Expression and characterization of a novel recombinant cytotoxin II from Naja naja oxiana venom: A potential treatment for breast cancer

Breast cancer (BC) is among the leading causes of mortality from cancer in women. Many of the available anticancer drugs have various side effects. Therefore, researchers are seeking novel anticancer agents particularly from natural compounds and in this regard, snake venom is still one of the main sources of drug discovery. Previous studies showed potential anticancer effects of Cytotoxin II (CTII) from Naja naja oxiana against the different types of cancers. In this study, a pET-SUMO-CTII vector was transformed into SHuffle® T7 Express, an Escherichia coli strain, for recombinant protein expression (rCTII) and the cytotoxic effects of this protein was assessed in MCF-7 cells. The flow cytometry assay was applied to measure the apoptosis and cell cycle. Also, mRNA levels of the Bax, Bcl2, P53, caspase-3, caspase-8, caspase-9, caspase-10, matrix metalloproteinases (MMP)-3, and MMP-9 were analyzed by quantitative real-time PCR to determine the underlying cellular pathways affected by rCTII. The results of this study showed that treatment with 4 μg mL−1 of rCTII enhanced apoptosis through the intrinsic and extrinsic pathways. Also, the increase of the cells' proportion in the sub-G1 phase as well as a reduction in S phase was observed. In addition, the expression of MMP-3 and MMP-9 was decreased in the treated group in comparison to the control group that may contribute to the reduced migratory ability of tumor cells. These experimental results indicate that rCTII has anti-proliferative potential, and so this protein could be a potential drug for BC therapy in combination with other drugs

Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea

Background: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. Methods: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. Results: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. Conclusions: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.info:eu-repo/semantics/publishedVersio

Additional file 1: Figure S1. of Analysis of change in gait in the ovine stifle: normal, injured, and anterior cruciate ligament reconstructed

Full factor loading plot. Points labeled by DOF_Gait point. This figure shows the full factor loadings from the principal components analysis. PC 1 (35%) is the X axis, PC 2 (20%) is the Y axis. Each factor is labeled by [DOF]_[Location within the gait cycle]. For example, in quadrant 2, ml_ho represents the factor loading for [Medial/Lateral]_[Hoof Off]. (JPG 1433 kb

"The spectrum of primary immunodeficiency disorders in Iran "

Epidemiological studies have shown wide geographical and racial variation in the prevalence and patterns of immunodeficiency disorders. To determine the frequency of primary immunodeficiencies (PID) in Iran, the Iranian primary Immunodeficiencies Registry (IPIDR) was organized in 1999. the diagnosis of immunodeficiency in our patients was based on standard criteria. The patient’s data were extracted, by using a uniform questionnaire from their hospital records. Three hundred and twenty eight patients with PID have been registered in our registry till 2000. Among these patients, the following frequencies were found: predominantly antibody deficiency in 48.48% of patients (n=159), T-cell disorders in 25.91% (n=85), phagocytic disorders in 24.7% (n=81), and complement deficiencies in 0.91% (n=3). Common variable immunodeficiency was the most frequent disorder (n=73), followe by chronic granulomatous disease (n=55), ataxia telangiectasia (n=39), x-linked agammaglobulinemia (n=35), selective IgA deficiency (n=34). This study reveals that antibody deficiencies are the most frequent diagnosed primary immunodeficiency disorder in our patients, which is similar to that observed in other registries. A comparative study shows some differences between our results and other registrie

Consanguinity in primary immunodeficiency disorders; the report from Iranian primary immunodeficiency registry

Problem: Primary Immunodeficiency Disorders (PiD) are a heterogeneous group of genetic disorders, with different modes of inheritance. This study was accomplished in order to determine the frequency of consanguineous marriages in the families of patients with PiD. Method: In this study, the records 515 Iranian PiD patients were reviewed during a 25-year period. Results: The mean proportion of consanguineous marriages was 65.6 among PiD patients, while the overall rate was 38.6 in the country. The rate of consanguinity was 77.8 in cellular immunodeficiencies, 75.8 in combined immunodeficiencies, 72.5 in defects of phagocytic function, 58.6 in other immunodefiiencies, 54.1 in predominantly antibody deficiencies, and 50 in complement deficiencies. Moreover all patients with immunodeficiency associated with other diseases had consanguineous parents. Such marriages were most common in the parents of patients with Chediak-Higashi syndrome, severe combined immunodeficiencies, primary CD4 deficiency, ataxia-telangiectasia, seletive IgG class deficiencies, chronic granulomatous disease, and Schwachman syndrome. Conclusions: It is important to inform the general population about the dangers of consanguinity, which is very common in some areas such as Iran. Premarital examination to avoid genetic diseases could be suggested, especially in a community where the rate of consanguineous marriage is high. © 2006 The Authors Journal compilation © 2006 Blackwell Munksgaard