Theaflavin pretreatment ameliorates renal ischemia/reperfusion injury by attenuating apoptosis and oxidative stress in vivo and in vitro.

Oxidative stress-induced apoptosis is an important pathological process in renal ischemia/reperfusion injury (RIRI). Theaflavin (TF) is the main active pigment and polyphenol in black tea. It has been widely reported because of its biological activity that can reduce oxidative stress and protect against many diseases. Here, we explored the role of theaflavin in the pathological process of RIRI. In the present study, the RIRI model of 45 min ischemia and 24 h reperfusion was established in C57BL/6 J male mice, and theaflavin was used as an intervention. Compared with the RIRI group, the renal filtration function, renal tissue damage and antioxidant capacity of the theaflavin intervention group were significantly improved, while the level of apoptosis was reduced. TCMK-1 cells were incubated under hypoxia for 48 h and then reoxygenated for 6 h to simulate RIRI in vitro. The application of theaflavin significantly promoted the translocation of p53 from cytoplasm to nucleus, upregulated the expression of glutathione peroxidase 1 (GPx-1) in cells, and inhibited oxidative stress damage and apoptosis. Transfection with p53 siRNA can partially inhibit the effect of theaflavin. Thus, theaflavin exerted a protective effect against RIRI by inhibiting apoptosis and oxidative stress via regulating the p53/GPx-1 pathway. We conclude that theaflavin has the potential to become a candidate drug for the prevention and treatment of RIRI.

[Risk Management Analysis of Medical Device Registration Self-inspection].

Through the analysis of laws and policies related to registration self-inspection, visiting and researching enterprises, holding symposiums, and issuing nationwide questionnaires, the risks in the registration self-inspection process were summarized, analyzed, and evaluated. From the aspects of regulatory departments and manufacturing enterprises, we suggest to improve China's medical device registration regulations system and reduce the risks of all parties in the registration self-inspection work.

Application of Suctioning Ureteral Access Sheath during Flexible Ureteroscopy for Renal Stones Decreases the Risk of Postoperative Systemic Inflammatory Response Syndrome.

Purpose: To clarify the efficiency and outcomes of suctioning ureteral access sheath (UAS) during flexible ureteroscopic lithotripsy (fURL) for the management of renal stones. Methods: Between January 2017 and January 2019, a total of 444 patients with renal stones undergoing fURL were divided into suctioning UAS and nonsuctioning UAS groups. The outcomes of patients in both groups were compared using a matched-pair analysis (1 : 1 scenario). Furthermore, a directed acyclic graph (DAG) was drawn to guide the multivariate logistic regression model and analyze the protective effect of suctioning UAS on the incidence of postoperative systemic inflammatory response syndrome (SIRS). Results: Before propensity score matching, significant differences were observed between the two groups in blood white cell counts, urine white cell counts, preoperative fever, preoperative indwelling stents, and laterality (P < 0.05). Eighty-one patients in the suctioning UAS group were successfully matched with 81 patients in the nonsuctioning group. The stone-free rate (SFR) on postoperative day 1 after fURL in the suctioning group was higher than that in the nonsuctioning group (86.4% vs. 71.6%; P=0.034), whereas it was comparable between the two groups 1 month after the surgery (88.9% vs. 82.7%; P=0.368). The incidence of postoperative fever or SIRS was lower in the suctioning group (fever: 3.70% vs. 14.8%; P=0.030; SIRS: 1.23% vs. 12.3%; P=0.012). However, the operative duration was similar in both groups (mean (SD)) (72.9 (28.1) min vs. 80.0 (29.5) min; P=0.121). The result of the multivariate logistic regression model guided by DAG revealed that the application of nonsuctioning UAS (odds ratio: 5.28 [1.38-35.07], P=0.034) during fURL was associated with postoperative SIRS. Conclusions: The application of suctioning UAS during fURL was associated with higher SFR on day 1 after surgery and a lower incidence of postoperative fever or SIRS.

Impact of Treatment Modalities on Prognosis in Patients With Renal Collecting Duct Carcinoma: A Population-Based Study.

