miR-199a/214 cluster enhances prostate cancer sensitiveness to nimotuzumab via targeting TBL1XR1.

Prostate cancer (PCa) is a significant health concern affecting men worldwide. Previous studies have shown that nimotuzumab, a drug targeting the epidermal growth factor receptor (EGFR), can effectively inhibit cancer progression. Here, we aimed to explore the role of miR-199a/214 cluster in mediating the inhibitory effect of nimotuzumab on the development of PCa. In this study, we conducted an MTT assay to assess cell proliferation and utilized flow cytometry to evaluate cell apoptosis and cell cycle arrest. To investigate the molecular mechanisms underlying the effects of nimotuzumab on prostate cancer development, we focused on the miR-199a-5p and miR-214-3p miRNA clusters. The TargetScan Human database was used to predict the binding sites between miR-199a-5p or miR-214-3p and the 3'-UTR of the transducin (ß)-like 1 X-linked receptor 1 (TBL1XR1) mRNA. To confirm the direct interaction and binding between miR-199a-5p or miR-214-3p and the 3'-UTR of TBL1XR1 mRNA, we performed luciferase reporter assays. Our findings demonstrated that nimotuzumab exerted a significant dosage-dependent suppression of PCa cell proliferation and facilitated PCa cell apoptosis and cell cycle arrest. Concurrently, nimotuzumab obviously impeded the activity of Wnt/ß-catenin and EGFR signaling pathways in PCa cells. We also observed downregulation of miR-199a-5p and miR-214-3p in PCa cells. Overexpression of miR-199a/214 cluster inhibited PCa cell viability and enhanced cell apoptosis. Furthermore, we found that miR-199a/214 cluster augmented the inhibitory effect of nimotuzumab on PCa cell proliferation and promoted its ability to induce apoptosis and cell cycle arrest. This effect was reversed upon TBL1XR1 overexpression, indicating that TBL1XR1 is involved in the regulatory pathway of miR-199a/214 and nimotuzumab in PCa cells. We further revealed that TBL1XR1 was overexpressed in PCa and was identified as a downstream target of the miR-199a/214 cluster. In nimotuzumab-treated PCa cells, the overexpression of miR-199a/214 markedly inhibited Wnt/ß-catenin and EGFR signaling, and this effect was also rescued by TBL1XR1 overexpression. In summary, our data indicated that miR-199a/214 cluster play a crucial role in enhancing the inhibitory effect of nimotuzumab on PCa development by downregulating TBL1XR1 and modulating Wnt/ß-catenin and EGFR signaling pathways. These findings offer a novel therapeutic approach for the treatment of prostate cancer.

Combined treatment of impacted ureteral stones: Holmium laser and pneumatic ballistic.

The treatment of impacted stones remains a challenging issue for urologists, and is usually treated clinically by a single surgical procedure. In this paper, we report a case of combined holmium laser and pneumatic ballistics for the treatment of an impacted ureteral stone. The postoperative examination showed that the stone was cleared and no complications occurred.

Exosomal miR-193b-3p Contributes to Cisplatin Sensitivity in Seminoma by Targeting ZBTB7A.

A previous study confirmed that miRNAs play an important role in the chemosensitivity of seminoma. Increasing evidence reveals that exosomes participate in the regulation of cisplatin resistance by carrying miRNAs. In this study, we further explored whether exosomes regulated the chemosensitivity of seminoma TCam-2 cells to cisplatin. Initially, cisplatin-resistant TCam-2 cells were induced. Our results revealed that exosomes from cisplatin-resistant TCam-2 cells (rExos) could affect the viability of TCam-2 cells in the context of cisplatin treatment through regulation of both cell apoptosis and the cell cycle. Meanwhile, the levels of γ-H2AX were negatively modulated by rExos, which indicated that rExos could decrease the DNA damage from cisplatin. Furthermore, miR-193b-3p was enriched in rExos, and exosomal miR-193b-3p enhanced the proliferative ability of TCam-2 cells under cisplatin treatment. Mechanistically, exosomal miR-193b-3p targets ZBTB7A, which further decreases apoptosis and promotes cell cycle progression. Taken together, these findings indicate that exosomal miR-193b-3p regulates the chemosensitivity of TCam-2 cells to cisplatin through ZBTB7A signaling and could be a promising drug target for patients with chemoresistant seminoma.

