The neuropeptide substance P (SP) triggers a variety of tumor-promoting signaling pathways through the activation of neurokinin-1receptor (NK1R), a class of neurokinin G protein-coupled receptors superfamily. Recent researches in our and other laboratories have shown the overexpression of both SP and NK1R in breast cancer (BC) patients. SP/NK1R signaling is strongly implicated in the pathogenesis of BC through affecting cell proliferation, migration, metastasis, angiogenesis, and resistance. Therefore, SP/NK1R signaling responses must be rigorously regulated; otherwise, they would contribute to a more aggressive BC phenotype. Recently, microRNAs (miRNAs) as a specific class of epigenetic regulators have been shown to regulate NK1R and thus, controlling SP/NK1R signaling responses in BC. This review summarizes the current knowledge of the role of SP/NK1R signaling and its therapeutic potentials in BC. We also provide an overview regarding the effects of miRNA-mediated NK1R regulatory mechanisms in controlling BC tumorigenesis to gain a clearer view and thus better management of cancer.

Objective: Inborn errors of metabolism (IEMs) are disorders with various manifestations that occur mainly in the pediatric population. In countries where consanguineous marriage is common, the association between consanguinity and IEMs is highly important. No studies have been conducted in Iran examining the impact of consanguinity on IEMs. Methods: In this retrospective study, the incidences of metabolic disorders were evaluated for the years 2006 through 2016 in the North East Iran Regional Diagnostic Laboratory (Pardis Clinical and Genetic Laboratory). A total of 13,327 infants with clinical symptoms were referred and investigated for IEMs. Newborn screening was performed on samples from all patients suspected of having IEMs. Results: Of 13,327 infants examined, 60 different IEMs were diagnosed in 1,118. The most frequent disorders among our patients were glucose-6-phosphate dehydrogenase deficiency (G6PDD) (14.04%), methylmalonic and propionic acidurias (MMA/PA) (9.12%), phenylketonuria (PKU) (8%), and isovaleric acidemia (IVA) (6.98%). A significant difference was found in the prevalence of amino acid disorders between the offspring of consanguineous and those of non-consanguineous parents. No statistically significant differences were found between the 2 groups for organic or fatty acids, carnitine or urine cycles, or lysosomal storage disorders. A total of 707 of the 1,118 infants with metabolic diseases (63.24%) were children of consanguineous parents. These findings show that consanguinity can be an important factor in the inheritance of recessive mutations in a homozygous state. Conclusion: This study found a greater frequency of metabolic diseases in offspring of consanguineous parents than in those of non-consanguineous parents in a population with a high rate of consanguinity.

Objectives: The aim of the present study was to develop a robust and easy to use high performance liquid chromatography (HPLC) to analyze 25(OH)D3 in human serum. Background: Vitamin D is a fat-soluble steroid hormone precursor that is mainly produced in the skin by exposure to sunlight. It is also supplied in the diet and plays a pivotal role in calcium homeostasis and skeletal metabolism throughout life. Methods: To assess its analytical performance, we used the RECIPE HPLC Complete Kit and an HPLC-UV instrument. Our HPLC results were compared with a validated electrochemiluminescence method. Results: The method was linear for the lower limit of quantification from 3 ng/l up to at least 200 ng/l for 25(OH) D3, with the following equation for the regression line: y = 0.172 X + 2.45 (R 2 = 0.989). Intra-assay precision was determined by extracting and quantifying 10 serum replicates from one patient. The mean was 37.875 ng/ml, the standard deviation was 0.22, and the coefficient of variation was 0.58%. Comparisons of results demonstrated good agreement between HPLC and ECL methods (R 2 = 0.883). Conclusion: The HPLC assay demonstrates excellent linearity, acceptable accuracy and precision, and good agreement with a validated ECL method. The simple sample preparation and ease of use make it practical for the routine clinical laboratory.

Background: Hemoglobin (Hb) is a hemeprotein with two linked pairs of globin chains. Each chain is connected to a heme residue in its center. Hemoglobinopathies are divided into quantitative and qualitative defects in globin synthesis. Hemolysis is a pre-analytical problem that reduces quality of sample for measurement of many analytes. Methods: Blood samples from 311 female and 189 male subjects with normal and abnormal Hb electrophoresis patterns were studied. Three milliliters of whole blood was obtained from all subjects and transferred into EDTA tubes. To analyze hemolysis, 1.5 ml of blood from each tube was aliquoted and frozen, and the remaining blood was stored at 4°C for 24 h. Hemoglobin was measured in both hemolyzed and non-hemolyzed samples by capillary electrophoresis. Results and discussion: Data was analyzed with linear regression. The results were linear for the lower limit of detection of 9, 0.5, and 0.1% up to at least 99.5, 6.6, and 99.4% for HbA, HbA 2 , and HbF, respectively. Method comparison demonstrated good agreement between non-hemolyzed and hemolyzed conditions for hemoglobin measurement. Conclusion: Use of hemolyzed samples had no effected on hemoglobin measurements.

Purpose Breast cancer (BC) is the most frequent malignancy with a high morbidity and mortality rate among women that can be initiated and be progressed through activating the neurokinin-1 receptor (NK1R) by substance P (SP), a highly conserved member of the tachykinin peptide family. The oxidative stress-mediated role of the SP/NK1R system results in BC pathogenesis is not entirely understood. Therefore, this study was designed to shed light on the link between SP/NK1R and cellular redox state in MCF-7 breast cancer cells. Methods Aprepitant IC50 was measured by resazurin assay. Reactive oxygen species were assessed utilizing DCFDA assay. Thioredoxin (Txn) and miR-325-3p genes expression were determined through Real-Time PCR. To evaluate the Txn protein expression, western blot analysis was performed. Results We found that SP elevated ROS production in these cells. furthermore, SP leads to a remarkable down-regulation of miR-325-3p and thioredoxin (Trx) target genes and protein expression of Trx in MCF-7 cells. In addition, aprepitant inhibited SP's effects; therefore, it decreased ROS accumulation, and up-regulated Trx and miR-325-3p genes, suggesting that aprepitant may render antioxidant properties through Trx. Conclusion Oxidative stress could have an essential role in BC pathogenesis via activating the NK1R by SP. SP can decrease the BC cell's antioxidative capacity by reducing the Trx gene and protein and miR-325-3p gene. Therefore, it causes an increase in ROS production and oxidative damage. the present investigation indicates that the SP/NK1R system might be an appealing and promising therapeutic target against BC.