(111) Facet-oriented Cu2Mg Intermetallic Compound with Cu3-Mg Sites for CO2 Electroreduction to Ethanol with Industrial Current Density.

The efficient ethanol electrosynthesis from CO2 is challenging with low selectivity at high CO2 electrolysis rates, due to the competition with H2 and other reduction products. Copper-based bimetallic electrocatalysts are potential candidates for the CO2-to-ethanol conversion, but the secondary metal has mainly been focused on active components (such as Ag, Sn) for CO2 electroreduction, which also promote selectivity of ethylene or other reduction products rather than ethanol. Limited attention has been given to alkali-earth metals due to their inherently active chemical property. Herein, we rationally synthesized a (111) facet-oriented nano Cu2Mg (designated as Cu2Mg(111)) intermetallic compound with high-density ordered Cu3-Mg sites. The in situ Raman spectroscopy and density function theory calculations revealed that the Cu3 - δ $_{^{\rm{{\rm \delta} }} }$ --Mg- δ $_{^{\rm{{\rm \delta} }} }$ + active sites allowed to increase *CO surface coverage, decrease reaction energy for *CO-CO coupling, and stabilize *CHCHOH intermediates, thus promoting the ethanol formation pathway. The Cu2Mg(111) catalyst exhibited a high FEC2H5OH of 76.2±4.8 % at 600 mA⋅cm-2, and a peak value of |jC2H5OH| of 720±34 mA⋅cm-2, almost 4 times of that using conventional Cu2Mg with (311) facets, comparable to the best reported values for the CO2-to-ethanol electroreduction.

Tube Formation Capability and Chemotaxis of Skin Pericytes.

BACKGROUND: Pericytes (PCs), the critical components of vessels, are implicated in wound repair. This study aimed to explore the roles of PCs in wound healing and angiogenesis. METHODS: Skin PCs and human dermal microvascular endothelial cells (HDMECs) were isolated from patients' upper eyelid skin. Immunofluorescence staining was used to characterize the morphology of PCs. Tube formation and transwell chemotaxis assays were performed to explore PC's tube-forming capability and chemotaxis. Finally, we investigated the effects of PCs and endothelial cells on wound repair using skin wound of a rat model. RESULTS: Skin PCs exhibited a double-protrusion structure and characteristic antigen expression of neural/glial antigen 2 (NG2)+/platelet-derived growth factor receptor-ß (PDGFR-ß)+/alpha-smooth muscle actin (α-SMA)+/CD31-. Skin PCs could directly form lumen-like structures in a two dimensional (2D) culture environment, and mild hypoxia and starvation promoted the lumen-like structure formation. Furthermore, skin PCs quickly formed more stable lumen-like structures than HDMECs in matrigel, and they recruited HDMECs in a three dimensional (3D) culture environment. Transwell chemotaxis assay showed that PCs and HDMECs were chemotactic to each other. PCs could develop lumen-like structures in the skin wounds of rat models. The number of PCs mounted in wounded skin was compared to normal skin. The ratio of PCs to endothelial cells gradually increased after skin injury and reached its maximum on the 3rd day. CONCLUSIONS: Skin PCs have an excellent tube-forming capability and chemotaxis to endothelial cells. PCs might promote wound repair by recruiting endothelial cells.

High-power quantum-limited 35 MHz photodiode and classical laser noise suppression.

To benefit high-power interferometry and the creation of low-noise light sources, we develop a simple lead-compensated photodetector enabling quantum-limited readout from 0.3 to 10 mW and 10 kΩ gain from 85 Hz to 35 MHz, with a noise equivalent power of 9 pW/Hz. Feeding the detector output back to an intensity modulator, we suppress the classical amplitude noise of a commercial 1550 nm fiber laser to the shot noise limit over a bandwidth of 700 Hz-200 kHz, observing no degradation to its (nominally ∼100 Hz) linewidth.

Botulinum toxin type A activates protective autophagy by modulating endoplasmic reticulum stress in hypoxia/reoxygenation-treated endothelial cells.