Laparoscopic treatment of a giant seminal vesicle cyst with hemorrhage: A case report.

RATIONALE: A seminal vesicle cyst is a benign lesion of the seminal vesicle that is usually asymptomatic. However, when a giant seminal vesicle cyst ruptures and bleeds, it can cause obvious clinical symptoms. To our knowledge, no single giant seminal vesicle cyst with hemorrhage has been reported in current studies, and surgery is the primary method to treat seminal vesicle hemorrhage with obvious symptoms. PATIENT CONCERNS: A 31-year-old man presented with urination pain but without obvious urination frequency and urgency, dysuria, and discomfort. Rectal palpation in the chest-knee position revealed a hard mass palpable in the upper right with a smooth surface and mild tenderness, and the upper edge of the mass could not be palpated. DIAGNOSIS: The results of the B-mode ultrasound indicated a mixed echogenic lump between the bladder and prostate, with a size of 81 × 76 mm. The computer tomography scan showed an "S" tubular lump in the right side of the pelvic cavity. The mass has a computer tomography value of 58 to 70 HU, and uneven reinforcement can be observed. On the basis of the results of the magnetic resonance imaging of the urinary bladder, the lump has T1 and T2 signals of equal lengths. INTERVENTIONS: The patient was diagnosed with a huge right seminal vesicle cyst with hemorrhage and was treated via laparoscopic surgery. OUTCOMES: The patient recovered quickly after the operation, and the symptoms of urination pain were significantly improved. LESSONS: Seminal vesicle hemorrhage is clinically rare, and laparoscopic treatment is an effective and safe surgical method for the treatment of seminal vesicle cysts.

Facile synthesis of carboxymethyl cellulose sulfur quantum dots for live cell imaging and sensitive detection of Cr(VI) and ascorbic acid.

Nowadays the synthesis of stable fluorescent sulfur quantum dots (SQDs) remains a big challenge. Herein, the utilization of carboxymethyl cellulose (CMC) to synthesis of SQDs is reported. Benefiting from the unique composition and structure of CMC macromolecule, the resulted CMC-SQDs simultaneously show high aqueous dispersibility and stability, tunable emission, stable fluorescence and low cytotoxicity, which make them promising for working as a fluorescent probe. Fluorescence detection experiments suggested that the CMC-SQDs could serve as a fluorescence on-off-on switch to sensitive and selective detection of Cr(VI) and ascorbic acid (AA) based on the inner filter effect (IFE). The limit of detection towards Cr(VI) and AA can reach 0.024 and 0.18 µM with linear range of 0.5-225 and 1-300 µM, respectively, which compares favorably to other reported fluorescent probes. In addition, the employment of fluorescent CMC-SQDs for practical detection of Cr(VI) and AA was also studied.

ISYNA1 is overexpressed in bladder carcinoma and regulates cell proliferation and apoptosis.

