Neuroprotective Effect of Hyperbaric Oxygen Therapy on Anterior Ischemic Optic Neuropathy

The study investigated the therapeutic effect of hyperbaric oxygen (HBO) on anterior ischemic optic neuropathy in a rodent model (rAION). rAION was laser-induced in one eye of 63 mice. The fellow (uninjured) eye served as an internal control. Thirty-three mice underwent two 90-min sessions of 100% oxygen (2 atm) treatment immediately following injury and one session daily thereafter for up to 14 days. The remaining mice were untreated. Retinas were harvested at different time points, and mRNA levels of various genes were analyzed by real-time polymerase chain reaction and histologic study. Untreated mice: day 1 post-rAION – SOD-1 (oxidative-stress-related) decreased to 82% of control (uninjured eye) levels (P < 0.05), Caspase-3 (proapoptotic) decreased to 89%, Bcl-xL mildly increased (117%; all NS); day 3 – HO-1 and endothelial nitric oxide synthase (eNOS; ischaemia-related) decreased to 74%, and Bcl-2-associated X protein, Caspase-3, and B-cell lymphoma 2 (Bcl-2; apoptotic) increased by 170, 120, and 111%, respectively (all NS); day 21 – HO-1 increased to 222% (NS) and eNOS decreased to 48% (P < 0.05). Treated mice: day 1 – SOD-1 and Caspase-3 remained unchanged, Bcl-2 and Bcl-xL mildly increased (112 and 126% respectively); day 3 – HO-1 and eNOS increased, apoptosis-related gene decreased; day 21 – SOD-1 decreased whereas eNOS increased (P < 0.05), and HO-1 increased to a lesser degree than without treatment. None of the oxygen-treated animals had retinal ganglion cell loss or a decrease in Thy-1 expression. In conclusion, HBO treatment after rAION induction influences the expression of apoptosis-related genes as well as oxidative-stress-induced and ischaemia-related genes and may exert a neuroprotective effect

The Youngest Victims: Children and Youth Affected by War

In 1989, the United Nation Convention on the Rights of the Child declared, “[state parties] shall take all feasible measures to ensure protection and care of children who are affected by an armed conflict.” In addition to attempting to secure the welfare of children in armed conflict, the Convention went on to ban the recruitment and deployment of children during armed conflict. Despite the vast majority of sovereign nations signing and ratifying this agreement, this treaty, unfortunately, has not prevented children and youth from witnessing, becoming victims of, or participating in political, ethnic, religious, and cultural violence across the past three decades. This chapter offers an “ecological perspective” on the psychosocial consequences of exposure to the trauma of war-related violence and social disruption

Regulation of lipid droplet size in mammary epithelial cells by remodeling of membrane lipid composition-a potential mechanism.

Milk fat globule size is determined by the size of its precursors-intracellular lipid droplets-and is tightly associated with its composition. We examined the relationship between phospholipid composition of mammary epithelial cells and the size of both intracellular and secreted milk fat globules. Primary culture of mammary epithelial cells was cultured in medium without free fatty acids (control) or with 0.1 mM free capric, palmitic or oleic acid for 24 h. The amount and composition of the cellular lipids and the size of the lipid droplets were determined in the cells and medium. Mitochondrial quantity and expression levels of genes associated with mitochondrial biogenesis and polar lipid composition were determined. Cells cultured with oleic and palmitic acids contained similar quantities of triglycerides, 3.1- and 3.8-fold higher than in controls, respectively (P < 0.0001). When cultured with oleic acid, 22% of the cells contained large lipid droplets (>3 μm) and phosphatidylethanolamine concentration was higher by 23 and 63% compared with that in the control and palmitic acid treatments, respectively (P < 0.0001). In the presence of palmitic acid, only 4% of the cells contained large lipid droplets and the membrane phosphatidylcholine concentration was 22% and 16% higher than that in the control and oleic acid treatments, respectively (P < 0.0001). In the oleic acid treatment, approximately 40% of the lipid droplets were larger than 5 μm whereas in that of the palmitic acid treatment, only 16% of the droplets were in this size range. Triglyceride secretion in the oleic acid treatment was 2- and 12-fold higher compared with that in the palmitic acid and control treatments, respectively. Results imply that membrane composition of bovine mammary epithelial cells plays a role in controlling intracellular and secreted lipid droplets size, and that this process is not associated with cellular triglyceride content

Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN

Tumor macrophages are generally considered to be alternatively/M2 activated to induce secretion of pro-angiogenic factors such as VEGF and MMPs. EMMPRIN (CD147, basigin) is overexpressed in many tumor types, and has been shown to induce fibroblasts and endothelial cell expression of MMPs and VEGF. We first show that tumor cell interactions with macrophages resulted in increased expression of EMMPRIN and induction of MMP-9 and VEGF. Human A498 renal carcinoma or MCF-7 breast carcinoma cell lines were co-cultured with the U937 monocytic-like cell line in the presence of TNFalpha (1 ng/ml). Membranal EMMPRIN expression was increased in the co-cultures (by 3-4 folds, p&lt;0.01), as was the secretion of MMP-9 and VEGF (by 2-5 folds for both MMP-9 and VEGF, p&lt;0.01), relative to the single cultures with TNFalpha. Investigating the regulatory mechanisms, we show that EMMPRIN was post-translationally regulated by miR-146a, as no change was observed in the tumoral expression of EMMPRIN mRNA during co-culture, expression of miR-146a was increased and its neutralization by its antagomir inhibited EMMPRIN expression. The secretion of EMMPRIN was also enhanced (by 2-3 folds, p&lt;0.05, only in the A498 co-culture) via shedding off of the membranal protein by a serine protease that is yet to be identified, as demonstrated by the use of wide range protease inhibitors. Finally, soluble EMMPRIN enhanced monocytic secretion of MMP-9 and VEGF, as inhibition of its expression levels by neutralizing anti-EMMPRIN or siRNA in the tumor cells lead to subsequent decreased induction of these two pro-angiogenic proteins. These results reveal a mechanism whereby tumor cell-macrophage interactions promote angiogenesis via an EMMPRIN-mediated pathway

Milk fat content and DGAT1 genotype determine lipid composition of the milk fat globule membrane.

During secretion of milk fat globules, triacylglycerol (TAG) droplets are enveloped by a phospholipid (PL) trilayer. Globule size has been found to be related to polar lipid composition and fat content, and milk fat content and fatty acid composition have been associated with the diacylglycerol acyltransferase 1 (DGAT1) K232A polymorphism; however, the association between the DGAT1 polymorphism and fat globule size and polar lipid composition has not been studied. The ratio between polar and neutral lipids as well as the composition of the polar lipids in milk has industrial as well as nutritional and health implications. Understanding phenotypic and genotypic factors influencing these parameters could contribute to improving milk lipid composition for dairy products. The focus of the present study was to determine the effect of both fat content and DGAT1 polymorphism on PL/TAG ratio, as a marker for milk fat globule size, and detailed PL composition. Milk samples were selected from 200 cows such that there were equal numbers of samples for the different fat contents as well as per DGAT1 genotype. Samples were analyzed for neutral and polar lipid concentration and composition. PL/TAG ratio was significantly associated with both fat content and DGAT1 genotype. Phosphatidylinositol and phosphatidylserine concentrations were associated with fat content*DGAT1 genotype with a stronger association for the AA than the KK genotype. Sphingomyelin concentration tended to interact with fat content*DGAT1 genotype. Phosphatidylethanolamine (PE) concentration showed a biphasic response to fat content, suggesting that multiple biological processes influence its concentration. These results provide a new direction for controlling polar lipid concentration and composition in milk through selective breeding of cows

Transcription levels of activity markers of mitochondria and phospholipid converting enzyme are modulated by free fatty acids (FFAs).

<p>Mammary epithelial cells were treated with 100 μM FFA (capric, palmitic or oleic acid) or with FFA-free medium (control) for 2 h; RNA was extracted and gene-expression levels of (A) PGC-1α, (B) PGC-1β, (C) NDUFAF3 and (D) PEMT were analyzed by real-time PCR. All data are presented as mean ± SEM of the expression level of the assayed gene normalized to the geometric mean of two housekeeping genes. Different letters indicate significant differences between treatment groups (<i>P</i> < 0.05).</p

Triglyceride (Tg) secretion from mammary epithelial cells is altered in the presence of specific free fatty acids (FFAs).

<p>Mammary epithelial cells were treated with 100 μM FFA (palmitic or oleic acid) or with FFA-free medium (control) for 24 h, then the medium was collected and Tg content was determined. Data are presented as mean ± SEM. Different letters indicate significant differences between treatment groups (<i>P</i> < 0.05).</p

Primer Sequences Used for Real-Time PCR Analysis.

<p>Primer Sequences Used for Real-Time PCR Analysis.</p

Specific free fatty acids (FFA) influence the amount and composition of phospholipid in mammary epithelial cells.

<p>Mammary epithelial cells were treated with 100 μM FFA (capric, palmitic or oleic acid) or with FFA-free medium (control) for 24 h; lipids were extracted and analyzed by HPLC-ELSD. (A) Membrane lipid amounts. (B) Phospholipid weight %. The percent of the amount of an individual phospholipid out of the summed phospholipids amounts. (C) Weight ratio between phosphatidylcholine and phosphatidylethanolamine. All data are presented as mean ± SEM. Different letters indicate significant differences between treatment groups (<i>P</i> < 0.05). PI: phosphatidylinositol; PE: phosphotidylethanolamine; PS: phosphatidylserine; PC: phosphotidylcholine; SM: sphingomyelin.</p