Botulinum toxin type A (BTXA) previously protected endothelial cells in free skin flaps from ischemia/reperfusion injury by inducing autophagy. Endoplasmic reticulum (ER) stress-autophagy activation may have a role in BTXA-antagonized ischemia/reperfusion damage in human dermal microvascular endothelial cells (HDMECs), however, this has yet to be proven. HDMECs were pretreated with BTXA at various concentrations for 12 h before being subjected to hypoxia and reoxygenation (H/R). Cell Count Kit 8 (CCK8) and Western blot (WB) data showed that H/R treatment significantly increased the expression of ER stress (GRP78, CHOP) and autophagy (LC3II/I, Beclin-1) proteins. The optimal BTXA pretreatment concentration was 1.6 U/mL, which resulted in the highest levels of cell survival and expression of ER stress and autophagy. Following pretreatment with 1.6 U/mL BTXA and the addition of the ER stress inducer Thapsigargin (Tg), the ER stress inhibitor 4-phenylbutyrate (4-PBA), and the inhibitor of autophagy Bafilomycin A1 (Baf A1), respectively, HDMECs were then subjected to H/R treatment. Cell survival and the percentage of ethynyldeoxyuridine-labeled cells in the BTXA pretreatment groups were reduced by the addition of Tg, 4-PBA, and Baf A1. While the expression of GRP78, CHOP, and LC3 was upregulated by Tg and Baf A1, it was downregulated by 4-PBA. The findings showed that ER stress produced by BTXA pretreatment triggers protective autophagy and protects HDMECs from H/R damage. There were no cytoprotective effects from either excessive activation or reduction of ER stress. Our results are consistent with the notion that autophagy and moderate ER stress are critical for cellular longevity and, consequently, functional integrity and may represent a potential therapeutic target.

A method to isolate human dermal microvascular pericytes without the use of magnetic beads sorting in vitro.

Human dermal microvascular pericytes (HDMPCs) are a critical component of the skin flap microvasculature and play a role in regulating flap blood flow and integrity. Pericytes were isolated mostly via magnetic bead sorting in the published literature. In this study, we discuss in detail how to separate and concentrate pericytes from human facial flaps using enzyme digestion and differential adherence instead of magnetic bead sorting. Cultured HDMPCs were seen to have well-spread irregular edges, with most cells having two longitudinal pericytic processes. The phalloidin staining revealed that HDMPCs had prominent stress fibers, and the nucleus deviated to the side that interacted with the neighboring pericytic processes. Flow cytometry analysis showed that the positive rates of NG2 in the first and second passages were 91.2% ± 0.7% and 98.2% ± 0.1% separately. And the immunofluorescence and western blot results demonstrated a positive expression of α smooth muscle actin (αSMA), platelet-derived growth factor receptor ß (PDGFRß), and NG-2, while the endothelial cell marker CD31 was negatively expressed. In summary, we established a straightforward methodology for selectively isolating and identifying HDMPCs as well as generating high-purity cell cultures in vitro without the use of magnetic bead sorting.

[Corrigendum] Curcumin reverses benzidine-induced epithelial-mesenchymal transition via suppression of ERK5/AP-1 in SV-40 immortalized human urothelial cells.

Following the publication of the above article, an interested reader drew to the authors' attention that, for the Transwell invasion assays shown in Fig. 5D on p. 1326, the images selected for the '0 µM benzidine / 0 µM curcumin' and '0 µM benzidine / 1 µM curcumin' experiments were overlapping, such that these data appeared to have been derived from the same original source. After having consulted their original data, the authors have realized that the '0 µM benzidine / 1 µM curcumin' data panel was selected incorrectly. The revised version of Fig. 5, showing the correct data for the '0 µM benzidine / 1 µM curcumin' data panel in Fig. 5D, is shown on the next page. The authors regret that this error went unnoticed prior to the publication of this article, and thank the Editor of International Journal of Oncology for allowing them the opportunity to publish this corrigendum. All the authors agree with the publication of this corrigendum; furthermore, they also apologize to the readership of the journal for any inconvenience caused.[International Journal of Oncology 50: 1321­1329, 2017; DOI: 10.3892/ijo.2017.3887].

Long non-coding RNA SNHG1 promotes bladder cancer progression by upregulating EZH2 and repressing KLF2 transcription.

