MicroRNAs (miRNAs) are small noncoding RNAs that play critical roles in regulating various cellular functions by transcriptional silencing. miRNAs can function as either oncogenes or tumor suppressors (oncomirs), depending on cancer types. In our study, using miRNA microarray, we observed that downregulation of the Notch-1 pathway, by delta-tocotrienol, correlated with upregulation of miR-34a, in nonsmall cell lung cancer cells (NSCLC). Moreover, re-expression of miR-34a by transfection in NSCLC cells resulted in inhibition of cell growth and invasiveness, induction of apoptosis and enhanced p53 activity. Furthermore, cellular mechanism studies revealed that induction of miR-34a decreased the expression of Notch-1 and its downstream targets including Hes-1, Cyclin D1, Survivin and Bcl-2. Our findings suggest that delta-tocotrienol is a nontoxic activator of mir-34a which can inhibit NSCLC cell proliferation, induce apoptosis and inhibit invasion, and thus offering a potential starting point for the design of novel anticancer agents.

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A recent and major scientific achievement in the field of biotechnology is the discovery of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats). CRISPR has become one of the most modern and popular tools, mainly due to its low cost and efficiency, which could be used to edit the genome. As a result, this technology holds key to almost every dimension of biomedical and agricultural sciences, and has potential applications in the treatment of viral infections, hemophilia, cancer and inherited genetic anomalies. However, ethical issues could crop up when this technology for editing genes could be unfairly used to improve biological features, solely for the purpose of aesthetics or to gain advantage over others in the population. This would not only lead to societal discrimination and unrest, but also have the potential to change the course of evolution in living beings. In this regard, regulated implementation of the CRISPR technology, risk assessment, policies and procedures should be in place to prevent gross misuse of this technology.

BackgroundPreviously, we reported that ProAlgaZyme (PAZ) and its biologically active fraction improved plasma lipids in hypercholesterolemic hamsters, by significantly increasing the high density lipoprotein cholesterol (HDL-C) while reducing non-HDL cholesterol and the ratio of total cholesterol/HDL-C. Moreover, hepatic mRNA expression of genes involved in HDL/reverse cholesterol transport were significantly increased, while cholesteryl ester transfer protein (CETP) expression was partially inhibited. In the current study, we investigated the therapeutic efficacy of the biologically active fraction of PAZ (BaP) on the plasma lipid and plasma metabolomic profiles in diet induced hypercholesterolemic hamsters.MethodsFifty male Golden Syrian hamsters were fed a high fat diet for 4 weeks prior to randomization into 6 groups, based on the number of days they received subsequent treatment. Thus animals in T0, T3, T7, T10, T14, and T21 groups received BaP for 0, 3, 7, 10, 14, and 21 days, respectively, as their drinking fluid. Plasma lipids were assayed enzymatically, while real-time reverse transcriptase polymerase chain reaction (RT-PCR) provided the transcription levels of the Apolipoprotein (Apo) A1 gene. The plasma metabolomic profile was determined using 1H nuclear magnetic resonance (NMR) spectroscopy in conjunction with multivariate analysis.ResultsPlasma HDL-C was significantly increased in T3 (P < 0.05) and T21 (P < 0.001), while non-HDL cholesterol was significantly reduced in T3, T7, T10 (P < 0.001) and T14, T21 (P < 0.01). Moreover, the ratio of total cholesterol/HDL-C was significantly lower in all BaP treated groups (P < 0.001) as compared with T0. Quantitative RT-PCR showed an increase in Apo A1 expression in T10 (3-fold) and T21 (6-fold) groups. NMR data followed by multivariate analysis showed a clear separation between T0 and T21 groups, indicating a difference in their metabolomic profiles. Plasma concentrations of metabolites associated with a risk for atherosclerosis and cardiovascular disease, including choline, phosphocholine, glycerol-phosphocholine, betaine and carnitine metabolites were significantly lower in the T21 group.ConclusionTreatment with BaP significantly improved the plasma lipid profile by increasing HDL-C and lowering non-HDL cholesterol. In addition, BaP potentially improved the plasma metabolomic profile by reducing the concentration of key metabolites associated with risk for atherosclerosis and cardiovascular disease.

Prognosis of lung cancer, the leading cause of cancer mortality in the US improves if detected at an early stage. Curcumin, a dietary phytochemical has proven anti‐inflammatory, antioxidant, and anti‐carcinogenic activity in several cancer types. This study aims to evaluate the effect of dietary curcumin in lung cancer induced hamster model, using a metabolomics approach. 32 male Golden Syrian hamsters were randomized into treatment (n=20; cancer induced by injecting N‐nitrosobis‐2‐(oxopropyl) amine (BOP);12 weeks), and control (n=12) groups. Each group was subdivided into no (T0, C0) or 2% curcumin (T2, C2) diet groups. Proton nuclear magnetic resonance spectroscopy was conducted on 24h urine samples, in Deuterium oxide using a 700 MHz instrument at 25ºC. The NMR spectra were processed and analyzed using Principal Component Analysis (PCA; SIMCA P+, Umetrics), an unsupervised multivariate analysis technique. The PCA score plots showed clear separation between spectra from(i) the treatment (T0) and control (C0) groups (ii) groups with (T2) and without (T0) dietary curcumin (p < 0.05). The metabolites responsible for the inter‐group differences were quantified using the CHENOMX metabolite database. These metabolites, in addition to providing a mechanistic insight into cancer progression and/or inhibition, may serve as biomarkers for early diagnosis, progression and treatment of lung cancer.