LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer.

Epigenetic alteration is a key feature that contributes to the progression of bladder cancer (BC) and long non-coding RNAs serve crucial role in the epigenetic modulation. This study was designed to explore the epigenetic regulation of LINC00592 in BC. LINC00592 expression in BC was examined. Then, LINC00592 was silenced in BC cell followed by cell behavior analyses using CCK-8, transwell, western blot, or flow cytometry. Potential downstream target of LINC00592 was explored using RNA pull-down assay and methylation of WIF1 was determined using methylated-specific PCR. In addition, WIF1 or/and LINC00592 were silenced in BC cells followed by cell behavior analyses to explore the regulation between them. Upregulation of LINC00592 was significantly detected in BC tissues and cells. In BC cells silencing LINC00592 suppressed the proliferation, migration, and epithelial-mesenchymal transitions (EMT), but enhanced apoptosis. Moreover, LINC00592 recruited DNMT1, DNMT3A, and DNMT3B to enhance WIF1 promoter methylation. In addition, WIF1 overexpression suppressed the proliferation, migration, as well as EMT, but enhanced apoptosis. Silencing WIF1 significantly attenuated the role of silencing LINC00592 in suppressing the proliferative, migratory, and EMT ability of BC cells, and increasing the apoptosis. LINC00592 promoted the growth and metastasis of BC via enhancing the promoter methylation of WIF1 and decreasing WIF1 transcription.

Oxygen Vacancy Engineering of Fe-Doped NiMoO4 for Electrocatalytic N2 Fixation to NH3.

Electrochemical nitrogen reduction reaction (NRR) is a promising method for ammonia synthesis under ambient conditions. However, the NRR performance is limited to an extremely strong N≡N bond in N2 and the competing hydrogen evolution reaction. Introducing oxygen vacancies (OVs) has been considered as a forceful means to accelerate the sluggish NRR reaction kinetics. Herein, we reported the design of Fe-doped NiMoO4 catalysts for NRR. Fe doping can increase the amount of OVs in the catalyst and contribute to lattice strain enhancement, thereby leading to the improvement of the electron transport rate and catalytic active for NRR. In 0.1 M Na2SO4 solution, the 5% Fe-NiMoO4 catalyst achieves a NH3 yield rate of 15.36 µg h-1 mgcat.-1 and a Faradaic efficiency of 26.85% under -0.5 V versus RHE. Furthermore, the 5% Fe-NiMoO4 catalyst exhibits excellent stability (up to 13 h) during the reaction.

Stalk-derived carbon dots as nanosensors for Fe3+ ions detection and biological cell imaging.

Introduction: Iron is one of the most important needed elements for the growth and reproduction of living organisms. The detection of iron levels is important and developing fluorescent probes with excellent sensitivity for Fe3+ ions is of great significance. Carbon dot (CDs) is a new type of fluorescent nanomaterial based on abundant and low-cost carbon elements. The use of widely distributed renewable agricultural waste straw as a carbon precursor to prepare CDs sensor can not only reduce the pollution caused by burning straw to the atmospheric environment, but also achieve the transformation of resources from waste to treasure. Methods: In this study, CDs were obtained from corn stalk powder by pyrolysis and microwave process. The sensitivity and linear response range of CDs sensor was studied through analyzing the effect of different Fe3+ ions concentrations on the fluorescence quenching. The application of CDs in biological cell imaging was investigated using HGC-27 cells. Results: The fluorescence quenching showed a good linear relationship with the Fe3+ concentration in the range from 0 to 128 µM, and a low detection limit of 63 nM. In addition, the CDs have high recognition for Fe3+ ions. Meanwhile, the CDs have a low cytotoxicity and desirable biocompatibility, allowing the multicolor living cell imaging. Conclusion: The prepared CDs can be used as fluorescent sensors for the selective detection of Fe3+ ions and biological cell imaging. Our results supported that the conversion of agricultural waste into carbon nanomaterials has great potential to be developed.

Curcumin attenuates renal interstitial fibrosis of obstructive nephropathy by suppressing epithelial-mesenchymal transition through inhibition of the TLR4/NF-кB and PI3K/AKT signalling pathways.

