These results together with previous in vitro evidence that AN-PEP efficiently degrades gluten under simulated gastrointestinal conditions warrant confirmation in a larger trial. ACKNOWLEDGMENTS The authors wish to acknowledge Dr. C Gerhardt (DSM Biotechnology Centre) for critical reading of the manuscript. COMMENTS Background The only currently available Tipifarnib myeloid treatment for celiac disease consists of life-long dietary exclusion of gluten, perceived as a substantial burden particularly due to high costs, dietary restriction, reduced social activity, and increased health worries. Alternative treatment modalities that reduce the need of dieting focus on modification of dietary components, enzymatic degradation of gluten, inhibition of intestinal permeability and modulation of the immune response.

Following this, a previous report showed that the gluten-degrading Aspergillus niger-derived prolyl endoprotease (AN-PEP) degraded tox
Obesity-related systemic metabolic dysfunctions such as diabetes mellitus, hypertension, and dyslipidemia are collectively known as metabolic syndrome (Mets) and pose serious health problems throughout the world [1,2]. In addition to the morbidity associated with these metabolic disorders, recent studies have revealed that Mets is linked to an increased risk of cancer in several organ sites including the colorectum [3�C8]. Several pathophysiological mechanisms for this association have been described, including the emergence of insulin resistance, the state of chronic inflammation, induction of oxidative stress, and occurrence of adipokine imbalance [5,6].

In particular, diabetes is closely associated with the development of colorectal cancer (CRC) as obesity is the main determinant of insulin resistance and hyperinsulinemia [7]. Epidemiological studies have also revealed that hypertension may increase the risk of CRC [3,4]. The renin-angiotensin system is a key regulator of cardiovascular function, and its activation is involved in the etiology of Mets, especially hypertension [9]. There is increasing evidence that the renin-angiotensin system may have paracrine and autocrine functions with regard to tissue oxidative stress and chronic inflammation, as well as cellular proliferation and apoptosis [10�C14].

In addition, dysregulation of the renin-angiotensin system has been reported to occur in human malignancies and has been shown to influence cancer cell migration, invasion, and metastasis, all of which are associated with a poor prognosis [10,11,14]. However, the precise mechanisms Anacetrapib by which hypertension plays a role in the early stage of colorectal carcinogenesis remain unclear. The stroke-prone spontaneously hypertensive rat (SHRSP) is a substrain of the spontaneously hypertensive rat (SHR), crossed and further inbred with selected offspring of parents that died of stroke. The SHRSP rats have a higher blood pressure than SHR rats and readily develop apoplexy.