1.Anthocyanins in cardioprotection: A path through mitochondria.
Liobikas J1, Skemiene K1, Trumbeckaite S1, Borutaite V2. Pharmacol Res. 2016 Mar 30. pii: S1043-6618(16)30118-9. doi: 10.1016/j.phrs.2016.03.036. [Epub ahead of print]
Constantly growing experimental data from in vitro, in vivo and epidemiological studies show the great potential of anthocyanin-containing fruit and berry extracts or pure individual anthocyanins as cardioprotective food components or pharmacological compounds. In general it is regarded that the cardioprotective activity of anthocyanins is related to their antioxidant properties. However there are recent reports that certain anthocyanins may protect the heart against ischemia/reperfusion-induced injury by activating signal transduction pathways and sustaining mitochondrial functions instead of acting solely as antioxidants. In this review, we summarize the proposed mechanisms of direct or indirect actions of anthocyanins within cardiac cells with the special emphasis on recently discovered their pharmacological effects on mitochondria in cardioprotection: reduction of cytosolic cytochrome c preventing apoptosis and sustainment of electron transfer between NADH dehydrogenase and cytochrome c supporting oxidative phosphorylation in ischemia-damaged mitochondria.
2.Identification of bitter compounds in whole wheat bread crumb.
Bin Q1, Peterson DG2. Food Chem. 2016 Jul 15;203:8-15. doi: 10.1016/j.foodchem.2016.01.116. Epub 2016 Jan 28.
Consumer acceptability of whole wheat foods is challenged by negative bitter flavour attributes. In this study, bitter compounds in whole wheat bread crumb were investigated. Utilising sensory-guided multi-dimensional fractionation techniques, the compounds with the highest bitterness intensity in the crumb were purified and identified by LC-MS-ToF and NMR techniques. The main bitter compounds were reported to be L-tryptophan, Wessely-Moser isomers apigenin-6-C-galactoside-8-C-arabinoside & apigenin-6-C-arabinoside-8-C-galactoside, and 9,12,13-trihydroxy-trans-10-octadecenoic acid (pinellic acid). Sensory recombination experiments of the bitter compounds formulated at the concentrations determined in expectorated saliva after bread mastication indicated pinellic acid had the greatest contribution to the bitterness perception of the crumb. Quantitative analysis of pinellic acid in the raw flour was reported to be inherently low compared to bread; the concentration increased more than 30-fold after flour hydration and baking.
3.Enhanced autophagy in cytarabine arabinoside-resistant U937 leukemia cells and its potential as a target for overcoming resistance.
Cheong JW1, Kim Y1, Eom JI2, Jeung HK2, Min YH1. Mol Med Rep. 2016 Apr;13(4):3433-40. doi: 10.3892/mmr.2016.4949. Epub 2016 Feb 29.
Autophagy is a lysosomal degradation mechanism that is essential for cell survival, differentiation, development, and homeostasis. Autophagy protects cells from various stresses, including protecting normal cells from harmful metabolic conditions, and cancer cells from chemotherapeutics. In the current study, a cytarabine arabinoside (Ara‑C)‑sensitive U937 leukemia cell line and an Ara‑C‑resistant U937 (U937/AR) cell line were assessed for baseline autophagy activity by investigating the LC3‑I conversion to LC3‑II, performing EGFP‑LC3 puncta, an acidic autophagolysosome assay, and measuring the expression of various autophagy‑related genes. The results demonstrated significantly higher autophagic activity in the U937/AR cells compared with the U937 cells, when the cells were cultured with or without serum. Furthermore, an increase in the autophagic activity in starved U937/AR cells was demonstrated, compared with that in the starved U937 cells.
4.A phase I study of intermediate dose cytarabine in combination with lenalidomide in relapsed/refractory acute myeloid leukemia.
Griffiths EA1, Brady WE2, Tan W2, Vigil CE3, Thompson JE3, Ford LA4, Dickey NM4, L Bashaw H4, Sperrazza J3, Wetzler M3, Wang ES3. Leuk Res. 2016 Apr;43:44-8. doi: 10.1016/j.leukres.2016.02.003. Epub 2016 Feb 16.
Relapsed/refractory (r/r) Acute Myeloid Leukemia (AML) remains a therapeutic challenge. Cytarabine arabinoside (AraC) forms the backbone of most regimens, with complete responses (CR) ranging from 17 to 20%. Lenalidomide (Len) is approved by the FDA for multiple myeloma and myelodysplasia and has demonstrated activity in AML. We developed a phase I study to evaluate the safety and tolerability of Len in combination with intermediate dose AraC (1.5g/m(2)/day given on days 1-5) in adults with r/r AML. The maximally tolerated dose for this combination was 10mg daily on days 6-26 of a 28day cycle. Dose de-escalation from 25mg was required due to rash, liver function abnormalities, and hypokalemia. Of 32 evaluable patients, five achieved CR (16%), 5CRi (16%) and 3 had hematological improvements for an overall response rate of 41% (13/32). Median overall survival (95% confidence interval) for patients treated on study was 5.8 (2.5-10.6) months and disease free survival was 3.