BACKGROUND: Bladder cancer (BCa) is one of the most common urological malignancies. While Inositol-3-phosphate synthase 1 (ISYNA1) expression and function were largely unknown in BCa. We aimed to study the expression and role of ISYNA1 in bladder cancer and investigate its potential mechanisms via ingenuity pathway analysis (IPA). METHODS: ISYNA1 expression was quantified by qRT-PCR in bladder cancer cell lines as well as normal urothelial cell line. Knocking down ISYNA1 gene in BCa T24 cells was achieved by shRNA lentivirus transfection. MTT and Celigo assay were used to assess cell proliferation. Flow cytometry was applied to test cell cycle and apoptosis. In addition, IPA was performed using PrimeView™ Human Gene Expression Array. Imunohistochemistry (IHC) was performed in BCa patient tissue microarray to verify the association between ISYNA1 expression and patients' clinicopathological features. RESULTS: ISYNA1 was significantly upregulated in BCa samples vs. para-tumor tissues. Higher expression were significantly associated with tumor T stage and lymph node metastasis of bladder cancer patients. Similarly, it was elevated in BCa cell lines (5637 and T24) compared with SVHUC cells. Knocking down ISYNA1 significantly decreased proliferation, induced apoptosis and cell cycle arrest in T24 cells. Furthermore, IPA indicated that ISYNA1 was an important regulatory factors and related networks were involved in multiple functional processes. CONCLUSION: Taken together, current study suggest ISYNA1 promotes proliferation and inhibit apoptosis in bladder cancer cells, and its expression correlated with BCa patients' clinicopathological features. Thus, ISYNA1 may serve as a potential biomarker and therapeutic target for BCa patients.

Facile synthesis of polyamidoamine dendrimer gel with multiple amine groups as a super adsorbent for highly efficient and selective removal of anionic dyes.

Preparation of excellent dye adsorbent that simultaneously displays convenient separation capability, high adsorption capacity, fast removal rate, superior adsorption selectivity, and favorable reusability remains a challenge. Herein, we present a simple and feasible one-step method to prepare amine-rich porous polyamidoamine (PAMAM) dendrimer gel adsorbent. The PAMAM gel could be readily separated from water by filtration. The adsorption properties of PAMAM gel was systematically examined by adsorption of anionic methyl orange (MO) and tartrazine (TTZ) dyes. The PAMAM gel exhibited superior adsorption selectivity and removal efficiency towards anionic MO and TTZ dyes. The adsorption process could be completed within around 15 min and presented fine correlation with Langmuir isotherm and pseudo-second-order kinetic models. The maximum adsorption capacity of PAMAM gel towards MO and TTZ was as high as 680.2 mg g-1 and 689.7 mg g-1, respectively. Additionally, the dye-adsorbed PAMAM gel could be readily desorbed in alkaline solution. Considering the simple synthetic process and outstanding adsorption performance of PAMAM gel, this paper provides an effective approach to prepare high-performance anionic dye adsorbents.

Nimotuzumab inhibits epithelial-mesenchymal transition in prostate cancer by targeting the Akt/YB-1/AR axis.

Nimotuzumab is a humanized anti-EGF monoclonal antibody that has been approved for treating different cancers. However, few studies have examined its therapeutic potential in prostate cancer (PC), a most common and highly aggressive malignancy among male population. We used both LNCaP, and PC3 and PC3-AR (androgen receptor) cells as the model system and assessed the effects of nimotuzumab on epithelial-mesenchymal transition (EMT) in vitro and in vivo. The EMT makers were detected by immunohistochemistry, qRT-PCR and Western blot. MTT, wound healing assay, and transwell assay were used to measure cell viability, migration, and invasion, respectively. For mechanistic understanding, we evaluated the significance of Akt/Y-box binding protein-1 (YB-1)/AR axis in nimotuzumab-induced EMT by overexpressing AR, activating Akt using SC79, and/or downregulating YB-1 using siRNA. Nimotuzumab suppressed the xenograft growth from both LNCaP and PC3 cells in vivo, which was associated with reduced EMT. Consistently, nimotuzumab inhibited proliferation, cell-cycle progression, EMT, and migration/invasion, but stimulated apoptosis of both LNCaP and PC3-AR cells in vitro. On the molecular level, nimotuzumab inactivated Akt and YB-1 and reduced the expression of AR. Boosting AR expression in LNCaP and PC3-AR cells antagonized the action of nimotuzumab, at least partially restored EMT, and enhanced the migration/invasion. We also found that Akt was essential for controlling YB-1 activation, and both critical for regulating the levels of AR and EMT-related biomarkers. In this study, we presented our novel findings that by targeting the Akt/YB-1/AR axis, nimotuzumab significantly inhibited EMT of PC cells. Considering that EMT is a critical mechanism contributing to the metastatic spread of cancer cells, nimotuzumab may become a promising therapy for alleviating the malignant progression of PC. © 2019 IUBMB Life, 1-14, 2019.

