The prevalence, intensity and viability of hydatid cysts in slaughtered animals in the Ardabil province of Northwest Iran

In a cross-sectional study, a total of 5381 slaughtered animals, namely 928 cattle, 243 buffaloes, 3765 sheep and 445 goats were inspected macroscopically for hydatid cysts in northwest Iran, with prevalence values of 38.3%, 11.9%, 74.4% and 20%, respectively, being recorded. Prevalences were higher in females compared with males, but a significant difference (P < 0.001) was only found in sheep and cattle. Most cases which were condemned were seen in the lungs of sheep (13.4%) indicating that sheep are the most important intermediate hosts for Echinococcus granulosus in this area.     

Nanosized paclitaxel-loaded niosomes: formulation,in vitro cytotoxicity,and apoptosis gene expression in breast cancer cell lines

Molecular Biology Reports - In this study, the optimized niosomal formulation containing paclitaxel using non-ionic surfactants and cholesterol was designed and its cytotoxic effects against...     

PIK3CA hotspot mutations p. H1047R and p. H1047L sensitize breast cancer cells to thymoquinone treatment by regulating the PI3K/Akt1 pathway

Background

Nigella sativa (N. sativa) exhibits anti-inflammatory, antioxidant, antidiabetic, antimetastatic and antinociceptive effects and has been used to treat dozens of diseases. Thymoquinone (TQ) is an important and active component isolated from N. sativa seeds. Inhibition of cancer-associated activating PIK3CA mutations is a new prospective targeted therapy in personalized metastatic breast cancer (MBC). TQ is reported to be an effective inhibitor of the PI3K/Akt1 pathway in MBC. This study aimed to evaluate the in vitro antitumor effect of TQ in the context of two PIK3CA hotspot mutations, p. H1047R and p. H1047L.

Methods and results

Molecular dynamics, free energy landscapes and principal component analyses were also used to survey the mechanistic effects of the p. H1047R and p. H1047L mutations on the PI3K/Akt1 pathway. Our findings clearly confirmed that the p. H1047R and p. H1047L mutants could reduce the inhibitory effect of ΔNp63α on the kinase domain of PIK3CA, resulting in increased activity of PI3K downstream signals. Structurally, the partial disruption of the interaction between the ΔNp63α DNA binding domain and the PIK3CA kinase domain at residues 114–359 and 797–1068 destabilizes the conformation of the activation loop and modifies the PIK3CA/ΔNp63α complex. Alongside these structural changes, we found that TQ treatment resulted in high PI3K/Akt1 pathway inhibition in p. H1047R and p. H1047L-expressing cells versus wild-type cells.

Conclusions

These two PIK3CA hotspot mutations therefore not only contribute to tumor progression in patients with MBC but may also serve as targets for the development of novel small molecule therapeutic strategies.

     

Evaluation of expression CXCL8 chemokine and its relationship with oocyte maturation and embryo quality in the intracytoplasmic sperm injection method

Molecular Biology Reports - The present study aimed to evaluate the expression of the chemokine CXCL8 in both mRNA and protein levels in the serum, follicular fluid (FF), and cumulus cells (CCs)...     

Multiple loci are associated with white blood cell phenotypes

White blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse ancestral backgrounds.     

Modulating furin activity with designed mini-PDX peptides: synthesis and in vitro kinetic evaluation

A peptide was designed from reactive site loop structure of alpha1 Antitrypsin Portland known as alpha1 PDX as a novel mini-PDX inhibitor of furin. The sequence was derived from (367-394) that contains the crucial furin cleavage motif RIPR382. A P3 mutant replacing Ile380 by Leu was prepared as a first model peptide. A Cys residue was inserted at each terminal of the peptide for purpose of cyclisation which was accomplished by air or iodine-induced oxidation. This mini-PDX peptide both cyclic and acyclic form inhibited in vitro furin activity (IC50 in nM) when measured against either substrates Boc-RVRRdown double arrow MCA or QVEGF-C [Abz-QVHSIIRRdown double arrow SLP-Y(NO2)-A-CONH2, Abz=2-amino benzoic acid and Y(NO2)=3-nitro tyrosine], latter being derived from vascular endothelial growth factor-C (VEGF-C) processing site. The geometrically constrained structure mimicking PDX reactive loop is crucial for enzyme inhibition. Our study further revealed that both mini-PDX peptides inactivate furin in a slow tight binding manner, with disulfide-bridged cyclic form being slightly more potent. Unlike PDX, these peptides inhibit furin via a different mechanistic pathway. The study provides an alternate strategy for development of efficient peptide-based inhibitors of Proprotein Convertases including furin.     

Relationship of stimulated whole saliva cortisol level with the severity of a feeling of dry mouth in menopausal women

doi: 10.1111/j.1741‐2358.2010.00403.x Relationship of stimulated whole saliva cortisol level with the severity of a feeling of dry mouth in menopausal women Objectives: To evaluate the relationship of stimulated whole saliva cortisol level with the severity of a feeling of dry mouth (DM) in menopausal women. Background: A feel of DM is a major complaint for many elderly individuals and strongly associated with the menopause. The exact mechanisms that mediate sensation of DM in menopausal women have not been firmly established. Methods: A case–control study was carried out on 104 selected menopausal women with/without a feeling of DM, conducted at the Clinic of Oral Medicine, Tehran University of Medical Sciences. Xerostomia Inventory (XI) score was used as an index of DM severity. Stimulated whole saliva cortisol concentration (stimulated by chewing standard‐sized paraffin for 60 s) was measured by ELISA. Statistical analysis by Student’s t‐test and Spearman correlation was used. Results: The mean cortisol concentration of saliva, but not saliva cortisol output, was significantly higher in the cases than in the controls. There was significant positive correlation between XI score and concentration (r = 0.357, p = 0.000) or output (r = 0.223, p = 0.017) of stimulated whole saliva cortisol. Conclusions: It appears that stimulated whole saliva cortisol is high in menopausal women with a feeling of DM.