Objective: Renal collecting duct carcinoma (CDC) is an extremely rare disease with few studies, and the current understanding of its prognosis is limited. We used the Surveillance, Epidemiology, and End Results (SEER) registry data to explore the prognostic factors and effect of treatment modalities on the overall survival (OS) and cancer-specific survival (CSS) in patients with CDC. Methods: Patients' information of CDCs diagnosed by pathological examination between 2000 and 2018 was extracted from the SEER database. The Kaplan-Meier method was used to calculate OS and CSS and log-rank tests to evaluate the differences in OS and CSS. The associations between clinicopathological variables and survival outcomes were assessed with the Cox proportional hazard model. A directed acyclic graph (DAG) was drawn to recognize confounding factors and to obtain the multivariable regression model, and the impact of surgery, radiotherapy, and chemotherapy on OS and CSS was analyzed, respectively. Results: A total of 242 patients with CDC were enrolled. The median OS and CSS time were 17 and 21 months, respectively. The OS rates at 1, 2, and 5 years were 56.9%, 41.9%, and 30.0%, respectively, while the CSS rates at 1, 2, and 5 years were 60.1%, 47.5%, and 34.8%, respectively. Patients who had a large tumor size, poor pathological grade, and advanced TNM classification exhibited worse survival outcomes. Univariable and multivariable Cox regression analyses revealed that surgery, chemotherapy, T stage, N stage, and M stage were independent prognostic factors for OS and CSS. The DAG-guided multivariate Cox regression model revealed that surgery and chemotherapy improved OS and CSS. Conclusions: CDC is an exceedingly rare disease and has malignant behavior. Most patients have a high pathological grade and advanced TNM stage at diagnosis and exhibited poor survival. Resection of all visible tumors including metastatic lesions or chemotherapy can be beneficial to prognosis, while healthier benefits are less likely to receive radiotherapy. More relevant studies with larger samples are needed to verify the value of surgery and adjuvant therapy in the treatment of CDCs.

Green Space Cooling Effect and Contribution to Mitigate Heat Island Effect of Surrounding Communities in Beijing Metropolitan Area.

With the rapid process of urbanization and global warming, many metropolises are vulnerable to high temperatures in summer, threatening the health of residents. However, green spaces can generate a cooling effect to mitigate the urban heat island effect in big cities. They can also help to improve the living quality and wellbeing of surrounding residents. In this paper, we utilized the radiative transfer equation algorithm, k-means clustering algorithm, big data crawling, and spatial analysis to quantify and map the spatial distribution, cooling capacity, and cooling contribution for surrounding communities of 1,157 green spaces within Beijing Fifth Ring Road, a typical metropolitan area. The findings showed that (1) the area proportion of the heat island in the study area is larger than that of the cooling island. Accounting for only about 30% area in the study area, the green spaces reduce the average land surface temperature by 1.32°C. (2) The spatial features of green space, such as area and shape complexity, have a significant influence on its cooling effect. (3) Four clusters of green spaces with specific spatial features and cooling capacity were identified. And there were differences among these clusters in green space cooling contribution for the surrounding communities. (4) The differences in green space cooling contribution also existed in different urban zones. Specifically, the middle zone performed significantly better than the inner and outer zones. (5) We furthered in finding that some green spaces with medium and high cooling contributions need to improve their cooling capacity soon, and some green spaces with low cooling contributions or no contributions have a good potential for constructing new communities in the future. Our study could help planners and government understand the current cooling condition of green spaces, to improve their cooling capacity, mitigate the urban heat island effect, and create a comfortable and healthy thermal environment in summer.

The role of reactive oxygen species derived from different NADPH oxidase isoforms and mitochondria in oxalate-induced oxidative stress and cell injury.

