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Tenascin-C is an extracellular matrix glycoprotein implicated in embryogenesis, wound healing and tumor progression. We previously revealed that tenascin-C expression is correlated with the prognosis of patients with glioblastoma. However, the exact role of endogenous tenascin-C in regulation of glioblastoma proliferation and invasion remains to be established. We show here that endogenous tenascin-C facilitates glioblastoma invasion, followed by reactive change of the surrounding brain tissue. Although shRNA-mediated knockdown of endogenous tenascin-C does not affect proliferation of glioblastoma cells, it abolishes cell migration on a two-dimensional substrate and tumor invasion with brain tissue changes in a xenograft model. The tyrosine phosphorylation of focal adhesion kinase, a cytoplasmic tyrosine kinase that associates with integrins, was decreased in tenascin-C-knockdown cells. In the analysis of clinical samples, tenascin-C expression correlates with the volume of peritumoral reactive change detected by magnetic resonance imaging. Interestingly, glioblastoma cells with high tenascin-C expression infiltrate brain tissue in an autocrine manner. Our results suggest that endogenous tenascin-C contributes the invasive nature of glioblastoma and the compositional change of brain tissue, which renders tenascin-C as a prime candidate for anti-invasion therapy for glioblastoma.

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In our study, an increase in ANCA level during remission was associated with a risk of disease relapse. A rise in ANCA level may be useful for guiding treatment decisions in appropriate subsets of patients with ANCA-associated vasculitis.

BackgroundIdiopathic membranous nephropathy (IMN) is increasingly seen in older patients. However, differences in disease presentation and outcomes between older and younger IMN patients remain controversial. We compared patient characteristics between younger and older IMN patients.MethodsWe recruited 171 Japanese patients with IMN, including 90 (52.6%) patients <65 years old, 40 (23.4%) patients 65–70 years, and 41 (24.0%) patients ≥71 years. Clinical characteristics and outcomes were compared between younger and older IMN patients.ResultsDuring a median observation period of 37 months, 103 (60.2%) patients achieved complete proteinuria remission, which was not significantly associated with patient age (P = 0.831). However, 13 (7.6%) patients were hospitalized because of infection. Multivariate Cox proportional hazards models identified older age [adjusted hazard ratio (HR) = 3.11, 95% confidence interval (CI): 1.45–7.49, per 10 years; P = 0.003], prednisolone use (adjusted HR = 11.8, 95% CI: 1.59–242.5; P = 0.014), and cyclosporine used in combination with prednisolone (adjusted HR = 10.3, 95% CI: 1.59–204.4; P = 0.012) as significant predictors of infection. A <25% decrease in proteinuria at 1 month after immunosuppressive therapy initiation also predicted infection (adjusted HR = 6.72, 95% CI: 1.51–37.8; P = 0.012).ConclusionsYounger and older IMN patients had similar renal outcomes. However, older patients were more likely to develop infection when using immunosuppressants. Patients with a poor response in the first month following the initiation of immunosuppressive therapy should be carefully monitored for infection and may require a faster prednisolone taper.

In recent years, milk constituents have become recognized as functional foods, suggesting that their use has a direct and measurable effect on health outcomes. Milk contains two primary sources of protein, the caseins and whey. After processing, the caseins are the proteins responsible for making curds, while whey remains in an aqueous environment. Whey has been touted as a functional food with a number of health benefits.1) The protein fraction in whey comprises four major protein fractions and six minor protein fractions. The major protein fractions in whey are a-lactalbumin (aLA), b-lactoglobulin (bLG), bovine serum albumin, and immunoglobulins. The biological components of whey demonstrate a range of immune-enhancing properties.2) In addition, whey has the ability to act as an antioxidant, 3) antihypertensive, 4) antitumor, 5) hypolipidemic, 1) antiviral, 6) antibacterial, 7) and chelating agent. 8)It is well-known that lactoferrin, the minor component of whey proteins, inhibits production of the inflammatory cytokines tumor necrosis factor (TNF)-a, interleukin (IL)-1b, and IL-6 in monocytes. We have confirmed that lactoferrin protects TNF-a production caused by sensitization of hepatic monocytes (kupffer cells) by lipopolisaccaride.9) It has recently been reported that lactoferrin produces analgesia in the thermal, visceral and formalin-evoked nociceptions in rats.10) However, the efficacy of other proteins has not been clarified with regard to analgesic action.Prostaglandins (PGs) formed by the phospholipase A 2 (PLA 2 ) and cyclooxygenase (COX) enzymes are important mediators of nociception and inflammation.11) On the other hand, emerging information has pointed to the role of another arachidonic acid metabolic pathway (the 5-lipoxygenase (5-LO) pathway) in producing and maintaining inflammation.12) There is evidence that COX-2 and 5-LO are co-expressed and up-regulated in a number of inflammatory diseases and that COX-2 as well as 5-LO inhibitors have beneficial effects in inflammatory diseases. 13)The aim of the present study was to assess three points: 1) Can orally administered aLA potentiate an anti-nociceptive response? 2) Can orally administered aLA potentiate an antiinflammatory response? 3) If so, are COX, PLA 2 , and 5-LO involved in this potentiation by aLA? In this study, we used acetic acid-induced mouse writhing and for pain, carrageenaninduced rat paw edema for acute inflammation, and adjuvantinduced rat arthritis for chronic inflammation. MATERIALS AND METHODS AnimalsMale ICR mouse weighing from 20 to 25 g and male Wistar rats weighing from 150 to 200 g were obtained from SLC Japan, Inc. (Shizuoka, Japan) and housed in plastic cages for 1 week prior to the commencement of experiments under controlled temperature (21Ϯ2°C), humidity (55Ϯ15%), and 12-h light/dark cycle, and the light period was from 7:00 to 19:00. Commercially available rat chow and water were provided ad libitum. This study was performed in accordance with "The guidelines of the Meiji Dairies Corporation for the care and use...

Male Sprague-Dawley rats were underwent superior mesenteric artery occlusion for 45 min followed by reperfusion under urethane anesthesia. Each milk proteins (300 mg/ kg) were injected into the duodenum 1 h before the induction of ischemia. IL-6 release in the blood was measured in course of time. Whey protein isolate (WPI) had the suppressive effect against ischemia/reperfusion-induced IL-6 release, while casein and bovine serum albumin had no effect. Both alpha-lactalbumin (aLA) and beta-lactoglobulin (bLG), major components contained in WPI, significantly inhibited the increase of IL-6. However, aLA had more potent activity compared with bLG. Positive correlation between serum aLA level and efficacy for Ischmia/reperfusion was observed. N(G)-nitro-L-arginine methyl ester, nitric oxide (NO) synthase inhibitor, significantly reversed suppressive effect on IL-6 release by aLA. These findings show that aLA has a marked suppressive effect on pro-inflammatory cytokine release, at least in part, through NO-mediated mechanism.