BackgroundThe contribution of genetic factors to the development of breast cancer in the admixed and consanguineous population of the western region of Saudi Arabia is thought to be significant as the disease is early onset. The current protocols of continuous clinical follow-up of relatives of such patients are costly and cause a burden on the usually over-stretched medical resources. Discovering the significant contribution of BRCA1/2 mutations to breast cancer susceptibility allowed for the design of genetic tests that allows the medical practitioner to focus the care for those who need it most. However, BRCA1/2 mutations do not account for all breast cancer susceptibility genes and there are other genetic factors, known and unknown that may play a role in the development of such disease. The advent of whole-exome sequencing is offering a unique opportunity to identify the breast cancer susceptibility genes in each family of sufferers. The polymorphisms/mutations identified will then allow for personalizing the genetic screening tests accordingly. To this end, we have performed whole-exome sequencing of seven breast cancer patients with positive family history of the disease using the Agilent SureSelect™ Whole-Exome Enrichment kit and sequencing on the SOLiD™ platform.ResultsWe have identified several coding single nucleotide variations that were either novel or rare affecting genes controlling DNA repair in the BRCA1/2 pathway.ConclusionThe disruption of DNA repair pathways is very likely to contribute to breast cancer susceptibility in the Saudi population.

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Background Chemotherapy remains to be the method of choice used by clinicians to treat acute myeloid leukemia (AML) patients. However, the most common problem usually faced in the course of treatment is multidrug resistance (MDR). Nowadays, combination therapy involving natural products as adjuvant therapy to chemotherapy and radiotherapy has been used for many of health problems. Coumarin is a natural compound with known chemotherapeutic activity, as well as other pharmacological properties. We focused on the combination of coumarin and doxorubicin in overcoming of drug-resistance in acute myeloid leukemia. Methods Cell viability, Apoptotic and necrotic cell death with FACS, oxidative stress detection, and protein expression analysis were used in this study. Results Coumarin as a single drug exerts a significant cell death on Human acute myeloid leukemia (HL60); however, it does not show the same effect on drug-resistant acute myeloid leukemia (HL60/ADR). Comparing the effects of doxorubicin and coumarin as single drugs versus a combination of coumarin and doxorubicin showed a significant apoptotic cell death. Conclusion In AML patients, the development of multiple drug resistance (MDR) is the biggest challenge in treating AML patients. Combination therapy with coumarin may be a good choice to overcome the drug resistance in AML patients.

Background: The antioxidant, hypoglycemic, and insulin-enhancing effects of ginger and cinnamon were previously confirmed in experimental and human studies, while the combined effect of ginger and cinnamon was not thoroughly investigated until now.Objectives: This study was designed to assess the antidiabetic effect of combined administration of ginger (Zingiber officinale Roscoe) and cinnamon (Cinnamomum cassia L.) in streptozotocin (STZ)-induced diabetic rats compared to metformin and to explain the mechanism behind this effect.Materials and methods: STZ was utilized to induce diabetes mellitus in male Sprague–Dawley rats. Assessments of fasting blood glucose level (BGL), the total antioxidant capacity (TAC), serum insulin, HOMA-IR, and HOMA–β cells were performed. Pancreatic gene expression of β-catenin and p53 was assessed using RT-PCR. Assessment of histopathological alterations of pancreatic islet cells was performed using routine and immunohistochemical techniques.Results: BGL significantly decreased (p = 0.01), while serum insulin and TAC significantly increased (p < 0.001) in both metformin- and ginger plus cinnamon–treated groups compared to the untreated diabetic group. HOMA–β cell index significantly increased (p = 0.001) in ginger plus cinnamon, indicating their enhancing effect on insulin secretion in diabetic conditions. p53 gene expression was significantly upregulated (p < 0.001), while β-catenin was insignificantly downregulated (p = 0.32) in ginger plus cinnamon–treated groups. Insulin immunoexpression in β cells significantly increased (p = 0.001, p = 0.004) in metformin- and ginger plus cinnamon–treated groups, respectively.Conclusions: The combined administration of ginger and cinnamon has a significant hypoglycemic and antioxidant effect in STZ-induced diabetes mostly through enhancing repair of islet cells mediated via upregulation of pancreatic p53 expression. Therefore, testing this effect in diabetic patients is recommended.

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Background: Hepatocellular carcinoma (HCC) is one of the most serious cancers worldwide.Even with recent developments, there has been slight progress in improving the survival rate of HCC patients. Current therapies are accompanied by marked side effects beside incomplete recovery. Therapy by Herbal products proved effective anticancer. Aim: Screening of the apoptotic and anti-proliferative effects of Rhazya stricta (R. stricta), nanoparticles which locally known as " Harmal" against highly aggressive HCC in vitro study. Procedures: R. Stricta Nano particles was gained by exposing R. Stricta sheets to ball milling process to convert particles into Nano scale diameter which examined by scanning electron microscopy (SEM) . Cytotoxicity of different concentrations of R.stricta nanoparticles (0.0, 100 and 500 µg/ml) was evaluated via its effects on the mRNA expression of Bax and Bcl-2 apoptosis related genes in Hep G-2 and Huh-7cell lines using real-time quantitative PCR analysis, MTT assay and FACS analysis Results: It is clear from SEM images that R.Stricta nanoparticles are predominantly spherical in shape and polydispersity with particle size around 100 nm. After 24 and 48 hours, R.stricta nanoparticles showed a significant cytotoxic effect on all cell lines at 500 μg/ml (p<0.05) but has a high significant effect on decreasing Hep G-2 cell viability with 100 and 500 μg/ml of R.stricta nanoparticles Hr(p<0.001) compared with other cell lines. Conclusion and clinical relevance:Moving on gene expression,MTT assay and FACS analysis, it could concluded that the R. stricta, nanoparticles produced apoptosis in Hep G-2 and Huh-7 cell lines

Pumpkin has received significant attention due to its nutritional compounds that have antioxidant, antifatigue, and anti-inflammatory effects. This study is aimed at assessing the antidepressant-like effect of L. Cucurbita pepo, sweet pumpkin, in an animal model of chronic unpredictable mild stress (CUMS) and investigating its effect on the histological structure of hippocampus compared to fluoxetine. Forty male albino rats assigned into the negative control, positive control (CUMS), and Flu-treated and pumpkin-treated groups ( n = 10 ) were utilized in this study. Exposing rats to CUMS continued for 28 days, and treatments used were applied during the last 14 days of exposure. Behavioral, biochemical, and histopathological changes were assessed after 28 days. In this study, pumpkin significantly reduced the immobility time ( p = 0.02 ), corticosterone ( p < 0.001 ), TNF-α, IL-6 ( p < 0.001 ), and malondialdehyde ( p = 0.003 ), whereas it significantly increased the level of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX) in the serum of rats exposed to CUMS. Pumpkin markedly relieved the degenerative and atrophic changes observed in the CA3 region and the dentate gyrus of the hippocampus. It significantly reduced caspase-3 and increased glial fibrillary acidic protein (GFAP) immunoexpression in the CA3 and DG. In conclusion, administration of pumpkin extract improved the behavioral, biochemical, and hippocampal pathological alternations induced in rats after exposure to CUMS in a comparable pattern to fluoxetine. This study highlighted the potential efficacy of pumpkin in alleviating depression disorder either alone or in conjugation with conventional antidepressant therapy.