Heat stress elicits different responses in peripheral blood mononuclear cells from Brown Swiss and Holstein cows

This study was undertaken to assess whether peripheral blood mononuclear cells (PBMC) isolated from Brown Swiss (Br) and Holstein (Ho) cows and stimulated with concanavalin A differ in response to chronic exposure to incubation temperatures simulating conditions of hyperthermia. Five multiparous Br and 5 Ho cows were utilized as blood donors. Peripheral blood mononuclear cells were subjected for 65 h to each of 5 treatments (T). Cells were exposed to 39°C continuously (T39) and three 13-h cycles at 40 (T40), 41 (T41), 42 (T42) or 43°C (T43), respectively, which were interspersed with two 13-h cycles at 39°C. Treatment T39 was adopted to mimic normothermia; T40, T41, T42, and T43 mimicked conditions of more severe hyperthermia alternating with normothermia. Measures evaluated at the end of the incubation period were proliferative response (DNA synthesis), intracellular reactive oxygen species (ROS) concentrations, and mRNA abundance of the 72-kDa heat-shock protein (Hsp72). In Br cows, DNA synthesis began to decline when PBMC were repeatedly exposed to 41°C (−22%), whereas DNA synthesis in cells isolated from Ho cows did not begin to decline until 42°C (−40%). Furthermore, under T41 and T42, DNA synthesis from Br cows was lower than in Ho(−24 and −54%, respectively). In both breeds, increased incubation temperatures caused a reduction of intracellular ROS (from −39.6 and −69.7%). Increase in incubation temperatures enhanced Hsp72 mRNA levels only in PBMC isolated from Br cows. The Hsp72 mRNA in Br cows increased significantly under T41 and T43 compared with T39. In both breeds, DNA synthesis was positively and negatively correlated with intracellular ROS and Hsp72 mRNA abundance, respectively (r = 0.85 and r = −0.70, respectively). Results indicated that PBMC from Br cows are less tolerant to chronic heat exposure than those from Ho cows, and that the lower tolerance is associated with higher expression of Hsp72, suggesting that the same level of hyperthermia may be associated with a differential decline of immune function in the 2 breeds.     

Suppression of DNA damage in human peripheral blood lymphocytes by a juice concentrate: A randomized,double‐blind,placebo‐controlled trial

Chronic inflammation contributes to many prevalent diseases worldwide, and it is widely accepted that inflammatory molecules contribute to DNA damage. In this ancillary study, we investigated the influence of an encapsulated fruit and vegetable juice powder concentrate on peripheral blood lymphocytes (PBL) DNA damage. Using a double‐blind, placebo‐controlled approach, subjects were randomly assigned capsules containing placebo, or one of two formulations of the juice powder. Blood was drawn at baseline and after 60 days of capsule consumption. We found DNA damage in isolated PBL is suppressed after consumption of the encapsulated juice powder, and damage was correlated with the level of systemic inflammation. These data suggest a potential health benefit by consuming the juice concentrate capsules through their ability to suppress DNA damage as measured in surrogate tissues (PBL).     

Dietary omega‐3 PUFA and health: Stearidonic acid‐containing seed oils as effective and sustainable alternatives to traditional marine oils

The daily consumption of dietary omega‐3 PUFA is recommended by governmental agencies in several countries and by a number of health organizations. The molecular mechanisms by which these dietary PUFA affect health involve the enrichment of cellular membranes with long‐chain 20‐ and 22‐carbon omega‐3 PUFA that impacts tissues by altering membrane protein functions, cell signaling, and gene expression profiles. These changes are recognized to have health benefits in humans, especially relating to cardiovascular outcomes. Cellular membrane enrichment and health benefits are associated with the consumption of long‐chain omega‐3 PUFA found in marine oils, but are not generally linked with the consumption of alpha‐linolenic acid, the 18‐carbon omega‐3 PUFA found in plant seed oils. However, the supply of omega‐3 PUFA from marine sources is limited and may not be sustainable. New plant‐derived sources of omega‐3 PUFA like stearidonic acid‐soy oil from genetically modified soybeans and Ahiflower oil from Buglossoides arvensis seeds that are enriched in the 18‐carbon omega‐3 PUFA stearidonic acid are being developed and show promise to become effective as well as sustainable sources of omega‐3 PUFA. An example of changes in tissue lipid profiles associated with the consumption of Ahiflower oil is presented in a mouse feeding study.     

Naringenin up‐regulates the expression of death receptor 5 and enhances TRAIL‐induced apoptosis in human lung cancer A549 cells

Scope: While TRAIL is relatively non‐toxic to normal cells, it can selectively induce apoptosis in many types of transformed cells. Nevertheless, some non‐small cell lung cancer (NSCLC) cells are particularly resistant to the effects of TRAIL. Here, we report that in combination with naringenin exposure to TRAIL induced apoptosis in TRAIL‐resistant NSCLC A549 cells with no detectable inhibitory effects on cell proliferation of normal lung fibroblast cells. Methods and results: Cytotoxicity was evaluated by MTT assay. Apoptosis was detected using DAPI staining, and flow cytometry. The protein levels were determined by Western blot analysis. Caspase activity was measured using a colorimetric assay. For knockdown of Bid and DR5 expression, Bid and DR5 siRNAs were transfected into cells via lipofection. We could show that following exposure to naringenin, DR5 proteins were up‐regulated and knockdown of DR5 expression by siRNA attenuated naringenin plus TRAIL‐induced apoptosis. Naringenin and TRAIL effectively induced Bid cleavage and siRNA‐mediated silencing of Bid reduced the sensitizing effect of naringenin. Furthermore, co‐treatment with naringenin and TRAIL resulted in reduction of the clonogenic capacity of A549 cells, and surviving clones could be re‐sensitized for repeated TRAIL treatment. Conclusion: Our results indicate that treatment with a combination of TRAIL and naringenin may be a safe strategy for treatment of resistant NSCLC.