OBJECTIVE: Long Non-Coding RNAs (LncRNAs) act as an indispensable role in cancer development. The study aimed to investigate the role and mechanism of lncRNA Small Nucleolar RNA Host Gene 1 (SNHG1) in Bladder Cancer (BC) progression. METHOD: The expression, prognostic value, diagnostic value, and correlation of SNHG1, Enhancer of Zeste 2 polycomb repressive complex 2 subunit (EZH2), and Kruppel Like Factor 2 (KLF2) were analyzed through bioinformatics analysis. The expression was also validated in BC tissues and cell lines. Besides, their regulation and binding were tested via qPCR, Western blot, Dual-Luciferase Reporter Assay (DLRA), Argonaute RISC catalytic component 2-RNA Immunoprecipitation (AGO2-RIP), and Chromatin Immunoprecipitation (ChIP). A xenograft model in nude mice was also established. RESULTS: SNHG1 was significantly overexpressed in BC tissues and cells. Importantly, SNHG1 was associated with poor survival, and ROC curves revealed high diagnostic values. Moreover, by CCK8, wound healing, transwell, and Western blot analysis, SNHG1 knockdown significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of BC cells. Additionally, in vivo experiments showed that silencing SNHG1 hindered tumorigenesis and tumor growth. Regarding mechanism, the results of AGO2-RIP, ChIP or DLRA showed that SNHG1 played different roles at diverse subcellular sites. In the cytoplasm, SNHG1 acted as a competing endogenous RNA for miR-137-3p to promote EZH2 expression. In the nucleus, SNHG1 could interact with EZH2 to inhibit KLF2 transcription. CONCLUSION: Our study elucidated that SNHG1 formed a regulatory network and played an oncogenic role in BC, which provided a novel therapeutic target for BC treatment.

Enhancement of nitrogen removal by a modular design of vertical flow constructed wetlands with a plant carbon source: Optimization of carbon dosage for nitrogen removal, practicability evaluation and strategy exploration for water quality control.

The requirement of artificial aeration for increasing nitrogen removal in vertical flow constructed wetlands (VFCWs) brings extra energy consumption and complex maintenance. The feasibility of a modular design to replace artificial aeration for partially saturated VFCWs with palm bark as a carbon source (PSVFCW-pb) to achieve water quality control, especially nitrogen removal was evaluated. The PSVFCW-pb with a spatially separate structure and perforated peripheries for better oxygen diffusion had a promising total nitrogen removal (e.g., 66.4% at a dosage of 1.435 g/L of palm bark pretreated at 120 °C for 40 min) without additional aeration, while organic carbon removal was nearly unaffected. An appropriate increase of the palm bark dosage (≤1.435 g/L) resulted in higher nitrogen removal; however, a more palm bark (1.875 g/L) could not further increase nitrogen removal but caused color pollution. In addition, the removal of nitrogen by the modularized PSVFCW-pb was more sensitive to the ambient temperature than the removal of organic carbon and phosphorus, and the higher temperature was preferable. Notably, the more attractive property of the modular design is its great potential to improve nitrogen removal by conveniently altering the number and/or scale of oxic and oxygen-free modules. Finally, the relationships between the hydraulic load and inflow concentration were explored, by which the suitable hydraulic load could be flexibly adjusted based on real-time water quality to meet the specified surface water quality criteria in different seasons. This study provides a reliable CW design for controlling nutrient pollution in surface waters.

Preparation and evaluation of a chitosan modified biochar as an efficient adsorbent for pipette tip-solid phase extraction of triazine herbicides from rice.

The low allowable limit of triazine herbicides (THs) in rice makes it imperative to develop novel sample pretreatment methods for extraction and preconcentration of THs. Herein, a phosphoric acid activated biochar (PBC) was prepared and modified by chitosan (CS). For THs with different polarities, CS-PBC with multiple interaction sites exhibited satisfactory chemisorption. On this basis, a CS-PBC-based pipette tip-solid phase extraction (PT-SPE) was developed combined with HPLC to extract THs from rice. Low limits of detection (1.41-3.35 ng g-1), satisfactory linearity (0.01-2.00 µg g-1, R2 > 0.9974) and recoveries (96.13-116.25 %) were obtained with acceptable inter-day and intra-day precision (RSD ≤ 13.60 %). CS-PBC showed superior performance to three commercial single-mode adsorbents and comparable results to a hydrophilic-lipophilic balance adsorbent. The study explored the feasibility of PT-SPE for extracting THs from rice and broadened the application of plant biochar as an environmentally-friendly matrix in food sample pretreatment.