Hyperoxaluria is a risk factor for urolithiasis and can cause renal epithelial cell injury secondary to oxidative stress. Reactive oxygen species (ROS) produced during cell damage originate from different sources and play different roles. Here, we explored the potential sources of ROS production and investigated the role of ROS from various sources in oxalate-induced oxidative stress and cell injury in normal rat kidney-52 epithelial (NRK-52E) cells. Oxalate-induced injury was assessed by lactate dehydrogenase (LDH) release experiments. 2,7-dichlorodihydrofluorescein diacetate and mitoSOX Red were used to determine the intracellular and mitochondrial ROS (mtROS) production, respectively. The expression level of Nox4, Nox2, and p22 protein was detected by Western blotting to observe the effect of oxalate on nicotinamide adenine dinucleotide phosphate oxidase (NADPH) oxidase (Nox). Furthermore, a specific NADPH oxidase subtype inhibitor and targeted mitochondrial antioxidants were used to preliminarily identify the role of ROS from different sources in renal tubular epithelial cell injury induced by oxalate. We found that oxalate inhibited cell viability, induced LDH release, and prompted intracellular and mitochondrial ROS (mtROS) production. Oxalate also decreased the protein expression level of Nox4 and increased the protein expression level of p22. Mitochondria were also a source of ROS production. In addition, Nox2 inhibitor or mtROS scavenging prevented oxalate-induced cell injury, reversed by an inhibitor of Nox4/1. We concluded that ROS from different sources might play different roles in oxalate-induced renal tubular epithelial cell injury. We also identified new potential targets for preventing or alleviating oxalate-induced renal tubular epithelial cell injury.

The Effect of Lactiplantibacillus plantarum BX62 Alone or in Combination with Chitosan on the Qualitative Characteristics of Fresh-Cut Apples during Cold Storage.

In order to explore whether beneficial lactic acid bacteria (LAB) could prolong the shelf life and improve the quality of fresh-cut apples, Lactiplantibacillus plantarum BX62, which was isolated from traditional fermented yak yogurt, and chitosan (CT), were applied to fresh-cut apples, subsequently stored at 4 °C. On days 0, 2, 4, 6, and 8, apple slices were taken for physicochemical, microbiological analysis, and sensory evaluation. The results showed that apple slices coated with L. plantarum BX62 (8 log CFU/mL) presented lower weight loss and browning rate, higher DPPH scavenging capacity, and achieved more effective inhibition of polyphenol oxidase (PPO) and peroxidase (POD) activities compared to the control samples. The application of CT alone or in combination with L. plantarum BX62 resulted in a significant reduction in aerobic mesophilic bacteria (AMB), aerobic psychrophilic bacterial (APB), yeast and molds (YAMs) counts (2.31 log CFU/g for AMB, 2.55 for APB, and 1.58 for YAMs). In addition, L. plantarum BX62 coated apples showed acceptable sensory properties in terms of color, flavor, taste, texture, and overall visual quality during 8 d of storage. On this basis, L. plantarum BX62 could be used as an excellent bio-preservative to extend the shelf life and improve the quality of fresh-cut apples.

Erratum: HIF-1α promotes ZEB1 expression and EMT in a human bladder cancer lung metastasis animal model.

[This corrects the article DOI: 10.3892/ol.2018.7764.].

Theaflavin ameliorates renal ischemia/reperfusion injury by activating the Nrf2 signalling pathway in vivo and in vitro.

Studies have demonstrated that oxidaive stress-induced apoptosis may be the main pathogenic mechanism of renal ischemia/reperfusion (I/R) injury. Theaflavin, a polyphenolic compound extracted from black tea, has been proven to exert strong antioxidant biological function. The objective of the present study was to investigate the potential role of theaflavin on renal I/R injury and its potential molecular mechanism both in vitro and in vivo. C57/BL6 J mice were used to create a model of I/R injury wherein mice were ligated with bilateral renal pedicles for 45 min, and then reperfused for 24 h. A hypoxia/reoxygenation (H/R) model of TCMK-1 cells was used to simulate I/R in vitro. Theaflavin were administered to the treatment group first and then established the model. Kidney Injury Molecule-1 (KIM-1), serum creatinine, urea nitrogen, and 24-h urinary protein levels were evaluated and changes in mitochondrial membrane potential and the ultrastructure of mitochondria were observed. Cell viability, oxidative stress damage, and apoptosis were assessed. The expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream target genes HO-1 and NQO1 were evaluated. Our results revealed that pretreatment with theaflavin significantly inhibited I/R- and H/R-induced renal injury and cell apoptosis. Theaflavin improved mitochondrial dysfunction by attenuating mitochondrial damage and promoting mitochondrial membrane potential. Theaflavin pretreatment significantly reduced malondialdehyde content, while enhancing superoxide dismutase activity in vivo and in vitro. It also reduced oxidative stress and apoptosis mainly by upregulating Nrf2 and its downstream targets in TCMK-1 cells. Thus, theaflavin exerted a protective effect against renal I/R injury by inhibiting oxidative stress and apoptosis via activation of the Nrf2-NQO1/HO-1 pathway as well as correcting mitochondrial dysfunction, thereby presenting its potential as a clinical therapeutic in cases of acute kidney injury.

