Antihypertensives in Children and Adolescents.

PURPOSE OF REVIEW: To review target organ outcomes and current pharmacologic treatment options for children and adolescents with hypertension. RECENT FINDINGS: There is an increased prevalence of pediatric hypertension. Following the 2017 AAP clinical practice guidelines, there is a growing body of literature illustrating the association between pediatric hypertension and end organ damage, though few studies looking at long-term outcomes. There is also new data to support the use of n-of-1 trials to identify the best antihypertensive therapy for an individual. Pediatric hypertension is increasing in prevalence and is associated with end organ damage. Treatment of hypertensive children has been shown to reverse end organ damage. Due to the lack of large, randomized trials assessing antihypertensive classes against one another, n-of-1 studies may serve as a viable and safe option to optimize patient care.

Noninvasive Staging of Kidney Dysfunction Enabled by Renal-Clearable Luminescent Gold Nanoparticles.

As a "silent killer", kidney disease is often hardly detected at an early stage but can cause lethal kidney failure later on. Thus, a preclinical imaging technique that can readily differentiate between the stages of kidney dysfunction is highly desired for improving our fundamental understanding of kidney disease progression. Herein, we report that in vivo fluorescence imaging, enabled by renal-clearable near-infrared-emitting gold nanoparticles, can noninvasively detect kidney dysfunction, report on the dysfunctional stages, and even reveal adaptive function in a mouse model of unilateral obstructive nephropathy, which cannot be diagnosed with routine kidney function markers. These results demonstrate that low-cost fluorescence kidney functional imaging is highly sensitive and useful for the longitudinal, noninvasive monitoring of kidney dysfunction progression in preclinical research.

Reciprocal regulation of hypoxia-inducible factor 2α and GLI1 expression associated with the radioresistance of renal cell carcinoma.

PURPOSE: Renal cell carcinoma (RCC) is often considered a radioresistant tumor, but the molecular mechanism underlying its radioresistance is poorly understood. This study explored the roles of hypoxia-inducible factor 2α (HIF2α) and sonic hedgehog (SHH)-GLI1 signaling in mediating the radioresistance of RCC cells and to unveil the interaction between these 2 signaling pathways. METHODS AND MATERIALS: The activities of SHH-GLI1 signaling pathway under normoxia and hypoxia in RCC cells were examined by real-time polymerase chain reaction, Western blot, and luciferase reporter assay. The expression of HIF2α and GLI1 in RCC patients was examined by immunohistochemistry, and their correlation was analyzed. Furthermore, RCC cells were treated with HIF2α-specific shRNA (sh-HIF2α), GLI1 inhibitor GANT61, or a combination to determine the effect of ionizing radiation (IR) on RCC cells based on clonogenic assay and double-strand break repair assay. RESULTS: RCC cells exhibited elevated SHH-GLI1 activities under hypoxia, which was mediated by HIF2α. Hypoxia induced GLI1 activation through SMO-independent pathways that could be ablated by PI3K inhibitor or MEK inhibitor. Remarkably, the SHH-GLI1 pathway also upregulated HIF2α expression in normoxia. Apparently, there was a positive correlation between HIF2α and GLI1 expression in RCC patients. The combination of sh-HIF2α and GLI1 inhibitor significantly sensitized RCC cells to IR. CONCLUSIONS: Cross-talk between the HIF2α and SHH-GLI1 pathways was demonstrated in RCC. Cotargeting these 2 pathways, significantly sensitizing RCC cells to IR, provides a novel strategy for RCC treatment.