Citations

An all-in-one Circulating Tumor Cell (CTC) isolation platform with streamlined multiplex integration of proteomic and genomic clinical testing.

Abstract BACKGROUND Revascularization of a stenotic renal artery improves kidney function only in select patients with renovascular hypertension (HT) secondary to atherosclerosis. However, the effects of reversal of renovascular HT (RRHT) on the nonstenotic kidney are unclear. We hypothesized that concurrent hypercholesterolemia (HC) attenuates nonstenotic kidney recovery. METHODS Female domestic pigs were randomized as Normal, renovascular HT, HT+RRHT, HTC (renovascular HT and HC), and HTC+RHT ( n = 7 each). RRHT or sham was performed after 6 weeks of HT. Nonstenotic renal blood flow, glomerular filtration rate, and injurious pathways were studied 4 weeks later. RESULTS Mean arterial pressure increased similarly in HT and HTC and decreased after RRHT. Oxidative stress increased in HT and HTC kidneys, and decreased in HT+RRHT, but remained elevated in HTC+RRHT. Renal interstitial fibrosis, glomerulosclerosis, and tubular injury were all attenuated in HT+RRHT, but not HTC+RRHT. Endothelin-1 signaling and PGF2α isoprostane levels were elevated in both HTC and HTC+RRHT pigs. CONCLUSIONS RRHT reverses nonstenotic kidney injury in experimental renovascular HT, but concurrent HC blunts regression of kidney injury, possibly due to predominant vasoconstrictors and oxidative stress. These findings reinforce the contribution of the nonstenotic kidney and of prevailing cardiovascular risk factors to irreversibility of kidney dysfunction after revascularization.

Significance Skeletal muscle is increasingly recognized as a secretory organ. Revealing the identity and function of myokines can improve our understanding of skeletal muscle function under sedentary or exercise conditions, as well as its coordination with other organs, tissues, and overall body metabolism. This study identifies musclin as an exercise-responsive myokine critical for skeletal muscle adaptation to physical activity. We develop a musclin-encoding gene ( Ostn ) knockout mouse, which allows us to determine a previously unrecognized physiologic function of musclin in regulation of skeletal muscle mitochondrial biogenesis and physical endurance. The demonstrated molecular mechanism for musclin-dependent skeletal muscle adaptation to exercise also transforms the perspective on natriuretic peptide signaling, particularly as it relates to physical activity and exercise-induced remodeling in different tissues.

BACKGROUNDThe objective of this study was to demonstrate that computer‐extracted image phenotypes (CEIPs) of biopsy‐proven breast cancer on magnetic resonance imaging (MRI) can accurately predict pathologic stage.METHODSThe authors used a data set of deidentified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. In total, 91 biopsy‐proven breast cancers were analyzed from patients who had information available on pathologic stage (stage I, n = 22; stage II, n = 58; stage III, n = 11) and surgically verified lymph node status (negative lymph nodes, n = 46; ≥ 1 positive lymph node, n = 44; no lymph nodes examined, n = 1). Tumors were characterized according to 1) radiologist‐measured size and 2) CEIP. Then, models were built that combined 2 CEIPs to predict tumor pathologic stage and lymph node involvement, and the models were evaluated in a leave‐1‐out, cross‐validation analysis with the area under the receiver operating characteristic curve (AUC) as the value of interest.RESULTSTumor size was the most powerful predictor of pathologic stage, but CEIPs that captured biologic behavior also emerged as predictive (eg, stage I and II vs stage III demonstrated an AUC of 0.83). No size measure was successful in the prediction of positive lymph nodes, but adding a CEIP that described tumor “homogeneity” significantly improved discrimination (AUC = 0.62; P = .003) compared with chance.CONCLUSIONSThe current results indicate that MRI phenotypes have promise for predicting breast cancer pathologic stage and lymph node status. Cancer 2016;122:748–757. © 2015 American Cancer Society.

Age is the major risk factor for developing Alzheimer’s disease (AD), and modifying age-related factors may help to delay the onset of the disease. The goal of this study was to investigate the relationship between age and the metabolic factors related to the risk of developing AD. The concentrations of insulin, amylin, and amyloid-β peptide (Aβ) in plasma were measured. We further measured the activity of serum Aβ degradation by using fluorescein- and biotin-labeled Aβ40. Apolipoprotein E4 allele (ApoE4) and cognitive impairment were characterized. Subjects were divided into three age groups: 60–70, 70–80, and ≥80 years old. We found that the older the subjects, the lower the concentration of insulin (p = 0.001) and the higher the concentration of Aβ1-40 (p = 0.004) in plasma. However, age was not associated with the concentration of another pancreatic peptide, amylin, and only marginally with Aβ1-42. These relationships remained in the absence of diabetes, cardiovascular disease, and stroke, and regardless of the presence of ApoE4 and cognitive impairment. Both age and ApoE4 were inversely associated with, while insulin was positively associated with, the activities of Aβ degradation in serum. Our study suggested that low concentration of insulin and high concentration of Aβ40 are aging factors related to the risk of AD.