Management of recurrent ureteral stricture: a retrospectively comparative study with robot-assisted laparoscopic surgery versus open approach.

BACKGROUND: Management of recurrent ureteral stricture is challenging. Consensus on the best surgical choice has not been demonstrated. In this study, we aim to report our experience in treating recurrent ureteral stricture and demonstrate whether robot-assisted procedure for redo ureteral surgery is as effective as open procedure while remaining less invasive. METHODS: We retrospectively assessed 41 patients (22 robot-assisted surgeries and 19 open surgeries) who underwent consecutive robot-assisted and open procedures for redo ureteral surgery from January 2014 to 2018 in our institution. Perioperative outcomes, including demographics, operative time, estimated blood loss, complications, pain scores, success rate and cost, were compared between two groups. RESULTS: There was no significant intergroup difference in terms of age, body mass index, gender composition and American Society of Anesthesiologists scores. A total of 31 patients underwent redo pyeloplasty and ten underwent redo uretero-ureterostomy. Compared with open group, robot-assisted group showed shorter operative time (124.55 min vs. 185.11 min, p < 0.0001), less estimated blood loss (100.00 mL vs. 182.60 mL, p = 0.008) and higher cost (61161.77¥ vs. 39470.79¥, p < 0.0001). Complication rate and pain scores were similar between two groups. Median follow-up periods were 30 and 48 months for robot-assisted and open group respectively. Success rate in the robot-assisted (85.71%) and the open group (82.35%) was not significantly different. CONCLUSIONS: Robot-assisted surgery for recurrent stricture after previous ureteral reconstruction is as effective as open procedure and is associated with shorter operative time and less estimated blood loss.

Inhibiting inflammation and modulating oxidative stress in oxalate-induced nephrolithiasis with the Nrf2 activator dimethyl fumarate.

Hyperoxaluria induces oxidative stress, and inflammation causes renal epithelial cell injury in nephrolithiasis, suggesting that reduced oxalate toxicity may be beneficial. This study aimed to investigate whether nuclear factor (erythroid-derived 2)-like 2 (Nrf2, also called Nfe2l2) induced by dimethyl fumarate (DMF) could protect renal epithelial cells against oxalate-mediated injury both in vivo and in vitro. Glyoxylic acid monohydrate was intraperitoneally injected into Sprague-Dawley rats with or without intragastric administration of DMF. We showed that calcium oxalate crystallisation, accompanied by overexpression of oxidant species and inflammatory cytokines and apoptosis in the rat kidney, was partially reversed by treatment with DMF. Furthermore, oxalate induced a reduction in cell viability, cell damage, oxidant species overexpression, mitochondrial dysfunction, and apoptosis in normal rat kidney epithelial-like (NRK-52E) cells, which were reversed by DMF. Pretreatment of NRK-52E cells with DMF significantly increased Nrf2 levels in the nucleus, with subsequent inhibition of the expression of the nicotinamide adenine dinucleotide phosphate subunits Nox4 and P22, canonical inflammation, and osteogenesis-associated differentiation of target genes in the cytoplasm. This effect was partially inhibited by transfection with Nrf2 siRNA and strengthened by transfection with Kelch-like ECH-associated protein 1 siRNA. These results suggest that DMF exerts beneficial effects in nephrolithiasis by inhibiting inflammation and modulating oxidative stress via regulation of Nrf2.

High Concentration of Calcium Promotes Mineralization in NRK-52E Cells Via Inhibiting the Expression of Matrix Gla Protein.

