Modulation of endoplasmic reticulum stress via sulforaphane-mediated AMPK upregulation against nonalcoholic fatty liver disease in rats

Nonalcoholic fatty liver disease (NAFLD) is a major health concern. Endoplasmic reticulum (ER) stress, inflammation, and metabolic dysfunctions may be targeted to prevent the progress of nonalcoholic fatty liver disease. Sulforaphane (SFN), a sulfur-containing compound that is abundant in broccoli florets, seeds, and sprouts, has been reported to have beneficial effects on attenuating metabolic diseases. In light of this, the present study was designed to elucidate the mechanisms by which SFN ameliorated ER stress, inflammation, lipid metabolism, and insulin resistance — induced by a high-fat diet and ionizing radiation (IR) in rats. In our study, the rats were randomly divided into five groups: control, HFD, HFD + SFN, HFD + IR, and HFD + IR + SFN groups. After the last administration of SFN, liver and blood samples were taken. As a result, the lipid profile, liver enzymes, glucose, insulin, IL-1β, adipokines (leptin and resistin), and PI3K/AKT protein levels, as well as the mRNA gene expression of ER stress markers (IRE-1, sXBP-1, PERK, ATF4, and CHOP), fatty acid synthase (FAS), peroxisome proliferator–activated receptor-α (PPAR-α). Interestingly, SFN treatment modulated the levels of proinflammatory cytokine including IL-1β, metabolic indices (lipid profile, glucose, insulin, and adipokines), and ER stress markers in HFD and HFD + IR groups. SFN also increases the expression of PPAR-α and AMPK genes in the livers of HFD and HFD + IR groups. Meanwhile, the gene expression of FAS and CHOP was significantly attenuated in the SFN-treated groups. Our results clearly show that SFN inhibits liver toxicity induced by HFD and IR by ameliorating the ER stress events in the liver tissue through the upregulation of AMPK and PPAR-α accompanied by downregulation of FAS and CHOP gene expression.     

Apoptosis of antigen-specific T cells induced by oral administration of antigen: comparison of intestinal and non-intestinal immune organs.

Oral administration of a protein without adjuvant brings about oral tolerance (systemic hyporesponsiveness) to that protein by mechanisms such as antigen-induced apoptosis. We monitored the number and apoptosis induction of CD4+ T cells in antigen-specific T cell receptor transgenic mice fed the antigen ovalbumin to identify where events leading to oral tolerance occurred. The antigen was distributed throughout the body, causing apoptosis and a decrease in cell number of CD4+ T cells in most of the lymphoid system: the spleen, peripheral lymph nodes, and the thymus which was not previously reported to be affected. Although apoptosis was induced in the Peyer's patches, the cell number did not change. Unexpectedly, T cells in the mesenteric lymph nodes did not undergo apoptosis; instead, they were more numerous as compared to that in the case of control animals not administered the antigen. The results suggested that the orally administered antigen activated the intestinal immune system, while it induced immune tolerance in other sites.     

Ontogeny of hemopoietic and lymphopoietic tissues in the lizard Chalcides ocellatus (Reptilia,Sauna, Scincidae)

The first and major blood-forming organ to develop in the viviparous lizard Chalcides ocellatus is the yolk sac, which exhibits prominent erythropoietic activity from as early as stage 21 through birth (stage 41). Myeloid cells and megakaryocytes are produced in the yolk sac from stage 23 onward. During lizard embryogenesis hemopoietic activity is also observed in spleen and bone marrow but in neither kidney nor liver. Cells capable of giving rise to lymphocytes both in vivo and in vitro are first found in the thymus at stage 35. Active lymphopolesis in thymus and spleen begins at stages 36 and 39, respectively. In contrast, the gut-associated lymphoid aggregates are not evident before birth.     

Age dependence of the levels of plasma norepinephrine, aldosterone, renin activity and urinary vanillylmandelic acid in normal and essential hypertensives

In the present study the upper reference limits (URLs) for resting plasma norepinephrine, epinephrine, serum aldosterone, plasma renin activity, aldosterone/renin activity ratio, as well as urinary vanillylmandelic acid in healthy Egyptian normotensive subjects over a range of ages (5-60 yr) were established. There was a significant age effect on plasma norepinephrine, UVMA, serum aldosterone and PRA, whereas a single URL for plasma epinephrine level is satisfactory. In uncomplicated untreated essential hypertensive subjects (5-60 yr), the average prevalence of elevation in the plasma norepinephrine, epinephrine and urinary vanillylmandelic acid above their corresponding URLs was 85.10, 62.15 and 83.20%, respectively. This suggests that elevation in plasma catecholamine concentrations is more likely a common consequence than playing a possible role in the pathogenesis of hypertension, supported by insignificant correlation coefficients between the plasma catecholamine levels and resting systolic and diastolic blood pressure values (SBP & DBP) in all hypertensive age groups. Primary hyperaldosteronism was not detected among the normokalemic essential hypertensives at any age using aldosterone/plasma renin activity ratio as a primary screening method. In the present study, 7 statistically significant positive coefficient correlations are reported for SBP or DBP values with UVMA levels in hypertensive children and adolescents, serum aldosterone in old hypertensives, and PRA in adult hypertensives.     

Vitamin D status and vitamin D receptor gene polymorphism in Saudi children with acute lower respiratory tract infection

Molecular Biology Reports - There is a significant association exists between vitamin D deficiencies, low respiratory tract infections, and certain types of VDR gene polymorphism. Various studies...     

The role of circulating tumor cells and K-ras mutations in patients with locally advanced rectal cancer: a prospective study

Molecular Biology Reports - Rectal cancer is a common malignancy with a relatively poor prognosis. We assessed the possible prognostic and predictive role(s) of circulating tumor cells (CTCs) and...