Chibing Huang

Platelet-Derived Growth Factor Receptor Beta: A Novel Urinary Biomarker for Recurrence of Non-Muscle-Invasive Bladder Cancer

Non-muscle-invasive bladder cancer (NMIBC) is one of the most common malignant tumors in the urological system with a high risk of recurrence, and effective non-invasive biomarkers for NMIBC relapse are still needed. The human urinary proteome can reflect the status of the microenvironment of the urinary system and is an ideal source for clinical diagnosis of urinary system diseases. Our previous work used proteomics to identify 1643 high-confidence urinary proteins in the urine from a healthy population. Here, we used bioinformatics to construct a cancer-associated protein-protein interaction (PPI) network comprising 16 high-abundance urinary proteins based on the urinary proteome database. As a result, platelet-derived growth factor receptor beta (PDGFRB) was selected for further validation as a candidate biomarker for NMIBC diagnosis and prognosis. Although the levels of urinary PDGFRB showed no significant difference between patients pre- and post-surgery (n = 185, P>0.05), over 3 years of follow-up, urinary PDGFRB was shown to be significantly higher in relapsed patients (n = 68) than in relapse-free patients (n = 117, P<0.001). The levels of urinary PDGFRB were significantly correlated with the risk of 3-year recurrence of NMIBC, and these levels improved the accuracy of a NMIBC recurrence risk prediction model that included age, tumor size, and tumor number (area under the curve, 0.862; 95% CI, 0.809 to 0.914) compared to PDGFR alone. Therefore, we surmise that urinary PDGFRB could serve as a non-invasive biomarker for predicting NMIBC recurrence.

A stable panel comprising 18 urinary proteins in the human healthy population

Just as biomarkers specific for diseases, biomarkers indicative of healthy conditions are valuable for the early diagnosis, monitoring, and prognosis of diseases. Our study focused on discovering via proteomics a stable panel of urinary proteins in the human healthy population. Urine samples were collected three times during 4 months from 100 male and 100 female healthy donors and analyzed through four different fractionation techniques (i.e. in‐gel, 2D‐LC, OFFGEL, and mRP) coupled with HPLC‐Chip‐MS/MS. Thus, 1641 urinary proteins were identified with a high confidence, among which 70 exhibiting an intergender/day variation <0.25 were selected and matched with the previously published five largest urinary proteomes to get 56 candidate proteins. Next, a panel comprising 18 intact urinary proteins was constructed by comparing the urinary proteomes via SDS‐PAGE and 2DE. Finally, such 18 urinary proteins were validated via enzyme‐linked immunosorbent assay in eight healthy individuals. Most of these proteins had been related to multiple rather than to single diseases. Therefore, we surmise that this protein set could be used as a biomarker to assess the human health status. Further determinations of the normal fluctuations of the single urinary proteins in this series using samples from large numbers of healthy individuals are required prior to any application in clinical settings.

Preclinical evaluation of a newly designed ureteral stent and magnetic retrieval catheter for minimally invasive stent removal.

OBJECTIVE To develop a simple minimally invasive method for ureteral stent removal that does not require cystoscopy or fluoroscopic guidance. MATERIALS AND METHODS We developed a novel ureteral stent comprising the main body of a stent and an iron oxide-coated net that was woven of processed polyester sutures. The ureteral stent was retrieved by a magnetic retrieval catheter with small hooks on the neck surface. Detailed analysis of the necessary mechanical and magnetic properties was performed, and we conducted retrieval tests of the ureteral stent from a specially designed urinary system model. RESULTS The breaking strength and Young modulus of the processed polyester sutures were 10.12 ± 0.30 N and 9143 ± 7 N/tex, respectively. Thermogravimetric tests showed that the iron (III) oxide powders on the processed sutures accounted for 23% of the total weight. The magnetization value of the magnetic retrieval catheter was 578 emu/g. The dissolution times of polyvinyl alcohol wrapped the net in saline or urine were 24.2 ± 2.0 and 23.6 ± 3.1 hours, respectively. All stents in both the experimental and the control groups were successfully removed from the specially designed urinary model. However, the retrieval time in the experimental group was significantly shorter than that in the control group (38.6 ± 12.6 vs 59 ± 15.7 seconds; P <.05). CONCLUSION Ureteral stent removal using a magnetic retrieval catheter with small capture devices is considered feasible. This technique is easy to learn and should be considered as suitable for use on an outpatient basis.

Weakened IL-15 Production and Impaired mTOR Activation Alter Dendritic Epidermal T Cell Homeostasis in Diabetic Mice

Diabetes is associated with impaired wound healing, which may be caused primarily by a deficiency in dendritic epidermal T cells (DETCs). In the epidermis, IL-15, IGF-1, and mTOR are known to regulate the maintenance of DETCs; however, it is unclear how these molecules may intersect to regulate DETC homeostasis in diabetes. Here, we show that the reduction of DETCs in the epidermis of diabetic mice is caused by altered homeostasis mediated by a reduction in IL-15 levels. Both impaired mTOR activation and reduction of IL-15 in the epidermis play important roles in DETC homeostasis. Moreover, IGF-1 drives keratinocytes to produce IL-15. The activation of IL-15 is dependent on mTOR, and conversely, mTOR regulates IGF-1 production in DETC, in a classic feedback regulatory loop. Our data suggest that in the setting of diabetes, reduced IGF-1, impaired mTOR pathway activation and reduced IL-15 in the epidermis function coordinately to promote altered DETC homeostasis and delayed skin wound closure.