OBJECTIVE: To address whether matrix Gla protein (MGP) can inhibit mineralization in normal rat kidney tubular cells (NRK-52E) under high concentration of calcium. MATERIALS AND METHODS: NRK-52E cells were treated with high concentration of calcium. The viability and apoptosis of cells were detected by cell counting kit-8 and flow cytology, respectively. Real-time-polymerase chain, Western blotting, and immunofluorescence analysis were conducted to detect the expression of MGP. Cells were transfected with plasmid-MGP or siRNA-MGP for up- or down-regulation of the expression of MGP, respectively. Rat recombinant MGP was also used as supplementation of exogenous MGP. Alizarin red staining was conducted to detect the adherent and deposition of calcium salt. RESULTS: High concentration of calcium suppressed MGP expression in NRK-52E cells. There was significant mineralization when NRK-52E cells were treated with high concentration of calcium. Supplementation with exogenous rat recombinant MGP and overexpression of endogenous MGP both decreased the adherent and deposition of calcium salt to NRK-52E cells, while silence of MGP showed reverse results. CONCLUSION: MGP plays an inhibitory role in the stone formation. However, high concentration of calcium significantly inhibits the expression of MGP and then promotes mineralization in NRK-52E cells.

Losartan Ameliorates Calcium Oxalate-Induced Elevation of Stone-Related Proteins in Renal Tubular Cells by Inhibiting NADPH Oxidase and Oxidative Stress.

Calcium oxalate (CaOx) is the most common type of urinary stone. Increase of ROS and NADPH oxidase gives rise to inflammation and injury of renal tubular cells, which promotes CaOx stone formation. Recent studies have revealed that the renin-angiotensin system might play a role in kidney crystallization and ROS production. Here, we investigated the involvement of Ang II/AT1R and losartan in CaOx stone formation. NRK-52E cells were incubated with CaOx crystals, and glyoxylic acid-induced hyperoxaluric rats were treated with losartan. Oxidative stress statuses were evaluated by detection of ROS, oxidative products (8-OHdG and MDA), and antioxidant enzymes (SOD and CAT). Expression of NADPH oxidase subunits (Nox2 and Nox4), NF-κB pathway subunits (p50 and p65), and stone-related proteins such as OPN, CD44, and MCP-1 was determined by Western blotting. The results revealed upregulation of Ang II/AT1R by CaOx treatment. CaOx-induced ROS and stone-related protein upregulation were mediated by the Ang II/AT1R signaling pathway. Losartan ameliorated renal tubular cell expression of stone-related proteins and renal crystallization by inhibiting NADPH oxidase and oxidative stress. We conclude that losartan might be a promising preventive and therapeutic candidate for hyperoxaluria nephrolithiasis.

HIF-1α promotes ZEB1 expression and EMT in a human bladder cancer lung metastasis animal model.

Lung is one of the most common sites for bladder cancer to metastasize. Although the involvement of the epithelial-to-mesenchymal transition (EMT) in bladder cancer progression has been established, the mechanism of EMT induction remains unclear. In order to investigate this, T24-parental (P) and T24-lung (L) bladder cancer cells were obtained from primary tumors and lung metastatic sites of an animal model with orthotopic spontaneous metastatic bladder cancer, according to a protocol previously described. Compared with T24-P cells, mesenchymal-like T24-L cells exhibited an increased ability in tumor invasion and metastasis, as well as an increased expression of hypoxia-inducible factor (HIF)-1α, zinc finger E-box-binding homeobox 1 (ZEB1), vimentin and N-cadherin and lower level of cytokeratin 18 were observed. Mechanistically, it was identified that HIF-1α increases ZEB1 expression and subsequently regulates the expression of EMT-related genes in both HIF-1α knocking down by siRNA and gain-in HIF-1α by hypoxia culture cell models. In addition, the expression of HIF-1α and ZEB1 in bladder cancer tissues were increased compared with normal bladder epithelial tissues, as well as significantly increased in the high-grade, invasive and metastatic bladder cancer tissues compared with low-grade, superficial and non-metastatic bladder cancer tissues by using immune-histochemical staining assay. Notably, the protein level of HIF-1α was positively associated with that of ZEB1 in bladder cancer tissues. Results from the present study indicate that HIF-1α promotes ZEB1 expression and EMT in the T24-L human bladder cancer lung metastasis animal model, suggesting that HIF-1α serves an important function in the metastasis of bladder cancer, and HIF-1α and ZEB1 may be potential targets for inhibiting bladder metastasis in the future.

[Knock-down of DAB2 interacting protein (DAB2IP) promotes proliferation and inhibits apoptosis of bladder cancer cells].