Promising energy transfer system between fuorine and nitrogen Co-doped graphene quantum dots and Rhodamine B for ratiometric and visual detection of doxycycline in food.

A novel sensor based on dual emissive fluorescent graphene quantum dots is developed for a rapid, selective, sensitive and visual detection of doxycycline (DOX). The ratiometric fluorescent probe is designed by grafting fluorescent group (Rhodamine B, RhB) on F, N-doped graphene quantum dots (FNGQDs). In the presence of DOX, the fluorescence at 466 nm is remarkably quenched due to inner filter effect and fluorescence resonance energy transfer, whereas the peak at 592 nm is attenuated slightly due to the energy transfer in the emission peaks of FNGQDs and RhB functional group. The sensor shows good linear relationship from 0.04 to 100 µM with a low detection limit of 40 nM. Furthermore, the flexible solid-state fluorescent sensing platform is used for detecting DOX in milk, pork and water samples. Therefore, this dual-emission FGQD-RhB can be used as a high-performance fluorescent and visual sensor for food safety and environmental monitoring.

Cholecalciferol pretreatment ameliorates ischemia/reperfusion-induced acute kidney injury through inhibiting ROS production, NF-κB pathway and pyroptosis.

Acute kidney injury (AKI) is a common complication in patients with potentially life-threatening diseases, and it is also usually associated with unacceptable morbidity and mortality rates. Therefore, new and efficient therapies are urgently required to relieve AKI. It is well known that, reactive oxygen species (ROS), the NF-κB signaling pathways and pyroptosis are involved in AKI induced by ischemia/reperfusion (I/R). The present study seeks to further confirm the internal relationship between vitamin D deficiency and I/R-induced AKI in patients, and to explore the underlying mechanisms of ROS, NF-κB signaling pathways and pyroptosis in the renal ischemia-reperfusion injury, as well as investigating the protective role of cholecalciferol. Patients with vitamin D deficiency show worse renal function reflected by postoperative glomerular filtration rate (GFR) and more release of proinflammatory cytokine IL-1ß and IL-18. Renal cell injury and renal dysfunction induced by I/R surgery were attenuated in the ICR mice administered with cholecalciferol. Cholecalciferol reduced ROS production, suppressed activated NF-κB signaling, and inhibited gasdermin D (GSDMD, a pyroptosis execution protein)-mediated pyroptosis. Cholecalciferol therefore has potential, as a clinical drug, to protect renal function in I/R-induced AKI through reducing ROS production, NF-κB activation and GSDMD-mediated pyroptosis.

Long non-coding RNA SNHG1 promotes bladder cancer progression by upregulating EZH2 and repressing KLF2 transcription

Abstract Objective: Long Non-Coding RNAs (LncRNAs) act as an indispensable role in cancer development. The study aimed to investigate the role and mechanism of lncRNA Small Nucleolar RNA Host Gene 1 (SNHG1) in Bladder Cancer (BC) progression. Method: The expression, prognostic value, diagnostic value, and correlation of SNHG1, Enhancer of Zeste 2 polycomb repressive complex 2 subunit (EZH2), and Kruppel Like Factor 2 (KLF2) were analyzed through bioinformatics analysis. The expression was also validated in BC tissues and cell lines. Besides, their regulation and binding were tested via qPCR, Western blot, Dual-Luciferase Reporter Assay (DLRA), Argonaute RISC catalytic component 2-RNA Immunoprecipitation (AGO2-RIP), and Chromatin Immunoprecipitation (ChIP). A xenograft model in nude mice was also established. Results: SNHG1 was significantly overexpressed in BC tissues and cells. Importantly, SNHG1 was associated with poor survival, and ROC curves revealed high diagnostic values. Moreover, by CCK8, wound healing, transwell, and Western blot analysis, SNHG1 knockdown significantly inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of BC cells. Additionally, in vivo experiments showed that silencing SNHG1 hindered tumorigenesis and tumor growth. Regarding mechanism, the results of AGO2-RIP, ChIP or DLRA showed that SNHG1 played different roles at diverse subcellular sites. In the cytoplasm, SNHG1 acted as a competing endogenous RNA for miR-137-3p to promote EZH2 expression. In the nucleus, SNHG1 could interact with EZH2 to inhibit KLF2 transcription. Conclusion: Our study elucidated that SNHG1 formed a regulatory network and played an oncogenic role in BC, which provided a novel therapeutic target for BC treatment.

