RESUMO
Background: Acylcarnitine is one of the crucial markers of fatty acid metabolism, and examination of their level in infants can reveal several Inherited Metabolic Disorders (IDM) or Inborn errors of Metabolism (IEM). Because of the great importance of hereditary, metabolic, and other inherited disorders early diagnosis before the appearance of clinical symptoms, this study was carried out to establish a reference range for carnitine analytes and to identify acylcarnitine profiles in normal weight neonatal dried blood spots (DBS) specimens. Methods: By using liquid chromatography tandem mass spectrometry (LC-MS/MS) for neonatal screening and eventually the examination and analysis of LC-MS/MS results, 34 acylcarnitine derivatives were identified. Results: The normal range for acylcarnitine analytes with carbon numbers ranging from zero to 18, both main and the branched ones, were ultimately measured. Afterward, they were compared with the results of some other diagnostic laboratories to be verified. Conclusions: This study differed from the other findings, which could be due to diversity in population and work methods. However, the reference range of most acylcarnitine derivatives in Tehran closely aligned with this study's findings.
RESUMO
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.
Assuntos
Neoplasias da Mama/genética , MicroRNAs/genética , Receptores da Neurocinina-1/genética , Substância P/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Proliferação de Células/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Fosforilação/genética , Transdução de Sinais/genéticaRESUMO
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.