To elucidate the molecular pathways that modulate renal cyst growth in ADPKD, we performed global gene profiling on cysts of different size (<1 ml, n = 5; 10-20 ml, n = 5; >50 ml, n = 3) and minimally cystic tissue (MCT, n = 5) from five PKD1 human polycystic kidneys using Affymetrix HG-U133 Plus 2.0 arrays. We used gene set enrichment analysis to identify overrepresented signaling pathways and key transcription factors (TFs) between cysts and MCT. We found down-regulation of kidney epithelial restricted genes (e.g. nephron segment-specific markers and cilia-associated cystic genes such as HNF1B, PKHD1, IFT88 and CYS1) in the renal cysts. On the other hand, PKD1 cysts displayed a rich profile of gene sets associated with renal development, mitogen-mediated proliferation, cell cycle progression, epithelial-mesenchymal transition, hypoxia, aging and immune/inflammatory responses. Notably, our data suggest that up-regulation of Wnt/beta-catenin, pleiotropic growth factor/receptor tyrosine kinase (e.g. IGF/IGF1R, FGF/FGFR, EGF/EGFR, VEGF/VEGFR), G-protein-coupled receptor (e.g. PTGER2) signaling was associated with renal cystic growth. By integrating these pathways with a number of dysregulated networks of TFs (e.g. SRF, MYC, E2F1, CREB1, LEF1, TCF7, HNF1B/ HNF1A and HNF4A), our data suggest that epithelial dedifferentiation accompanied by aberrant activation and cross-talk of specific signaling pathways may be required for PKD1 cyst growth and disease progression. Pharmacological modulation of some of these signaling pathways may provide a potential therapeutic strategy for ADPKD.

Many in vitro studies have shown that tea catechins had vevarious health beneficial effects. However, inconsistent results between in vitro and in vivo studies or between laboratory tests and epidemical studies are observed. Low bioavailability of tea catechins was an important factor leading to these inconsistencies. Research advances in bioavailability studies involving absorption and metabolic biotransformation of tea catechins were reviewed in the present paper. Related techniques for improving their bioavailability such as nanostructure-based drug delivery system, molecular modification, and co-administration of catechins with other bioactives were also discussed.

Renal disease variability in autosomal dominant polycystic kidney disease (ADPKD) is strongly influenced by the gene locus (PKD1 versus PKD2). Recent studies identified nontruncating PKD1 mutations in approximately 30% of patients who underwent comprehensive mutation screening, but the clinical significance of these mutations is not well defined. We examined the genotype-renal function correlation in a prospective cohort of 220 unrelated ADPKD families ascertained through probands with serum creatinine #1.4 mg/dl at recruitment. We screened these families for PKD1 and PKD2 mutations and reviewed the clinical outcomes of the probands and affected family members. Height-adjusted total kidney volume (htTKV) was obtained in 161 affected subjects. Multivariate Cox proportional hazard modeling for renal and patient survival was performed in 707 affected probands and family members. Overall, we identified pathogenic mutations in 84.5% of our families, in which the prevalence of PKD1 truncating, PKD1 in-frame insertion/deletion, PKD1 nontruncating, and PKD2 mutations was 38.3%, 4.3%, 27.1%, and 30.3%, respectively. Compared with patients with PKD1 truncating mutations, patients with PKD1 in-frame insertion/deletion, PKD1 nontruncating, or PKD2 mutations have smaller htTKV and reduced risks (hazard ratio Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease worldwide, responsible for 5%-10% of ESRD. 1,2 Mutations in two genes (PKD1 and PKD2) account for most patients with ADPKD. 2,3 Previous studies of European families ascertained through probands enriched with renal failure reported that approximately 85% and approximately 15% of ADPKD families were linked to the PKD1 and PKD2 loci, respectively. 3 However, a higher prevalence of PKD2 of 26% has been recently reported in a population-based study. 4 Disease progression of ADPKD is highly variable, in part because of a strong gene locus effect. [5][6][7][8] Adjusted for age, patients with PKD1 have larger kidneys and earlier onset of ESRD than patients with PKD2 (mean age at ESRD, 53.4 versus 72.7 years old, respectively). 5,6,8 Additionally, significant intrafamilial renal disease variability in ADPKD suggests a modifier effect. [9][10][11] [

It has been an outstanding challenge to achieve implantable energy modules that are mechanically soft (compatible with soft organs and tissues), have compact form factors, and are biodegradable (present for a desired time frame to power biodegradable, implantable medical electronics). Here, we present a fully biodegradable and bioabsorbable high-performance supercapacitor implant, which is lightweight and has a thin structure, mechanical flexibility, tunable degradation duration, and biocompatibility. The supercapacitor with a high areal capacitance (112.5 mF cm−2 at 1 mA cm−2) and energy density (15.64 μWh cm−2) uses two-dimensional, amorphous molybdenum oxide (MoOx) flakes as electrodes, which are grown in situ on water-soluble Mo foil using a green electrochemical strategy. Biodegradation behaviors and biocompatibility of the associated materials and the supercapacitor implant are systematically studied. Demonstrations of a supercapacitor implant that powers several electronic devices and that is completely degraded after implantation and absorbed in rat body shed light on its potential uses.

