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音量 5, 問題 3 (2015)

研究論文

Consistency of Metabolite Determination from NMR Spectra over Time and Between Operators

Tso V, Eisner R, Macleod S, Ismond KP, Foshaug RR, Wang H, Joseph R, Chang D, Taylor N and Fedorak RN

With the recent increase in publications of metabolomic-based studies, it is apparent that there are considerable differences in findings between laboratories. Even within a single centre, variability introduced by different highly skilled operators contributing to the same experiment can alter the results. These inconsistencies may contribute to unforeseen experimental confounders and, as such, represent a critical barrier to metabolomics based studies. This issue can impact studies throughout the research spectrum, from basic science to clinical research. One of the potential sources of unforeseen variance in many metabolomic-based studies occurs during the identification and quantification of metabolites. In our study, we examined the profiling consistency of NMR spectra as essential to the interpretation and analysis of metabolite concentrations. This manuscript describes how to evaluate the consistency of metabolite identification and quantification from NMR spectral profiling, between operators and over time, and this methodology can be applied to other quantification techniques in the ‘omics’ realm. We also present the results of our analysis, ranking the urine metabolites’ consistency via NMR quantification. Results from this study will allow metabolomics researchers to better assess consistency and thus ensure that metabolite differences truly reflect biological differences rather than experimental variability.

研究論文

Evaluating the Association of Heme and Heme Metabolites with Lung Cancer Bioenergetics and Progression

Hooda J, Alam MM and Zhang L

Emerging experimental data increasingly show that despite the enhanced glycolytic flux, many types of cancer cells exhibit intensified oxygen consumption or mitochondrial respiration. Even under hypoxia, cancer cells can maintain oxidative phosphorylation at a substantial rate. Heme is a central factor in oxygen utilization and oxidative phosphorylation. It serves as a prosthetic group in many proteins and enzymes involved in mitochondrial respiration. Notably, our recent work showed that non-small-cell lung cancer (NSCLC) cells and xenograft tumors exhibit substantially increased levels of an array of proteins promoting heme synthesis, uptake and function. These proteins include the rate-limiting heme biosynthetic enzyme ALAS, transporter proteins, and various types of oxygen-utilizing hemoproteins such as cytoglobin and cytochromes. In contrast, lowering heme biosynthesis and uptake, like lowering mitochondrial respiration, effectively reduced oxygen consumption, cancer cell proliferation, migration and colony formation. Therefore, elevated heme function and flux are likely key features of NSCLC cells and tumors. Based on this observation, we decided to further ascertain the relationship between heme and lung cancer. We extracted heme and its metabolites from various NSCLC cancer cells and measured the levels of heme in these cells. We also measured the rates of oxygen consumption in
various cancer cells and compared them to the levels of heme in these cells. We expect that these experimental results will enable us to determine the extent to which heme and heme metabolites impact cancer cell bioenergetics and progression.

研究論文

Comparative Phytochemical Profiling of Clerodendrum infortunatum L. Using GC-MS Method Coupled with Multivariate Statistical Approaches

Dey P, Dutta S and Chaudhuri TK

Clerodendrum infortunatum L. is extensively used in traditional and folklore medicine. It has also been recognized in Ayurveda and Unani medicinal systems. Different pharmacological properties of C. infortunatum have already been reported. However, the phytochemical constituents remained unknown. Thus, the present study was performed to investigate and compare the phytochemical composition of the major parts of C. infortunatum using gas chromatographymass spectrometry. GC-MS is one of the most reliable biophysical method for its specificity and repeatability, was utilized for the phytochemical profiling C. infortunatum leaf, stem, root, flower and seed. The phytochemical profiles were further compared using multivariate statistical techniques to evaluate the extent of analogy between the phytochemical profiles. Several bioactive chemical species such as limonene, phytol, catechol, hexadecanoic acid, squalene, dodecanoic acid, vitamin E, hydroxymethylfurfural, stigmasterol, etc. were identified in different parts of C. infortunatum. Derivatives of pharmacological supplements such as cinnamic acid, guaiacol, eugenol, vanillic acid, vitamin D etc. were also detected. Moreover, a wide range of phenolics and phenolic acid derivatives were identified in C. infortunatum, which are known to be primarily responsible for bioactivities of herbal medicines. Principal component analysis coupled with hierarchical clustering revealed the extent of correlation and divergence among the major parts of C. infortunatum in terms of phytochemical fingerprints. Flower, leaf and root demonstrated equivalent phytochemical fingerprints.The results provided insights into the presence of several pharmacologically active constituents. The pattern of phytochemical correlation between leaf, stem, root, flower and seed was established as well.

社説

Anticancer Drug Combinations: A Big Momentum is Needed

Lu DY, Chen EH, Ding J, Xu B and Lu TR

Most cancer therapies are seldom effective by using one anticancer drug owing to refractory and resistance
property of cancer tissues caused by multiple genetic alterations and molecular abnormalities. Despite great popularity of anticancer drug combination utilizations, the hidden rules behind scenarios emerge in new era of anticancer therapy. Most importantly, anticancer drug cocktails need to transform from empirical to science-guided enterprises. This editorial offers the background knowledge of drug combination therapy across the history. Possible future landscapes and drawbacks of current cancer drug combinative therapy are addressed and speculated.

社説

Ebola Origin and Therapies

Lu DY, Che JY, Lu TR and Ding J

Ebola epidemic was re-outbreak again last year. The medical capabilities against disease spreads or therapeutics need to be boosted. Many targeted therapies are still under investigations and newly licensed in a small scale. This article outlines multiple phases of Ebola epidemics-its origin and therapeutic options and economic conditions in these medications. New ideas and future perspectives are given.

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