Modified vein clamping technique for renal cell carcinoma complicated with level I-II IVC thrombi: a study at a single centre.

OBJECTIVES: To share our initial experience with the modified vein clamping technique for the treatment of renal cell carcinoma complicated with level I-II IVC thrombi. METHODS: From March 2018 to April 2021, 11 patients with renal cell carcinoma (RCC) involving an IVC tumour thrombus were admitted to our hospital. They all underwent laparoscopic radical nephrectomy and IVC thrombectomy (LRN-IVCTE) using a modified vein clamping technique. RESULTS: All procedures were successfully completed without conversion to open surgery. The median operative time was 185.00 min (145.00-216.00 min); the median estimated blood loss was 200.00 ml (155.00-300.00 ml), and four patients received an intraoperative transfusion. In addition, the median IVC clamping time was 18.00 min (12.00-20.00 min); the median postoperative hospital stay was 6.00 days (4.00-7.00 days), while the median follow-up period was 28.00 months (4.00-34.00 months). CONCLUSIONS: The modified vein clamping technique for the treatment of renal cell carcinoma complicated with level I-II IVC thrombi may be a safe and technically feasible alternative technique.

Monitored wet-etch removal of individual dielectric layers from high-finesse Bragg mirrors.

It is prohibitively expensive to deposit customized dielectric coatings on individual optics. One solution is to batch-coat many optics with extra dielectric layers, then remove layers from individual optics as needed. Here we present a low-cost, single-step, monitored wet etch technique for reliably removing individual SiO2 and Ta2O5 dielectric layers, in this case from a high-reflectivity fiber mirror. By immersing in acid and monitoring off-band reflected light, we show it is straightforward to iteratively (or continuously) remove six bilayers. At each stage, we characterize the coating performance with a Fabry-Pérot cavity, observing the expected stepwise decrease in finesse from 92,000 ± 3,000 to 3, 950 ± 50, finding no evidence of added optical losses. The etch also removes the fiber's sidewall coating after a single bilayer, and, after six bilayers, confines the remaining coating to a 60-µm-diameter pedestal at the center of the fiber tip. Vapor etching above the solution produces a tapered "pool cue" cladding profile, reducing the fiber diameter (nominally 125 µm) to 95 µm at an angle of ∼0.3° near the tip. Finally, we note that the data generated by this technique provides a sensitive estimate of the layers' optical depths. This technique could be readily adapted to free-space optics and other coatings.

Retroperitoneal vs transperitoneal laparoscopic lithotripsy of 20-40 mm renal stones within horseshoe kidneys.