Objective To study the expression of DAB2 interacting protein (DAB2IP) in human bladder cancer tissues and analyze its relationship with pathological grade and clinical stage, and observe its role in drug resistance of bladder cancer cells. Methods The expression of DAB2IP in primary and recurrent bladder cancers was detected by immunohistochemical staining. RNA interference (RNAi) technique was used to down-regulate the expression of DAB2IP in 5637 and 253J bladder cancer cells. MTT assay and clone formation assay were performed to test the sensitivity of cancer cells to pirarubicin. Flow cytometry was done to detect the apoptosis rate of low-DAB2IP-expressing cells treated with pirarubicin. Results The expression of DAB2IP was negatively correlated with TNM stage, pathological grade and lymph node metastasis of bladder cancer. The expression of DAB2IP in the recurrent bladder cancer was lower than that in the primary bladder cancer. The low expression of DAB2IP in bladder carcinoma cells was related to drug resistance. Knock-down of DAB2IP enhanced the colony formation of bladder cancer cells, reduced the expressions of PARP and caspase-3, increased expressions of Bcl-2 and Mcl-1, reduced the apoptosis of cancer cells and induced chemotherapy tolerance. Conclusion Knock-down of DAB2IP can promote the proliferation and inhibit the apoptosis of bladder cancer cells, and increase the resistance to chemotherapy.

Association between Circulating Vitamin D Level and Urolithiasis: A Systematic Review and Meta-Analysis.

Many studies compared the serum/plasma 1,25 dihydroxyvitamin D3 (1,25(OH)2D) and 25 hydroxyvitamin D3 (25(OH)D) between people with and without nephrolithiasis, and their results were conflicting. After systematically searching PubMed, Web of Science, The Cochrane Library, CNKI, and the Wanfang Database, we conducted a meta-analysis. Thirty-two observational studies involving 23,228 participants were included. Meta-analysis of these studies showed that of stone formers (SFs), calcium SFs had significantly higher concentrations of 1,25(OH)2D (weighted mean difference (WMD), 10.19 pg/mL; 95% confidence interval (CI), 4.31-16.07; p = 0.0007 and WMD, 11.28 pg/mL; 95% CI, 4.07-18.50; p = 0.002, respectively) than non-stone formers, while the levels of 25(OH)D (WMD, 0.88 ng/mL; 95% CI, -1.04-2.80; p = 0.37 and WMD, -0.63 ng/mL; 95% CI, -2.72-1.47; p = 0.56, respectively) are similar. Compared with controls and normocalciuria SFs, hypercalciuria SFs had increased circulating 1,25(OH)2D (WMD, 9.41 pg/mL; 95% CI, 0.15-18.67; p = 0.05 and WMD, 2.75 pg/mL; 95% CI, -0.20-5.69; p = 0.07, respectively) and markedly higher 25(OH)D (WMD, 5.02 ng/mL; 95% CI, 0.99-9.06; p = 0.01 and WMD, 5.02 ng/mL; 95% CI, 2.14-7.90; p = 0.0006, respectively). Normocalciuria SFs had elevated 1,25(OH)2D level (WMD, 6.85 pg/mL; 95% CI, -5.00-18.71; p = 0.26) and comparable 25(OH)D (WMD, 0.94 ng/mL; 95% CI, -3.55-5.43; p = 0.68). Sensitivity analysis generated similar results. Current evidence suggests that increased circulating 1,25(OH)2D is associated with urinary stones and a higher level of circulating 25(OH)D is significantly associated with hypercalciuria urolithiasis. Further studies are still needed to reconfirm and clarify the role of vitamin D in the pathogenesis of stones.

DAB2IP regulates the chemoresistance to pirarubicin and tumor recurrence of non-muscle invasive bladder cancer through STAT3/Twist1/P-glycoprotein signaling.

There is a high frequency of tumor recurrence in non-muscle invasive bladder cancer (NMIBC) after transurethral resection and postoperative intravesical chemotherapy, however, the molecular mechanisms leading to the chemoresistance and tumor re-growth remain largely unknown. In this study, we observed a significant decrease of DAB2IP expression in high-grade and recurrent NMIBC specimens, which was negatively correlated with Twist1 expression and predicted a lower recurrence-free survival of patients. Mechanistically, DAB2IP could inhibit the phosphorylation and transactivation of STAT3, and then subsequently suppress the expression of Twist1 and its target gene P-glycoprotein, both of which were crucial for the pirarubicin chemoresistance and tumor re-growth of bladder cancer cells. Overall, this study reveals a new promising biomarker modulating the chemoresistance and tumor recurrence of NMIBC after bladder preservation surgery.

