Evaluating the antibiotic resistance and frequency of adhesion markers among Escherichia coli isolated from type 2 diabetes patients with urinary tract infection and its association with common polymorphism of mannose-binding lectin gene.

The present paper aims to determine the frequency and antibiotic resistance patterns of pathogenic bacteria, the virulence factor profile of Escherichia coli and mannose-binding lectin (MBL) gene polymorphism in individuals with diabetes mellitus (DM) and urinary tract infection (UTI). The population under study was 130 individuals with type 2 diabetes mellitus (T2DM) and UTI. The patients' clinical characteristics and urine and blood samples (5 mL) were collected. Antibiotic resistance was determined using a disc diffusion method, and the results were interpreted according to CLSI. The presence of virulence genes was detected by multiplex PCR. To detect the MBL gene polymorphism, PCR and restriction fragment length polymorphism methods were applied. The predominant Gram-negative and Gram-positive bacteria included E. coli and Streptococcus spp.viridans group, respectively. Women were more susceptible to the incidence of UTI than men. The E. coli isolates showed a high level of resistance to amoxicillin-clavulanic acid (87.35%), and nitrofurantoin and ceftizoxime were the most effective antimicrobial agents for E. coli. Cefotaxime and ceftizoxime were the most effective antimicrobial agents for Enterobacter spp., norfloxacin and ciprofloxacin were the most effective antimicrobial agents for Staphylococcus epidermidis and Staphylococcus saprophyticus. papGII (52.87%) and papEF (1.14%) had the highest and lowest frequency among examined genes in E. coli isolates, respectively. The GG genotype had the highest frequency among patients with T2DM and UTI. Results showed that the detection of E. coli in individuals with an AA genotype, codon 54 of the MBL gene, can play an important role in the molecular diagnosis and timely treatment of bacterial infections in individuals with diabetes.

Stem cell therapy for hereditary breast cancer.

Both hereditary and sporadic breast cancers may develop through dysregulation of self-renewal pathways of normal mammary stem cells. Networks of proto-oncogenes and tumor suppressors that control cancer cell proliferation also regulate stem cell self-renewal and possibly stem cell aging. Breast cancer susceptibility gene (BRCA1) is a nuclear phosphoprotein expressed in many nuclear processes, including stem cell regulator, DNA damage repair, recombination, transcription, ubiquitination, cell cycle checkpoint enforcement, and centrosome regulation. In this study, we report on recent advances on the functions of embryonic, fetal, and adult stem cell progenitors for hereditary breast cancer therapies. Several molecular targeting therapies are described by activation and blocking distinct developmental signaling cascade elements, such as BRCA1, EGFR, hedgehog, Wnt/beta-catenin, and/or Notch pathways, which are frequently upregulated in cancer progenitor cells during the initiation and development of breast cancer.

Application of multiplex PCR with histopathologic features for detection of familial breast cancer in formalin-fixed, paraffin-embedded histologic specimens.

Breast cancer is the most common malignancy among females in the world. Age and familial history are the major risk factors for the development of this disease in Iran. Mutations of BRCA1 and BRCA2 genes are associated with a greatly increased risk for development of familial breast cancer. Frequency of BRCA mutations was identified in familial breast cancers (FBC) and non-familial breast cancers (NFBC) by molecular genetics, morphological and Immunohistochemical methods. Thirty forth formalin-fixed, paraffin-embedded breast tissue tumors were analyzed from 16 patients with FBC and 18 patients with NFBC. Three 5382insC mutations detected by multiplex PCR in 16 familial breast cancers. Immunohistochemical method was used to detect estrogen receptor (ER) and progesterona receptor (PR) and TP53. Comparison of ER, PR and TP53 exhibited high difference (P < 0.0001) in familial breast cancers and non-familial breast cancers. Our results demonstrated that 5382insC mutation, ER, PR, TP53, mitotic activity, polymorphism, necrosis and tubules can serve as the major risk factors for the development of FBC.

Production of novel chemotherapeutic drugs by Streptomycetes.

Chemotherapeutic drugs (CDs) for treatment of disorders such as cancer have been traditionally originated by the isolation of natural products from different environmental niches, by chemical synthesis or by a combination of both approaches thus generating semisynthetic drugs. In the last years, a number of gene clusters from several CDs biosynthetic pathways, mainly produced by Streptomycetes and belonging to the polyketides family, are being characterized. Genetic manipulation of these CDs biosynthetic pathways offer an alternative for the generation of novel CDs derivatives. These drugs have been produced by mutagenesis and screening, protoplast fusion, targetted gene disruption, gene amplification and heterologous expression of genes in other hosts or by combinatorial biosynthesis. Here we review the production and regulation of several CDs such as erythromycin and its novel derivatives by genetic manipulation in Streptomycetes.