BACKGROUND: Horseshoe kidney (HK) with renal stones is challenging for urologists. Although both retroperitoneal and transperitoneal laparoscopic approaches have been reported in some case reports, the therapeutic outcome of retroperitoneal compared with transperitoneal laparoscopic lithotripsy is unknown. AIM: To assess the efficacy of laparoscopic lithotripsy for renal stones in patients with HK. METHODS: This was a retrospective study of 12 patients with HK and a limited number (n ≤ 3) of 20-40 mm renal stones treated with either retroperitoneal or transperitoneal laparoscopic lithotripsy (June 2012 to May 2019). The perioperative data of both groups were compared including operation time, estimated blood loss, postoperative fasting time, perioperative complications and stone-free rate (SFR). RESULTS: No significant difference was observed for age, gender, preoperative symptoms, body mass index, preoperative infection, hydronephrosis degree, largest stone diameter, stone number and isthmus thickness. The mean postoperative fasting time of the patients in the retroperitoneal group and the transperitoneal group was 1.29 ± 0.49 and 2.40 ± 0.89 d, respectively (P = 0.019). There was no significant difference in operation time (194.29 ± 102.48 min vs 151.40 ± 39.54 min, P = 0.399), estimated blood loss (48.57 ± 31.85 mL vs 72.00 ± 41.47 mL, P = 0.292) and length of hospital stay (12.14 ± 2.61 d vs 12.40 ± 3.21 d, P = 0.881) between the retroperitoneal and transperitoneal groups. All patients in both groups had a complete SFR and postoperative renal function was within the normal range. The change in estimated glomerular filtration rate (eGFR) from the preoperative stage to postoperative day 1 in the retroperitoneal group and the transperitoneal group was -3.86 ± 0.69 and -2.20 ± 2.17 mL/(min·1.73 m2), respectively (P = 0.176). From the preoperative stage to the 3-mo follow-up, the absolute change in eGFR values for patients in the retroperitoneal group and the transperitoneal group was -3.29 ± 1.11 and -2.40 ± 2.07 mL/(min·1.73 m2), respectively (P = 0.581). CONCLUSION: Both retroperitoneal and transperitoneal laparoscopic lithotripsy seem to be safe and effective for HK patients with a limited number of 20-40 mm renal stones.

Highly tunable nonlinear response of Au@WS2 hybrids with plasmon resonance and anti-Stokes effect.

We synthesize Au@WS2 hybrid nanobelts and investigate their third-order nonlinear responses mediated by a strong anti-Stokes effect. By using the femtosecond Z-scan technique and tuning the excitation photon energy (Eexc), we find the sign reversals of both nonlinear absorption coefficient ß and nonlinear refractive index γ to be around 1.60 eV, which is prominently higher than the bandgap (1.35 eV) of WS2 bulk owing to the strong anti-Stokes processes around the bandgap of the indirect semiconductors. The saturable absorption and self-defocusing of the WS2 nanobelts are significantly enhanced by the plasmon resonance of the Au nanoparticles when Eexc > 1.60 eV. But the excited state absorption assisted by the anti-Stokes processes and the self-focusing observed at Eexc < 1.60 eV are suppressed by the surface plasmon. Furthermore, by using population rate equations, we theoretically analyze the sign reversals of both ß and γ and reveal the physical mechanism of the unique nonlinear responses of the hybrids with the plasmon resonance and anti-Stokes effect. These observations enrich the understanding of the nonlinear processes and interactions between the plasmon and exciton and are helpful for developing nonlinear optical nanodevices.

Early Unclamping Laparoscopic Partial Nephrectomy for Complex Renal Tumor: Data from a Chinese Cohort.

OBJECTIVE: To evaluate the efficacy and safety of early unclamping laparoscopic partial nephrectomy (LPN) for complex renal tumor relative to the standard artery clamping technique (SCT). METHODS: Sixty-one patients with complex renal tumor (RENAL score ≥7) underwent LPN at our institution from January 2013 to April 2017. LPN was performed via SCT in 32 patients and via the early unclamping technique (EUT) in 29 patients. Operation time, warm ischemia time (WIT), blood loss, bleeding requiring transfusion, tumor volume, excisional volume loss (EVL), complications, and renal function before and after operation of the affected kidney were compared between the groups. RESULTS: All surgeries were successful without conversion to open or nephrectomy. EUT reduced the WIT (p < 0.001) but did not increase the complication rate (p = 0.322). Although the tumor volume and EVL were larger in the EUT than in the SCT group (p = 0.011, p = 0.001), glomerular filtration rate (GFR) reduction in the affected kidney did not significantly differ between the groups (p = 0.120). CONCLUSION: Early unclamping LPN for complex renal tumor is safe and efficient. Additionally, the EUT could expand the application of LPN in complex renal tumors, and make this challenging surgery easier and safer.

Curcumin inhibits bladder cancer stem cells by suppressing Sonic Hedgehog pathway.