[Aberrant expressions of ß-catenin and ZEB1 in bladder cancer and their significance].

OBJECTIVE: To detect the expressions of ß-catenin and zinc finger E-box binding homeobox 1 (ZEB1) in bladder cancer tissues, and analyze their correlation and significance in bladder cancer occurrence and progression. METHODS: The study collected 79 specimens of bladder cancer. EnVision immunohistochemical staining was used to detect the expressions and distribution of ß-catenin and ZEB1 protein. Their correlation was analyzed and their relationship with clinicopathological characteristics was investigated. RESULTS: There was a significant heterogeneity in the expression of ß-catenin in bladder cancer tissues. It might be distributed in the cell membrane, cytoplasm or nucleus. In low-grade clinical and pathological urothelial carcinoma, ß-catenin was mainly expressed in cell membrane and cytoplasm, but in high-grade clinical pathological bladder cancer tissues, it was mostly located in cell cytoplasm and nucleus. ZEB1 in bladder cancer tissues was mainly expressed in cell nucleus, and its expression was elevated with the increased tumor pathological grade and clinical stage. The expressions of the above two proteins were significantly correlated. CONCLUSION: Aberrant expressions of ß-catenin and ZEB1 in bladder cancer tissues are relevant to bladder tumor differentiation and metastasis, and the two expressions are evidently correlated. The two proteins can be simultaneously used as candidate targets for early diagnosis and prognosis prediction.

[DAB2IP expression in bladder transitional cell carcinoma and its correlation with clinical outcome].

OBJECTIVE: To investigate the expression of DAB2IP in bladder transitional cell carcinoma (BTCC) and its correlation with clinical characteristics and prognosis of BTCC patients. METHODS: Immunohistochemical staining was applied to detect DAB2IP protein level in 79 cases of TCCB tissues and 11 cases of normal bladder tissues, and the relationships of the staining results with pathological grade, stage, lymph node metastasis, gender, age and the 3-year survival rate of the patients were analyzed. RESULTS: The expression of DAB2IP in BTCC tissues was significantly lower than that in normal bladder epithelium, and the expression score and rate of DAB2IP in the high-grade, invasive and metastatic BTCC were significantly lower than those in low-grade, superficial and non-metastatic BTCC (P < 0.05). The 3-year survival rate of the patients with high DAB2IP expression was significantly higher than that of the patients with low DAB2IP expression. CONCLUSION: DAB2IP may be one of the important inhibitory factors during the occurrence and progression of BTCC.

2'-hydroxyflavanone inhibits prostate tumor growth through inactivation of AKT/STAT3 signaling and induction of cell apoptosis.

Although there have been advances in therapeutic regimes for metastatic castration-resistant prostate cancer (CRPC), these recent developments have not led to improved cure rates. Thus, more novel agents to prolong patient survival are desired. 2'-Hydroxyflavanone (2HF), a nontoxic natural flavonoid, has been shown to exhibit pleiotropic anticancer effects in many cancer types, including prostate cancer (PCa). However, the therapeutic effects of 2HF on tumor growth and its potential mechanisms in CRPC have not been completely elucidated. In the present study, utilizing three different metastatic and androgen-independent PCa cell models (PC-3, DU145 and C4-2), we found that 2HF treatment not only resulted in inhibition of cell proliferation and colony formation in vitro, but also delayed subcutaneous tumor growth in vivo. Mechanistically, besides its known inhibitory effects on aldo­keto reductase activity and de novo androgen synthesis, 2HF also markedly suppressed AKT phosphorylation, signal transducer and activator of transcription-3 (STAT3) phosphorylation and transactivation subsequently regulating the expression of members of the BCL-2 family (i.e., Mcl-1, Bcl-2 and Bax) and modulating caspase-mediated cell apoptosis. Overall, this study revealed a novel mechanism for 2HF targeting metastatic CRPC, in which inactivation of AKT/STAT3 signaling led to cell apoptosis and growth inhibition.