Circulating succinate-modifying metabolites accurately classify and reflect the status of fumarate hydratase-deficient renal cell carcinoma.

Germline or somatic loss-of-function mutations of fumarate hydratase (FH) predispose patients to an aggressive form of renal cell carcinoma (RCC). Since other than tumor resection there is no effective therapy for metastatic FH-deficient RCC, an accurate method for early diagnosis is needed. Although MRI or CT scans are offered, they cannot differentiate FH-deficient tumors from other RCCs. Therefore, finding noninvasive plasma biomarkers suitable for rapid diagnosis, screening, and surveillance would improve clinical outcomes. Taking advantage of the robust metabolic rewiring that occurs in FH-deficient cells, we performed plasma metabolomics analysis and identified 2 tumor-derived metabolites, succinyl-adenosine and succinic-cysteine, as excellent plasma biomarkers for early diagnosis. These 2 molecules reliably reflected the FH mutation status and tumor mass. We further identified the enzymatic cooperativity by which these biomarkers are produced within the tumor microenvironment. Longitudinal monitoring of patients demonstrated that these circulating biomarkers can be used for reporting on treatment efficacy and identifying recurrent or metastatic tumors.

Curcumin alleviated oxidation stress injury by mediating osteopontin in nephrolithiasis rats

Purpose: To explore the role and mechanism of curcumin (Cur) in reducing oxidative stress damage in rats with nephrolithiasis induced by ethylene glycol (EG). Methods: Thirty male rats were divided into normal control, model, positive (10% potassium citrate), Cur-10 (10 mg/kg curcumin) and Cur-20 (20 mg/kg curcumin) groups. Results: The results of kidney tissue section stained by hematoxylin-eosin and von Kossa showed that curcumin treatment can inhibit the formation of kidney stones. The biochemical test results showed that the urea (Ur), creatinine (Cr), uric acid (UA), inorganic phosphorus and Ca2+ concentrations in urine decreased after being treated with curcumin. There were significant differences between different doses of curcumin (P < 0.05). Compared with the Cur-10 group, Cur-20 had a more significant inhibitory effect on malondialdehyde (MDA) (P < 0.05). In addition, reverse transcription polymerase chain reaction (PCR) detection and immunohistochemical results indicated that the osteopontin (OPN) in the kidney was significantly reduced after curcumin treatment. Conclusion: Curcumin could reduce the oxidative stress damage caused by EG-induced kidney stones.

Retrograde intrarenal surgery vs miniaturized percutaneous nephrolithotomy to treat lower pole renal stones 1.5-2.5 cm in diameter.

AIM: To compare the outcomes of retrograde intrarenal surgery (RIRS) and miniaturized percutaneous nephrolithotomy (mini-PCNL) in treating lower pole (LP) renal stones with a diameter of 1.5-2.5 cm. METHODS: A total of 216 patients who underwent mini-PCNL (n = 103) or RIRS n = 113) for LP stones with a diameter of 1.5-2.5 cm were enrolled between December 2015 and April 2017 at the Urology Department of Ningbo Urology and Nephrology Hospital. RESULTS: Significant differences were found in the hospital stay (9.39 ± 4.01 vs 14.08 ± 5.26, P < 0.0001) and hospitalization costs (2624.5 ± 513.36 vs 3255.2 ± 976.5, P < 0.0001) between the RIRS and mini-PCNL groups. The mean operation time was not significantly different between the RIRS group (56.48 ± 24.77) and the mini-PCNL group (60.04 ± 30.38, P = 0.345). The stone-free rates at the first postoperative day (RIRS vs mini-PCNL: 90.2% vs 93.2%, P = 0.822) and the second month postoperatively (RIRS vs mini-PCNL: 93.8% vs 95.1%, P = 0.986) were not significantly different. CONCLUSION: RIRS and mini-PCNL are both safe and effective methods for treating LP stones with a diameter of 1.5-2.5 cm. RIRS can be considered as an alternative to PCNL for the treatment for LP stones of 1.5-2.5 cm.

[The role RNA interference of alpha1, 3GT plays in resistance to complement mediated cytotoxicity of porcine endothelial cells].

OBJECTIVE: To evaluate whether RNA interference can protect porcine endothelial cells from complement mediated cytotoxicity. METHODS: Immortalized porcine aortic endothelial cells of the line PED were cultured and transfected with alpha1,3-galactosyltransferase (alpha1, 3-GT) specific siRNAs. Cells transfected with mismatch SiRNA was used as negative controls. Forty-eight hours later the cells were collected. The expression of alpha1, 3-GT mRNA was examined by RT-PCR. The expression of alpha-Gal was examined by flow cytometry. PED cells ere labeled with (51)Cr and mixed with normal human serum (NHS). The release of (51)Cr was measured by gamma-ray counter. Heat inactivated NHS (HINHS) was used as control. RESULTS: Two isoforms (isoform 1 and isoform 2) were amplified from the PED cells. The expression of alpha1, 3-GT in the PED cells transfected with SiRNA-1 was lower by 70% in comparison with the mock group (69% for the isoform 1 and 72% for the isoform 2, both P < 0.05). However, the expression of alpha1, 3-GT in the PED cells transfected with SiRNA21 was not different from those in the mock group and mismatch group (both P > 0.05). Flow cytometry showed that the average fluorescence intensity of the PED cells transfected with SiRNA-1 was 52, 9, significantly lower than that of the mismatch group and mock group (493.9 and 5-5.7 respectively, both P < 0.0). Fluorescence microscopy observed the "silence effect" of alphaGal after SiRNA-1 transfection. Added with 20% and 40% NHS, the cell dissolution rate of the SiRNA transfection group was lower than that of the mock group by 70% and 60% respectively. CONCLUSIONS: alpha1, 3GT gene silencing actually occurs following transfection of SiRNA-1. Porcine endothelial cells can be the targets of RNAi.