Cancer stem cells (CSCs) is responsible for the recurrence of human cancers. Thus, targeting CSCs is considered to be a valid way for human cancer treatment. Curcumin is a major component of phytochemicals that exerts potent anticancer activities. However, the effect of curcumin on bladder cancer stem cells (BCSCs) remains to be elucidated. In this study, we investigated the mechanism of curcumin suppressing bladder cancer stem cells. In this study, UM-UC-3 and EJ cells were cultured in serum-free medium (SFM) to form cell spheres that was characterized as BCSCs. Then cell spheres were separately treated with different concentrations of curcumin and purmorphamine. Cell cycle analysis were used to determine the percentage of cells in different phases. Western blot and quantitative real-time PCR analysis were used to detect the expression of relative molecules. Immunofluorescence staining analysis were also utilized to measure the protein level of CD44. We found that CSC markers, including CD44, CD133, ALDH1-A1, OCT-4 and Nanog, were obviously highly expressed in cell spheres. Moreover, we observed that curcumin reduced the cell spheres formation, decreased the expression of CSC markers, suppressed cell proliferation and induced cell apoptosis. We also found that curcumin inhibited the activation of Shh pathway, while the inhibitory effects of curcumin on BCSCs could be weakened by upregulation of Sonic Hedgehog (Shh) pathway. Altogether, these data suggested that curcumin inhibited the activities of BCSCs through suppressing Shh pathway, which might be an effective chemopreventive agent for bladder cancer intervention.

Curcumin reverses benzidine-induced epithelial-mesenchymal transition via suppression of ERK5/AP-1 in SV-40 immortalized human urothelial cells.

Overexposure to benzidine has been manifested as an important cause of bladder cancer. However, the molecular mechanism of benzidine-induced malignancy is still insufficiently interpreted. Epithelial-mesenchymal transition (EMT) is a crucial pathophysiological process in embryonic development as well as initiation and development of epithelium-originated malignant tumors. The role of extracellular regulated protein kinase 5 (ERK5) in benzidine-meditated bladder cancer development has not been explored. In the present study, we explored the role of ERK5/AP-1 pathway in benzidine-induced EMT in human normal urothelial cells and the intervention effect of curcumin on bezidine-induced EMT. We found that benzidine-induced EMT in SV-40 immortalized human urothelial cells (SV-HUC-1) at low concentrations. We detected that ERK5/AP-1 pathway was notably activated. Specific ERK5 inhibitor, XMD8-92 was applied to determine the role of ERK5 in benzidine-induced EMT. Results indicated that XMD8-92 reversed the EMT process. Furthermore, curcumin effectively attenuated benzidine-induced urocystic EMT by suppressing ERK5/AP-1 pathway. In conclusion, the present study revealed the positive role of ERK5/AP-1 in benzidine-provoked urocystic EMT and the curcumin promising use in bladder cancer prevention and intervention via ERK5/AP-1 pathway.

Cigarette smoke extract induces epithelial-mesenchymal transition of human bladder cancer T24 cells through activation of ERK1/2 pathway.

Bladder cancer is a common genitourinary malignant disease worldwide. Abundant evidence has shown that cigarette smoke (CS) is a crucial risk factor for bladder cancer. Nevertheless, the mechanism underlying the relationship between cigarette smoking and bladder cancer remains unclear. In the present study, we investigated the effects of cigarette smoke extract (CSE) on mitogen-activated protein kinase (MAPK) pathway activation and EMT alterations in human bladder cancer T24 cells, and the preventive effect of extracellular regulated protein kinases 1 and 2 (ERK1/2) inhibitor U0126 was further examined. Our results illustrated that CSE exposure induced morphological change of human bladder cancer T24 cells, enhanced migratory and invasive capacities, reduced epithelial marker expression and elevated mesenchymal marker expression. Meanwhile, exposure of T24 cells to CSE resulted in activation of ERK1/2 pathway as well as activator protein 1 (AP-1) proteins. Interestingly, treatment with ERK1/2 inhibitor U0126 effectively abrogated CSE-triggered EMT and ERK1/2/AP-1 activation. These findings provide novel insight into the molecular mechanisms of CS-associated bladder cancer and may open up new avenues in the search for potential target of bladder cancer intervention.