Slothorr3154

The risk of tuberculosis (TB) disease is increased in children with chronic kidney disease (CKD), even higher in stage 5 CKD/kidney failure and especially high after kidney transplantation due to immunosuppression. TB disease may follow recent primary infection, or result from reactivation of latent infection. Reactivation is more common in adults, while progression following primary infection makes up a greater proportion of disease in children. Recommendations for preventing TB disease in some low TB incidence countries have previously included offering Bacillus Calmette-Guérin (BCG) vaccine to all children listed for kidney transplant if they had not received this as part of previous national immunisation programmes. Based on the available evidence, we recommend modifying this practice, focusing instead on awareness of risk factors for TB exposure, infection and disease and the use of appropriate testing strategies to identify and treat TB infection and disease.

A close relationship between sagittal spinal alignment and hip osteoarthritis (OA) has been documented. This study aimed to examine the relationship between hip joint proximity area and sagittal balance parameters in healthy subjects.

This prospective study enrolled 47 healthy volunteers who underwent 320-detector row upright computed tomography. Acquired data were reconstructed in a virtual three-dimensional space. The proximity area was determined by < 1mm of the Hausdorff distance between the acetabulum and the femoral head. Volunteers were divided into the anterior and posterior proximity groups depending on the position of the closest area. Sagittal balance parameters [sagittal vertical axis (SVA), T1 spinopelvic inclination (T1-SPi), T1-pelvic angle, pelvic tilt, sacral slope, pelvic incidence, lumbar lordosis, thoracic kyphosis), offset distance between the centre of the acoustic meati (CAM) and C7 plumb line (CAM-C7-offset), and offset distance between the CAM and hip axis (HA) (CAM-HA-offset)] were compared between the two groups using independent sample t test.

The anterior proximity group (n = 24) had higher SVA (p = 0.016) and T1-Spi (p = 0.015) than the posterior proximity group (n = 23). CAM-HA-offset was higher in the posterior than in the anterior proximity group (p < 0.000). There was no difference in other parameters (p > 0.05).

The anterior proximity group had a positive anterior spinal balance; the posterior proximity group may have a more posterior gravity line than the hip joint centre. The anterior spinal balance may contribute to the anterior loading of the hip joint, with known relation with the initiation and onset of hip OA.

The anterior proximity group had a positive anterior spinal balance; the posterior proximity group may have a more posterior gravity line than the hip joint centre. The anterior spinal balance may contribute to the anterior loading of the hip joint, with known relation with the initiation and onset of hip OA.Vascular smooth muscle cell (VSMC) phenotypic switching is a hallmark of vascular remodeling that contributes to atherosclerotic diseases. MicroRNA 4463 (miR-4463) has been implicated in the development of arteriosclerosis obliterans, whereas the underlying mechanisms in VSMCs have not been fully addressed. In this study, we assessed whether miR-4463 is involved in the phenotypic switching process in VSMCs. Oxidized low-density lipoprotein (Ox-LDL, 50 mg/L) was used to simulate the oxidative stress condition, and miR-4463 expression in VSMCs was detected by a quantitative polymerase chain reaction. To determine the effect of Ox-LDL-mediated regulation of miR-4463 on the phenotypic switching of VSMCs, cell counting kit-8, cell migration assays, and cytoskeleton test were performed. After using specific antagonists of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK), the relationship between miR-4463 and its downstream signaling proteins was explored. Ox-LDL induced oxidative stress to promote VSMC transformation from contraction to secretion, which clearly decreased the level of miR-4463. Then, downregulated miR-4463 enhanced the migration and phenotypic transformation of VSMCs and activated the phosphorylation of JNK and ERK; these effects were increased after Ox-LDL induction. As expected, inhibiting the two signaling proteins blocked the effect of the miR-4463 inhibitor combined with Ox-LDL. In addition, inhibition of miR-4463 led to the upregulation of basic fibroblast growth factor (bFGF) expression. The results of this study demonstrate that miR-4463 is a novel regulator of VSMC function in hypoxic conditions and modulates VSMC phenotypic switching via the JNK and ERK signaling pathways; bFGF may be the target gene of miR-4463.Bile salt-dependent lipase (BSDL) within intestinal lumen can be endocytosed by enterocytes and support the intestinal barrier function. However, the epithelial-supporting effect of this protein has not been verified in a human cell line and neither the direct signaling pathway nor the function of endocytosis in this process has been clearly identified. We sought to investigate the signaling pathway and the membrane receptor through which BSDL might exert these effects using intestinal epithelial cells. Caco-2 cells were treated with recombinant BSDL, and the barrier function, cell proliferation, and activation of the Wnt signaling pathway were assessed. The effect of Wnt signaling activation induced by BSDL and BSDL endocytosis was investigated in LRP6-silenced and non-silenced cells. Moreover, caveolae- and clathrin-dependent endocytosis inhibitors were also applied respectively to analyze their effects on Wnt signaling activation induced by BSDL. BSDL treatment increased the barrier function but not proliferation of Caco-2 cells. NSC 309132 molecular weight It also induced β-catenin nuclear translocation and activated Wnt target gene transcription. Moreover, in the Wnt pathway, BSDL increased the levels of non-phosphorylated-β-catenin (Ser33/37/Thr41) and phosphorylated-β-catenin (Ser552). Notably, the silencing of LRP6 expression impaired BSDL endocytosis and decreased BSDL-induced β-catenin nuclear translocation. The inhibition of BSDL endocytosis induced by caveolae-mediated endocytosis inhibitor was stronger than that by clathrin-mediated endocytosis inhibitor, and the Wnt signaling activation associated with its endocytosis was also most likely caveolae-dependent. Our findings suggested that LRP6, a canonical Wnt pathway co-receptor, can mediate BSDL endocytosis and then activate Wnt signaling in Caco-2 cells.