Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Multicenter Study
Indoleamine 2,3 dioxygenase, age, and immune activation in people living with HIV.
Immune activation complicates HIV despite antiretroviral therapy (ART). Indoleamine 2,3 dioxygenase (IDO) catabolizes tryptophan (T) to kynurenine (K), regulating immune activity, and IDO activity increases with age. This study examines the relationship of IDO activity, bacterial translocation, and aging in people living with HIV (PLWH) on ART. ⋯ K:T and neopterin were associated. PLWH had elevated IDO activity, at younger ages, despite ART. This study suggests K:T ratio increases with age in both groups and is elevated in PLWH at all ages compared with age-matched controls.
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This study aimed to assess the diagnostic value of two serum angiogenetic markers neuropilin-1 (NRP-1) and angiopoietin-2 (ANG-2) in patients with hepatocellular carcinoma (HCC) and their relation to tumor characteristics. 149 subjects were recruited and divided into 50 patients with recently diagnosed HCC, 49 patients with cirrhosis on top of hepatitis C virus infection, and 50 healthy subjects. Serum NRP-1 and ANG-2 were estimated by ELISA. Alpha-fetoprotein (AFP) levels were measured using fluorescence immunoassay. ⋯ In conclusion, NRP-1 is a potential serological marker for HCC diagnosis and is better than ANG-2. It is feasible to be estimated in combination with AFP to enhance its diagnostic power. High serum NRP-1 and ANG-2 levels are associated with advanced HCC tumor characteristics.
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This study aimed to assess the diagnostic value of serum and urinary netrin-1 in patients with type 2 diabetes mellitus (T2DM) at different stages of diabetic nephropathy (DN) and to compare its efficacy of estimation in serum with that in the urine. This study was carried out on 135 patients with T2DM and 45 healthy subjects. The patients with diabetes were divided according to urinary albumin creatinine ratio (UACR) into: T2DM with normoalbuminuria, incipient DN with microalbuminuria, and overt DN with macroalbuminuria groups. ⋯ In T2DM groups, the urinary and serum netrin-1 correlated with each other and were independently related to fasting blood glucose, UACR, and estimated glomerular filtration rate. Receiver operating characteristic curve analysis showed that the area under the curve of urinary netrin-1 was 0.916 which is significantly higher than that of serum netrin-1 (0.812) for the detection of incipient DN and reached 0.938 on coestimation of both urinary and serum netrin-1. In conclusion, netrin-1 is a potential diagnostic marker for early detection of DN with its estimation in urine has higher accuracy than that of serum.
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Chronic kidney disease (CKD) is significantly associated with peripheral arterial disease (PAD) in some studies, but data on the association of the risk of PAD across a broad range of kidney function in patients with type 2 diabetes are limited. Between October 17, 2013 and February 7, 2015, all consecutive outpatients with type 2 diabetes underwent ankle-brachial index (ABI) examination. We investigated the association of estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR) with the risk of PAD. ⋯ Similarly, within each eGFR group, a higher ACR category was also associated with PAD. The OR for PAD was highest in patients with eGFR <30 mL/min/1.73 m2 and macroalbuminuria (OR 14.42, 95% CI 4.60 to 45.31) when compared with the reference group of subjects with eGFR ≥90 mL/min/1.73 m2 and normoalbuminuria. Our study found that cross-classification of eGFR with ACR revealed a more comprehensive association with risk of PAD than eGFR or ACR alone.
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This study investigated the influences of EphA10 and Gli3 on breast cancer (BC) cell proliferation, invasion and migration. Immunohistochemistry was used to reveal the expressions of EphA10 and Gli3 in 18 intraductal carcinomas, 124 invasive carcinomas, 50 paracancerous tissues (2 cm away from the tumor, when possible or available), 50 lobular hyperplastic tissues and 30 normal breast tissues. qRT-PCR and Western blotting were applied to detect the expressions of EphA10 and Gli3 in invasive BC cells (MDA-MB-231, BT20 and Hs578T) and normal human mammary epithelial cells (MCF10A). MDA-MB-231 and BT20 cells were transfected with sh-EphA10, sh-Gli3 or sh-EphA10+sh-Gli3. ⋯ Knockdown of EphA10 or Gli3 suppressed activities of BC cells. Knockdown of both EphA10 and Gli3 was more effective than knockdown of Gli3 alone. Taken together, coexpression of EphA10 and Gli3 promotes BC cell proliferation, invasion and migration.