, breast cancer is most common, representing approximately more than 25% of all cancers in women. Relatively younger populations of patients (25–40 years) present surprisingly with an aggressive phenotype and advanced tumor stages. In this study, we investigated differential gene expressions in Luminal A, Luminal B, triple-negative and Her2+ breast cancer subtypes and compared data to benign tumor samples. We identified a potential candidate gene BRIP1, showing differential expression in the four breast cancer subtypes examined, suggesting that BRIP1 has the profile of a useful diagnostic marker, suitable for targeted therapeutic intervention. RT-qPCR and Western blotting analysis showed higher BRIP1 expression in luminal samples as compared to triple-negative subtype patient’s samples. We further screened BRIP1 for eventual mutations/SNPs/deletions by sequencing the entire coding region. Four previously identified polymorphisms were detected, one within the 5′-UTR region (c.141-64G > A) and three in the BRCA-binding domain (c.2755T > C, c.2647G > A and c.3411T > C). Kaplan–Meier analysis revealed that patients with overexpression of BRIP1 displayed a poor survival rate (P < 0.05). BRIP1 has a dual function of an oncogene and a tumor suppressor gene in addition to its role as a potential biomarker to predict survival and prognosis. Data obtained in this study suggest that BRIP1 can plausibly have an oncogenic role in sporadic cancers.

Molecular genetics complexity impeding research progress in breast and ovarian cancers (Review)

Breast and ovarian cancer are heterogeneous diseases. While breast cancer accounts for 25% of cancers worldwide, ovarian cancer accounts for 3.5% of all cancers and it is considered to be the most lethal type of cancer among women. In Oman, breast cancer accounts for 25% and ovarian cancer for 4.5% of all cancer cases. Various risk factors, including variable biological and clinical traits, are involved in the onset of breast and ovarian cancer. Although highly developed diagnostic and therapeutic methods have paved the way for better management, targeted therapy against specific biomarkers has not yet shown any significant improvement, particularly in triple-negative breast cancer and epithelial ovarian cancer, which are associated with high mortality rates. Thus, elucidating the mechanisms underlying the pathology of these diseases is expected to improve their prevention, prognosis and management. The aim of the present study was to provide a comprehensive review and updated information on genomics and proteomics alterations associated with cancer pathogenesis, as reported by several research groups worldwide. Furthermore, molecular research in our laboratory, aimed at identifying new pathways involved in the pathogenesis of breast and ovarian cancer using microarray and chromatin immunoprecipitation (ChIP), is discussed. Relevant candidate genes were found to be either up- or downregulated in a cohort of breast cancer cases. Similarly, ChIP analysis revealed that relevant candidate genes were regulated by the E2F5 transcription factor in ovarian cancer tissue. An ongoing study aims to validate these genes with a putative role as biological markers that may contribute to the development of targeted therapies for breast and ovarian cancer.

Molecular Evidence of Helicobacter Pylori Infection in Prostate Tumors

Objectives: To determine whether Helicobacter pylori (H. pylori) is detectable in both benign prostatic hyperplasia (BPH) and prostate cancer (PCa). Epidemiological studies have shown significant associations between infective chronic prostatitis and prostatic carcinoma. Many bacteria have been found in the prostate of patients with chronic prostatitis, BPH, and PCa. Methods: One hundred consecutive patients with prostate diseases were enrolled in the study. Detection of H. pylori DNA in prostate tissue from patients with BPH and PCa was performed using both immunohistochemistry and PCR, and the results were confirmed by DNA sequencing. Odds ratios and the Fisher Exact test were used for the analysis of the associations between the variables. Results: Among the patients, 78% had BPH and 19% had PCa. While immunohistochemistry showed no positive sample for H. pylori, PCR combined with sequencing detected H. pylori DNA in prostate tissue samples from 5 patients. However, statistical analysis of the data showed that BPH and PCa are not significantly associated with the presence of H. pylori DNA in prostate tissue (odds ratio = 0.94, 95% confidence interval = 0.09-23.34, one-tailed Chi-square value = 0.660, p > 0.05). The limitation of this study was the small number of PCa patients. Conclusions: This study provides, for the first time, molecular evidence of the presence of H. pylori DNA in prostatic tissue of patients with BPH and PCa. It paves the way for further comprehensive studies to examine the association of H. pylori infection with BPH and PCa.