BackgroundVarious factors impact the severity of malaria, including the nutritional status of the host. Vitamin E, an intra and extracellular anti-oxidant, is one such nutrient whose absence was shown previously to negatively affect Plasmodium development. However, mechanisms of this Plasmodium inhibition, in addition to means by which to exploit this finding as a therapeutic strategy, remain unclear.Methodsα-TTP knockout mice were infected with Plasmodium berghei NK65 or Plasmodium yoelii XL-17, parasitaemia, survival rate were monitored. In one part of the experiments mice were fed with a supplemented diet of vitamin E and then infected. In addition, parasite DNA damage was monitored by means of comet assay and 8-OHdG test. Moreover, infected mice were treated with chloroquine and parasitaemia and survival rate were monitored.ResultsInhibition of α-tocopherol transfer protein (α-TTP), a determinant of vitamin E concentration in circulation, confers resistance to malarial infection as a result of oxidative damage to the parasites. Furthermore, in combination with the anti-malarial drug chloroquine results were even more dramatic.ConclusionConsidering that these knockout mice lack observable negative impacts typical of vitamin E deficiency, these results suggest that inhibition of α-TTP activity in the liver may be a useful strategy in the prevention and treatment of malaria infection. Moreover, a combined strategy of α-TTP inhibition and chloroquine treatment might be effective against drug resistant parasites.
Malaria infection leads to anemia in humans which generally occurs during the chronic phase of the infection. The role that erythropoietic molecules play for anemia during malaria at low parasitemia levels is still controversial due to the lack of suitable animal models which might mimic this condition. In this regard, α-tocopherol transfer protein knockout mice, with undetectable levels of vitamin E in circulation, were possibly used as a model to investigate the role that erythropoietic molecules such as erythropoietin (EPO), erythropoietin receptor (EPOR), and macrophage migration inhibitory factor (MIF) play on the outcome of anemia during uncomplicated malaria infection at low parasitemias. The results indicate that the degree of parasitemia unlikely plays any important effect on mRNA expression of EPO and EPOR in different organs. Moreover, even though EPO and EPOR productions are impaired in the kidney and bone marrow, respectively, other organs such as the liver and spleen intend to compensate production of these cytokines to prevent anemia in the infected animals.
NNMT is a potential biomarker of AdCC.
Abstract. Background Adenoid cystic carcinoma (AdCC) is a rare cancer that arises within the secretory glands, mainly the salivary gland. For head and neck AdCC, the age-adjusted incidence rate is 4.5 cases per 100,000 individuals and exhibits a slight female predominance (1). The risks for delayed recurrence and metastasis in other organs are higher in AdCC than in other oral cancers, such as squamous cell carcinoma (SCC), because of the propensity of AdCC to invade neighbouring tissues and migrate into blood vessels (2, 3). Despite the fact that hundreds of malignant AdCC tumors have been characterized at the molecular level, the underlying regulatory mechanisms of this cancer type remain unclear.To date, many clinical AdCC studies have reported that poor prognosis is associated with pathological features such as AdCC type and grade (4). Histological specimens can be divided into three groups: tubular, cribriform, or solid. Because patients with solid AdCC are especially likely to present with distant metastases, they are the strongest candidates for further surveillance and preventative treatment (5). The use of molecular approaches to elucidate the pathways involved in invasion and migration should significantly add to our understanding of AdCC pathogenesis. Using cell sublines derived from ACCS (an AdCC cell line) by in vivo selection in mice, Ishii et al. (6) demonstrated that interactions between β-catenin and E-cadherin are associated with cell adhesion and lead to tumor metastasis. Further analysis of the molecular mechanisms involved in AdCC should contribute to the identification of potential therapeutic targets.β-catenin is a key molecule in Wnt signalling and plays an important role in cell growth, development, and cancer. The phosphorylation of β-catenin is regulated by several kinases and phosphatases (7). In the absence of extracellular activation, phosphorylated β-catenin is degraded by proteasomes in the cytoplasm. Upon activation of the Wnt signalling pathway, these proteasomes are inhibited, and 53 This article is freely accessible online.
Aldose reductase (AR) is associated with the onset of diabetic complications. Botryllazine A and its analogues were synthesized and evaluated for human AR inhibitory activity. Analogues possessing aromatic bicyclic systems at the C5 position of the central pyrazine ring exhibited superior AR inhibiting activity relative to the parent botryllazine A. In addition, the benzoyl groups at positions C2 and C3 of the pyrazine ring were dispensable for this improved inhibitory activity. Conversely, a benzoyl group-containing phenolic hydroxyl groups-at either position C2 or C3 of the pyrazine ring was essential for attainment of high inhibitory activity approaching that of sorbinil (a highly effective AR inhibitor).
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