Zinc concentrations in plasma and hair were measured in 703 children, aged between 1 and 6 yr, and correlated with parameters of physical development. In the first group of 187 children brought to the Child Health Clinic for routine observation there was a positive correlation of hair zinc content and height for age, with an increased prevalence of low hair zinc content in children of shorter stature. A second group of 303 children in nurseries and kindergartens in Beijing exhibited a hair zinc content of 92 micrograms/g, and 34% of these had very low zinc values below 70 micrograms/g. The third group consisted of 213 children who were brought into the outpatient clinic for a variety of complaints, including pica, anorexia, and poor growth; these had significantly lower values of zinc in hair and plasma than well-nourished children and responded to zinc supplementation with improvement of growth and the disappearance of pica and anorexia. These results suggest that the diet consumed by the population studied may be marginal or inadequate in its content of available zinc.
Glioblastomas (GBMs), are the most common intrinsic brain tumors in adults and are almost universally fatal. Despite the progresses made in surgery, chemotherapy, and radiation over the past decades, the prognosis of patients with GBM remained poor and the average survival time of patients suffering from GBM was still short. Discovering robust gene signatures toward better understanding of the complex molecular mechanisms leading to GBM is an important prerequisite to the identification of novel and more effective therapeutic strategies. Herein, a comprehensive study of genome-scale mRNA expression data by combining GBM and normal tissue samples from 48 studies was performed. The 147 robust gene signatures were identified to be significantly differential expression between GBM and normal samples, among which 100 (68%) genes were reported to be closely associated with GBM in previous publications. Moreover, function annotation analysis based on these 147 robust DEGs showed certain deregulated gene expression programs (e.g., cell cycle, immune response and p53 signaling pathway) were associated with GBM development, and PPI network analysis revealed three novel hub genes (RFC4, ZWINT and TYMS) play important role in GBM development. Furthermore, survival analysis based on the TCGA GBM data demonstrated 38 robust DEGs significantly affect the prognosis of GBM in OS (p < 0.05). These findings provided new insights into molecular mechanisms underlying GBM and suggested the 38 robust DEGs could be potential targets for the diagnosis and treatment.
Vorinostat (SAHA) with great therapeutic potential has been approved by the FDA for the treatment of cutaneous T-cell lymphoma as the first HDACs inhibitor, but the drawbacks associated with hydroxamic acid group (poor stability, easy metabolism, weak binding ability to class IIa isozymes, and poor selectivity) have been exposed during the continuous clinical application. Based on the pharmacophore of HDAC inhibitors, two series of compounds with novel zinc binding group (ZBG) were designed and synthesized, and the antitumor bioactivities were evaluated in four human cancer cell lines (A549, Hela, HepG2, and MCF-7). Among the synthesized compounds, compounds a6, a9, a10, b8, and b9 exhibited promising inhibitory activities against the selected tumor cell lines, especially compounds a9 and b8 on Hela's cytostatic activity (a9: IC 50 = 11.15 ± 3.24 µM; b8: IC 50 = 13.68 ± 1.31 µM). The enzyme inhibition assay against Hela extracts and HDAC1&6 subtypes showed that compound a9 had a certain broad-spectrum inhibitory activity, while compound b8 had selective inhibitory activity against HDAC6, which was consistent with Western blot results. In addition, the inhibitory mechanism of compounds a9 and b8 in HDAC1&6 were both compared through computational approaches, and the binding interactions between the compounds and the enzymes target were analyzed from the perspective of energy profile and conformation. In summary, the compounds with novel ZBG exhibited certain antitumor activities, providing valuable hints for the discovery of novel HDAC inhibitors.
Background Metabolites present in human urine can be influenced by individual physiological parameters (e.g., body mass index [BMI], age, and sex). Observation of altered metabolites concentrations could provide insight into underlying disease pathology, disease prognosis and diagnosis, and facilitate discovery of novel biomarkers. Methods Quantitative metabolomics analysis in the urine of 183 healthy individuals was performed based on high‐resolution liquid chromatography–mass spectrometry (LC–MS). Coefficients of variation were obtained for 109 urine metabolites of all the 183 human healthy subjects. Results Three urine metabolites (such as dehydroepiandrosterone sulfate, acetaminophen glucuronide, and p‐anisic acid) with CV183 > 0.3, for which metabolomics studies have been scarce, are considered highly variable here. We identified 30 age‐related metabolites, 18 BMI‐related metabolites, and 42 sex‐related metabolites. Among the identified metabolites, three metabolites were found to be associated with all three physiological parameters (age, BMI, and sex), which included dehydroepiandrosterone sulfate, 3‐methylcrotonylglycine and N‐acetyl‐aspartic acid. Pearson's coefficients demonstrated that some age‐, BMI‐, and sex‐related compounds are strongly correlated, suggesting that age, BMI, and sex could affect them concomitantly. Conclusion Metabolic differences between distinct physiological statuses were found to be related to several metabolic pathways (such as the caffeine metabolism, the amino acid metabolism, and the carbohydrate metabolism), and these findings may be key for the discovery of new diagnostics and treatments as well as new understandings on the mechanisms of some related diseases.
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