CONTEXT: Renal interstitial fibrosis (RIF) is characterized by the accumulation of inflammatory cytokines and epithelial-mesenchymal transition (EMT). Curcumin exerts antifibrogenic, anti-inflammatory and antiproliferative effects. OBJECTIVE: To explore the mechanisms underlying the effects of curcumin on RIF. MATERIALS AND METHODS: Eight-week-old male C57BL/6 mice were intragastrically administered curcumin (50 mg/kg/day) for 14 days after undergoing unilateral ureteral obstruction (UUO) operations. Renal function (blood urea nitrogen [BUN] and serum creatinine [Scr]) and inflammatory cytokine levels were tested using colorimetric assays and ELISA, respectively. EMT markers were evaluated through immunohistochemistry, western blotting and qPCR. Transforming growth factor beta 1 (TGF-ß1; 10 ng/mL) and lipopolysaccharides (LPS; 100 ng/mL) were used to stimulate EMT and an inflammatory response in human renal proximal tubular epithelial (HK-2) cells, respectively, for further investigation. RESULTS: In vivo, curcumin significantly improved the levels of BUN and Scr by 28.7% and 21.3%, respectively. Moreover, curcumin reduced the levels of IL-6, IL-1ß and TNF-α by 22.5%, 30.3% and 26.7%, respectively, and suppressed vimentin expression in UUO mice. In vitro, curcumin reduced the expression of vimentin and α-smooth muscle actin in TGF-ß1-induced HK-2 cells. In LPS-induced HK-2 cells, curcumin decreased the release of IL-6, IL-1ß and TNF-α by 43.4%, 38.1% and 28.3%, respectively. In addition, curcumin reduced the expression of TLR4, p-PI3K, p-AKT, p-NF- κB and p-IκBα in both LPS- and TGF-ß1-induced HK-2 cells. DISCUSSION AND CONCLUSIONS: Curcumin repressed EMT and the inflammatory response by inhibiting the TLR4/NF-κB and PI3K/AKT pathways, demonstrating its potential utility in RIF treatment.

m6A-induced lncRNA MALAT1 aggravates renal fibrogenesis in obstructive nephropathy through the miR-145/FAK pathway.

Renal fibrosis is a key factor in chronic kidney disease (CKD). Long non-coding RNAs (lncRNAs) play important roles in the physiological and pathological progression of human diseases. However, the roles and underlying mechanisms of lncRNAs in renal fibrosis still need to be discovered. In this study, we first displayed the increased lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) expression in renal fibrosis in patients with obstructive nephropathy (ON). Then we found that transforming growth factor beta 1 (TGF-ß1) induced epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) protein deposition, which promoted the viability, proliferation and migration of human renal proximal tubular epithelial (HK2) cells. Next, MALAT1/miR-145/focal adhesion kinase (FAK) pathway was confirmed to play an importment role in TGF-ß1-induced renal fibrosis. In addition, the MALAT1/miR-145/FAK pathway was involved in the effect of dihydroartemisinin (DHA) on TGF-ß1-induced renal fibrosis in vitro and in vivo. Furthermore, m6A methyltransferase methyltransferase-like 3 (METTL3) was shown to be the main methyltransferase of m6A modification on MALAT1.

[Efficacy of laparoscopic urinary tract reconstruction with intraoperative retrograde ureteroscopy-assisted technique for treatment of complex ureteral stricture].

OBJECTIVE: To investigate the feasibility and clinical effects of the laparoscopic urinary tract reconstruction with intraoperative retrograde ureteroscopy-assisted technique for the treatment of complex ureteral stricture. 
 Methods: The clinical data of 16 patients with complicated ureteral stricture treated by the laparoscopic urinary tract reconstruction with intraoperative retrograde ureteroscopy-assisted technique from February 2016 to June 2018 were retrospectively analyzed. All 16 patients were iatrogenic stenosis. There were 4 cases of severe hydronephrosis in the affected side, 7 cases of moderate hydronephrosis, and 5 cases of mild hydronephrosis. According to the specific location and length of the ureteral stricture, the corresponding surgical method was selected. 
 Results: All patients successfully completed the operation without conversion to open surgery and organ injury. After the operation, the patients were followed up for 8-18 months. The hydronephrosis of all patients was relieved to varying degrees, and no ureteral restenosis occurred. 
 Conclusion: The laparoscopic urinary tract reconstruction with intraoperative retrograde ureteroscopy-assisted technique can accurately locate the stenosis segment, test the anastomosis effect, expand the inflammatory stenosis, and improve the end-to-end anastomosis of the distal ureteral stricture, which is a new and effective technique for the treatment of complex ureteral strictures.

PTEN improve renal fibrosis in vitro and in vivo through inhibiting FAK/AKT signaling pathway.

Renal fibrosis, the ultimate common pathway of progressive nephropathy, is characterized by excess accumulation and deposition of extracellular matrix (ECM) within the renal interstitium and glomeruli, finally resulting in end-stage kidney failure. TGFß1 is not only abnormally increased during fibrosis but also involved in ECM induction and accumulation. Based on the bioinformative analyses, phosphatase and tensin homolog deleted on chromosome ten (PTEN) and focal adhesion kinase (FAK) signaling pathway might be involved in TGFß1 functions on renal fibrosis development. In the present study, fibrosis was induced in HK-2 cells using TGFß1 and PTEN expression was significantly suppressed by 24 or 48 hours TGFß1 treatment. PTEN overexpression in HK-2 cells improved TGFß1-induced fibrosis within α-SMA and E-cadherin. According to the KEGG signaling pathway annotation analyses on microarray profiles (GSE23338 and GSE20247) and immunoblotting validation, FAK signaling might be involved in PTEN functions in TGFß1-induced fibrosis. PTEN overexpression significantly inhibited TGFß1- or unilateral ureteral obstruction (UUO)-induced FAK signaling pathway activation both in vitro and in vivo; more importantly, PTEN silence enhanced TGFß1- or UUO-induced fibrosis, while FAK inhibitor PF567721 significantly reversed the effects of PTEN silence, indicating that PTEN exerted its effects on TGFß1- and UUO-induced fibrotic development in vitro and in vivo via inhibiting FAK signaling pathway. In summary, these findings indicate that PTEN could improve cellular fibrotic changes and renal fibrosis via inhibiting FAK/AKT signaling pathway. Restoring PTEN expression to target FAK/AKT signaling pathway might be a potent strategy for renal fibrosis treatment.