Abstract. Autosomal dominant polycystic kidney disease (ADPKD) is a common Mendelian disorder that affects approximately 1 in 1000 live births. Mutations of two genes, PKD1 and PKD2, account for the disease in approximately 80 to 85% and 10 to 15% of the cases, respectively. Significant interfamilial and intrafamilial renal disease variability in ADPKD has been well documented. Locus heterogeneity is a major determinant for interfamilial disease variability (i.e., patients from PKD1-linked families have a significantly earlier onset of ESRD compared with patients from PKD2-linked families). More recently, two studies have suggested that allelic heterogeneity might influence renal disease severity. The current study examined the genotype-renal function correlation in 461 affected individuals from 71 ADPKD families with known PKD2 mutations. Fifty different mutations were identified in these families, spanning between exon 1 and 14 of PKD2. Most (94%) of these mutations were predicted to be inactivating. The renal outcomes of these patients, including the age of onset of end-stage renal disease (ESRD) and chronic renal failure (CRF; defined as creatinine clearance Յ 50 ml/min, calculated using the Cockroft and Gault formula), were analyzed. Of all the affected individuals clinically assessed, 117 (25.4%) had ESRD, 47 (10.2%) died without ESRD, 65 (14.0%) had CRF, and 232 (50.3%) had neither CRF nor ESRD at the last follow-up. Female patients, compared with male patients, had a later mean age of onset of ESRD (76.0 [95% CI, 73.8 Linear regression and renal survival analyses revealed that the location of PKD2 mutations did not influence the age of onset of ESRD. However, patients with splice site mutations appeared to have milder renal disease compared with patients with other mutation types (P Ͻ 0.04 by log rank test; adjusted for the gender effect). Considerable renal disease variability was also found among affected individuals with the same PKD2 mutations. This variability can confound the determination of allelic effects and supports the notion that additional genetic and/or environmental factors may modulate the renal disease severity in ADPKD.

The clinical use of conventional ultrasonography (US) in autosomal dominant polycystic kidney disease (ADPKD) is currently limited by reduced diagnostic sensitivity, especially in at-risk subjects younger than 30 years of age. In this single-center prospective study, we compared the diagnostic performance of MRI with that of high-resolution (HR) US in 126 subjects ages 16-40 years born with a 50% risk of ADPKD who underwent both these renal imaging studies and comprehensive PKD1 and PKD2 mutation screening. Concurrently, 45 healthy control subjects without a family history of ADPKD completed the same imaging protocol. We analyzed 110 at-risk subjects whose disease status was unequivocally defined by molecular testing and 45 unaffected healthy control subjects. Using a total of .10 cysts as a test criterion in subjects younger than 30 years of age, we found that MRI provided both a sensitivity and specificity of 100%. Comparison of our results from HR US with those from a previous study of conventional US using the test criterion of a total of three or more cysts found a higher diagnostic sensitivity (approximately 97% versus approximately 82%) with a slightly decreased specificity (approximately 98% versus 100%) in this study. Similar results were obtained in test subjects between the ages of 30 and 40 years old. These results suggest that MRI is highly sensitive and specific for diagnosis of ADPKD. HR US has the potential to rival the diagnostic performance of MRI but is both center-and operator-dependent.

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The absence of a positive family history (PFH) in 10%-25% of patients poses a diagnostic challenge for autosomal dominant polycystic kidney disease (ADPKD). In the Toronto Genetic Epidemiology Study of Polycystic Kidney Disease, 210 affected probands underwent renal function testing, abdominal imaging, and comprehensive and mutation screening. From this cohort, we reviewed all patients with and without an apparent family history, examined their parental medical records, and performed renal imaging in all available parents of unknown disease status. Subsequent reclassification of 209 analyzed patients revealed 72.2% (151 of 209) with a PFH, 15.3% (32 of 209) with disease, 10.5% (22 of 209) with an indeterminate family history, and 1.9% (four of 209) with PFH in retrospect. Among the patients with cases, we found two families with germline mosaicism and one family with somatic mosaicism. Additionally, analysis of renal imaging revealed that 16.3% (34 of 209) of patients displayed atypical PKD, most of which followed one of three patterns: asymmetric or focal PKD with PFH and an identified or mutation (15 of 34), asymmetric and PKD with proven or suspected somatic mosaicism (seven of 34), or focal PKD without any identifiable or mutation (eight of 34). In conclusion, PKD without an apparent family history may be due to disease, missing parental medical records, germline or somatic mosaicism, or mild disease from hypomorphic and mutations. Furthermore, mutations of a newly identified gene for ADPKD, , and somatic mosaicism need to be considered in the mutation-negative patients with focal disease.