Vascular endothelial growth factor receptor-2 (VEGFR-2) activation by VEGF-A is essential in vasculogenesis and angiogenesis. We have generated a pan-phosphorylation site map of VEGFR-2 and identified one major tyrosine phosphorylation site in the kinase insert (Y951), in addition to two major sites in the C-terminal tail (Y1175 and Y1214). In developing vessels, phosphorylation of Y1175 and Y1214 was detected in all VEGFR-2-expressing endothelial cells, whereas phosphorylation of Y951 was identified in a subset of vessels. Phosphorylated Y951 bound the T-cell-specific adapter (TSAd), which was expressed in tumor vessels. Mutation of Y951 to F and introduction of phosphorylated Y951 peptide or TSAd siRNA into endothelial cells blocked VEGF-A-induced actin stress fibers and migration, but not mitogenesis. Tumor vascularization and growth was reduced in TSAd-deficient mice, indicating a critical role of Y951-TSAd signaling in pathological angiogenesis

Background/Aims: Contrast-induced nephropathy (CIN) is at present the third leading cause of hospital-acquired acute kidney injury (AKI). Traditionally, it is diagnosed by measuring the increase of the serum creatinine concentration. However, in patients with acute changes in their glomerular filtration rate, serum creatinine is an insensitive marker. This clinical study was designed to investigate whether human urinary interleukin-18 (IL-18) and neutrophil gelatinase-associated lipocalin (NGAL) are early predictive markers for AKI after coronary angiography and their correlation with later cardiac events. Methods: Patients undergoing coronary angiography using low-osmolar contrast medium were enrolled and then followed up for at least 17 months. Urine samples were collected before and 24 h after coronary angiography and IL-18 and NGAL levels measured by using an ELISA kit. Results: CIN was diagnosed in 13 of 150 (8.7%) patients (CIN group); 27 patients without CIN served as control group. At 24 h after the procedure, the urinary IL-18 and NGAL levels were significantly increased in the CIN group, but not in the control group (p < 0.05). The predictable time of AKI onset determined by IL-18 was 24 h earlier than determined by serum creatinine (p < 0.01). Receiver operating characteristic curve analysis showed that both IL-18 and NGAL showed a good performance in early diagnosis of CIN as compared with serum creatinine (p < 0.05). We also found that IL-18 is an independent predictive marker for later major cardiac events: relative risk = 2.09 (p < 0.01). Conclusions: We conclude that urinary IL-18 or NGAL could be early biomarkers of CIN and that urinary IL-18 is well associated with the later cardiac outcomes in patients after coronary angiography.

We evaluated the use of blood serum N-glycan fingerprinting as a tool for the diagnosis of hepatocellular carcinoma (HCC) in patients with cirrhosis induced by hepatitis B virus (HBV). A group of 450 HBV-infected patients with liver fibrosis or cirrhosis with or without HCC were studied. HCC was diagnosed by ␣-fetoprotein (AFP) analysis, ultrasonography, and/or computed tomography and was studied histologically. N-glycan profiles of serum proteins were determined with DNA sequencer-based carbohydrate analytical profiling technology. In this study, we found that a branch alpha(1,3)-fucosylated triantennary glycan was more abundant in patients with HCC than in patients with cirrhosis, patients with fibrosis, and healthy blood donors, whereas a bisecting core alpha(1,6)-fucosylated biantennary glycan was elevated in patients with cirrhosis. The concentration of these 2 glycans and the log ratio of peak 9 to peak 7 (renamed the GlycoHCCTest) were associated with the tumor stage. Moreover, for screening patients with HCC from patients with cirrhosis, the overall sensitivity and specificity of the GlycoHCCTest were very similar to those of AFP. Conclusion: This study indicates that a branch alpha(1,3)-fucosylated glycan is associated with the development of HCC. The serum N-glycan profile is a promising noninvasive method for detecting HCC in patients with cirrhosis and could be a valuable supplement to AFP in the diagnosis of HCC in HBV-infected patients with liver cirrhosis. Its use for the screening, follow-up, and management of patients with cirrhosis and HCC should be evaluated further.

Summary The rice–rice blast pathosystem is of great interest, not only because of the damaging potential of rice blast to the rice crop, but also because both the pathogen and its host are experimentally amenable. The rice blast resistance gene Pik, which is one of the five classical alleles located at the Pik locus on the long arm of chromosome 11, confers high and stable resistance to many Chinese rice blast isolates. The isolation and functional characterization of Pik were performed in the present study through genetic and genomic approaches. A combination of Pik‐1 and Pik‐2 is required for the expression of Pik resistance. Both Pik‐1 and Pik‐2 encode coiled‐coil nucleotide binding site leucine‐rich repeat (NBS‐LRR) proteins, and each shares a very high level of protein identity with corresponding proteins encoded by the Pik‐m and Pik‐p alleles. Pik could be distinguished from other Pik alleles, including Pik‐m and Pik‐p, by the allele‐specific, single‐nucleotide polymorphism T1‐2944G. The coupled genes probably did not evolve as a result of a duplication event, and are far from any NBS‐LRR R gene characterized. Pik is a younger allele at the locus that probably emerged after rice domestication.

The radiological assessment of muscle properties—size, mass, density (also termed radiodensity), composition, and adipose tissue infiltration—is fundamental in muscle diseases. More recently, it also became obvious that muscle atrophy, also termed muscle wasting, is caused by or associated with many other diseases or conditions, such as inactivity, malnutrition, chronic obstructive pulmonary disorder, cancer-associated cachexia, diabetes, renal and cardiac failure, and sarcopenia and even potentially with osteoporotic hip fracture. Several techniques have been developed to quantify muscle morphology and function. This review is dedicated to quantitative computed tomography (CT) of skeletal muscle and only includes a brief comparison with magnetic resonance imaging. Strengths and limitations of CT techniques are discussed in detail, including CT scanner calibration, acquisition and reconstruction protocols, and the various quantitative parameters that can be measured with CT, starting from simple volume measures to advanced parameters describing the adipose tissue distribution within muscle. Finally, the use of CT in sarcopenia and cachexia and the relevance of muscle parameters for the assessment of osteoporotic fracture illustrate the application of CT in two emerging areas of medical interest.

B7-H3 is a member of the B7-family of co-stimulatory molecules, which has been shown to be broadly expressed in various tumor tissues, and which plays an important role in adaptive immune responses. The role of B7-H3 in osteosarcoma, however, remains unknown. In this study we used immunohistochemistry to analyze B7-H3 expression in 61 primary osteosarcoma tissues with case-matched adjacent normal tissues, and 37 osteochondroma and 20 bone fibrous dysplasia tissues. B7-H3 expression was expressed in 91.8% (56/61) of the osteosarcoma lesions, and the intensity of B7-H3 expression in osteosarcoma was significantly increased compared with adjacent normal tissues, osteochondroma and bone fibrous dysplasia tissues (p<0.001). Patients with high tumor B7-H3 levels had a significantly shorter survival time and recurrence time than patients with low tumor B7-H3 levels (p<0.001). Moreover, tumor B7-H3 expression inversely correlated with the number of tumor-infiltrating CD8+ T cells (p<0.05). In vitro, increasing expression of B7-H3 promotes osteosarcoma cell invasion, at least in part by upregulating matrix metalloproteinase-2 (MMP-2). In conclusion, our study provides the first evidence of B7-H3 expression in osteosarcoma cells as a potential mechanism controlling tumor immunity and invasive malignancy, and which is correlated with patients’ survival and metastasis.

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