Dihydroartemisinin attenuates renal fibrosis through regulation of fibroblast proliferation and differentiation.

AIMS: Renal fibrosis is the most common final stage of progressive renal disease, characterized by fibroblast proliferation, fibroblast-to-myofibroblast differentiation and excessive accumulation of extracellular matrix. Dihydroartemisinin (DHA) exerts antitumor, antibacterial, and antifibrotic effects. The aim of this study was to determine whether DHA has beneficial effects on unilateral ureteral obstruction (UUO)-induced renal fibrosis in mice and to examine explore the underlying possible mechanisms. MATERIALS AND METHODS: Eight-week-old male C57BL/6 mice were intragastrically administered DHA for 14 consecutive days after UUO operation. Afterward, interstitial collagen deposition, expression of collagen I and III, fibronectin, α-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), and S100 calcium-binding protein A4 (S100A4) were assessed in the kidneys. Transforming growth factor beta 1 (TGF-ß1)-induced primary human kidney fibroblasts were treated with DHA to further investigate the mechanism underlying its action. KEY FINDINGS: In vivo, DHA reduced UUO-induced morphological and pathological changes and the degree of renal fibrosis. In addition, DHA mitigated fibroblast proliferation and differentiation in kidney tissue induced by UUO. In vitro, DHA significantly attenuated the TGF-ß1-induced primary human kidney fibroblast proliferation and fibroblast-to-myofibroblast differentiation. Moreover, treatment with DHA attenuated the up-regulation of phosphorylation of phosphatidylinositol-3-kinase (PI3K) and protein kinase B (AKT) in UUO model and TGF-ß1-induced primary human kidney fibroblasts. SIGNIFICANCE: We provide in vivo and in vitro evidence that DHA may relieve renal fibrosis through regulation of fibroblast proliferation and differentiation by mitigating the PI3K/AKT pathway. DHA may potentially be used as a therapeutic antifibrotic agent for the treatment of renal fibrosis.

Application of Three-Dimensional Visualization Technology in Laparoscopic Surgery for Pheochromocytoma/Paraganglioma: A Single-Center Experience.

OBJECTIVE: To compare the feasibility of three-dimensional visualization technology (3DVT) with that of routine computed tomography (CT) examination during planning of laparoscopic surgery for pheochromocytoma (PHEO) and paraganglioma (PGL) and the effects on operative and postoperative outcomes. PATIENTS AND METHODS: The clinical data for 36 patients who underwent laparoscopic surgery for PHEO/PGL in our department from January 2016 to April 2017 were analyzed retrospectively. Fourteen patients underwent laparoscopic surgery for PHEO/PGL after preoperative 3DVT-based assessment and 22 after conventional CT examination. The demographic parameters, surgical procedures used, and perioperative outcomes were compared between the two groups. Data were entered into a Microsoft Excel worksheet and analyzed using SPSS version 24.0. RESULTS: No significant differences were found between the groups with regard to age, gender, body mass index, tumor size, surgical approach, estimated blood loss, mean length of hospital stay, number of hypertensive and hypotensive episodes during surgery, peak blood pressure (BP) values during tumor handling, and minimum values after tumor excision. However, the operating time was significantly shorter and the fluctuations in BP were significantly lower in the 3DVT group. CONCLUSIONS: 3DVT is a feasible and useful preoperative assessment method in patients undergoing laparoscopic surgery for PHEO/PGL. This imaging technique accurately shows the relationship between the tumor and peripheral structures and aids the surgeon's understanding of the anatomic structure in the operative area and in surgical planning.

Anaerobic benzene biodegradation by a pure bacterial culture of Bacillus cereus under nitrate reducing conditions.

A pure culture using benzene as sole carbon and energy sources was isolated by screening procedure from gasoline contaminated soil. The analysis of the 16S rDNA gene sequence, morpholpgical and physiological characteristics showed that the isolated strain was a member of genus Bacillus cereus. The biodegradation performance of benzene by B. cereus was evaluated, and the results showed that benzene could be efficiently biodegraded when the initial benzene concentration was below 150 mg/L. The metabolites of anaerobic nitrate-dependent benzene oxidation by strain B. cereus were identified as phenol and benzoate. The results of substrate interaction between binary combinations for benzene, phenol and benzoate showed that the simultaneous presence of benzene stimulated the degradation of benzoate, whereas the addition of benzene inhibited the degradation of phenol. Benzene degradation by B. cereus was enhanced by the addition of phenol and benzoate, the enhanced effects were more pronounced at higher concentration. To our knowledge, this is the first report that the isolated bacterial culture of B. cereus can efficiently degraded benzene under nitrate reducing conditions.