RESUMEN
Perinatal asphyxia and neonatal encephalopathy remain major causes of neonatal mortality, despite the improved availability of diagnostic and therapeutic tools, contributing to neurological and intellectual disabilities worldwide. An approach using a combination of clinical data, neuroimaging, and biochemical parameters is the current strategy towards the improved diagnosis and prognosis of the outcome in neonatal hypoxic-ischemic encephalopathy (HIE) using bioengineering methods. Traditional biomarkers are of little use in this multifactorial and variable phenotype-presenting clinical condition. Novel systems of biology-based "omics" approaches (genomics, transcriptome proteomics, and metabolomics) may help to identify biomarkers associated with brain and other tissue injuries, predicting the disease severity in HIE. Biomarker studies using omics technologies will likely be a key feature of future neuroprotective treatment methods and will help to assess the successful treatment and long-term efficacy of the intervention. This article reviews the roles of different omics as biomarkers of HIE and outlines the existing knowledge of our current understanding of the clinical use of different omics molecules as novel neonatal brain injury biomarkers, which may lead to improved interventions related to the diagnostic and therapeutic aspects of HIE.
RESUMEN
Human serum albumin (HSA) is a predominant protein in the blood. Most drugs can bind to HSA and be transported to target locations of the body. For this study, we have extracted 3-trans-feruloyl maslinic acid (FMA) from the medicinal plant Tetracera asiatica, its a non-fluorescent derivative have potent anti-cancer, anti-HIV, anti-diabetic, and anti-inflammatory activities. The binding constant of the compound with HSA, calculated from fluorescence data, was found as K(FMA)=1.42+/-0.01 x 10(8) M(-1), which corresponds to 10.9 kcal M(-1) of free energy. Furthermore, microTOF-Q mass spectrometry data showed binding of FMA at nanomolar concentrations of FMA to free HSA. The study detected a mass increase from 66,560 Da (free HSA) to 67,919 Da (HSA+drug). This indicated a strong binding of FMA to HSA, resulting in an increase of the protein's absorbance and fluorescence. The secondary structure of HSA+FMA (0.1 mM) complexes showed the protein secondary structure became partially unfolded upon interaction of FMA with HSA, as well as indicating that HSA-FMA complexes were formed. Docking experiments uncovered the binding mode of FMA in HSA molecule. It was found that FMA binds strongly in different places with hydrogen bonding at IB domain of Arg 114, Leu 115 and Asp 173.
Asunto(s)
Albúmina Sérica/química , Triterpenos/química , Sitios de Unión , Dicroismo Circular , Simulación por Computador , Humanos , Cinética , Magnoliopsida/química , Plantas Medicinales/química , Unión Proteica , Espectrometría de Fluorescencia , Relación Estructura-Actividad , Termodinámica , Triterpenos/aislamiento & purificaciónRESUMEN
Betulinic acid (BA) has anti cancer and anti-HIV activity and has been proved to be therapeutically effective against cancerous and HIV-infected cells. Human serum albumin (HSA) is the predominant protein in the blood. Most drugs that bind to HSA will be transported to other parts of the body. Using micro TOF-Q mass spectrometry, we have shown, for the first time that BA isolated from a plant (Tephrosia calophylla) binds to HSA. The binding constant of BA to HSA was calculated from fluorescence data and found to be K(BA)=1.685+/-0.01 x 10(6) M(-1), indicating a strong binding affinity. The secondary structure of the HSA-BA complex was determined by circular dichroism. The results indicate that the HSA in this complex is partially unfolded. Further, binding of BA at nanomolar concentrations of BA to free HSA was detected using micro TOF-Q mass spectrometry. The study revealed a mass increase from 65199 Da (free HSA) to 65643 Da (HSA+drug), where the additional mass of 444 Da was due to bound BA. Based on the results of this study, it is suggested that micro TOF-Q mass spectrometry is useful technique for drug binding studies.