Multi-carboxylic magnetic gel from hyperbranched polyglycerol formed by thiol-ene photopolymerization for efficient and selective adsorption of methylene blue and methyl violet dyes.

Synthesis of adsorbents that simultaneously possess high adsorption performance and convenient separation characteristic remains a big challenge. Herein, we report a viable strategy to prepare hyperbranched polyglycerol (HPG)-based multi-carboxylic magnetic gel (MMG) based on the thiol-ene click chemistry. The obtained HPG-based MMG adsorbent with porous structure and multiple carboxylic groups not only exhibited fast adsorption rate, superior adsorption capacity, and favorable adsorption selectivity towards cationic dyes (e.g., methylene blue (MB) and methyl violet (MV)) but also presented convenient magnetic separation characteristic. The adsorption data showed nice correlation with pseudo-second-order kinetic model and Langmuir isotherm. The optimal adsorption capacity of HPG-based MMG for MB and MV can reach as high as 458.7 and 400.0 mg g-1, respectively. Moreover, the dye-adsorbed HPG-based MMG could be regenerated in ethanol for reuse without obvious decline of removal efficiency. On the basis of the superior adsorption property of HPG-based MMG, this work offers an effective strategy to prepare advanced adsorbent for dye removal from wastewater.

Notch signaling plays a crucial role in cancer stem-like cells maintaining stemness and mediating chemotaxis in renal cell carcinoma.

BACKGROUND: Cancer stem cells (CSCs) are correlated with the initiation, chemoresistance and relapse of tumors. Notch pathway has been reported to function in CSCs maintenance, but whether it is involved in renal cell carcinoma (RCC) CSCs maintaining stemness remain unclear. This study aims to explore the effect of Notch pathway on stemness of CSCs in RCC and the underlying mechanisms. METHODS: The CD133+/CD24+ cells were isolated from RCC ACHN and Caki-1 cell line using Magnetic-activated cell sorting and identified by Flow cytometry analysis. RT-PCR and immunoblot analyses were used for determining the stemness maker expression. The effect of Notch pathway on function of CSCs was assessed by self-renewal ability, chemosensitivity, invasive and migratory ability tumorigenicity in vivo using soft agar colony formation assay, sphere-forming assay, MTT assay, Transwell assay. RESULTS: Here, we found that the sorted CD133+/CD24+cells possessed elevated stemness maker CTR2, BCL-2, MDR1, OCT-4, KLF4, compared with parental cells, as well as enhanced self-renewal ability, stronger resistance to cisplatin and sorafenib, increased invasion and migration, and higher tumorigenesis in vivo, suggesting the CD133+/CD24+ cells have the stem-like characteristics of CSCs and thus identified as RCC CSCs. Then the enhanced notch1, notch2, Jagged1, Jagged2, DLL1 and DLL4 expression were detected in RCC CSCs and blockage of Notch1 or notch2 using pharmacological inhibitor MRK-003 or its endogenous inhibitor Numb resulted in loss of its stemness features: self-renewal, chemoresistance, invasive and migratory potential, and tumorigenesis in vivo. Moreover, it is confirmed that overexpression of notch1 up-regulated CXCR4 inRCC CSCs and augmented SDF-1-induced chemotaxis in RCC CSCs in vitro, which could be rescued when treatment of CXCR4 inhibitor, suggesting that notch signaling promotes the chemotaxis of RCC CSCs by SDF-1/CXCR4 axis. CONCLUSIONS: Our results provide a new mechanism of RCC CSCs maintaining stemness via notch pathway as well as a potential therapeutic target in human RCC.

Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate cancer cells.

Deoxypodophyllotoxin (DPPT) is extracted and separated from citrus-related plants, including Podophyllum (P.) peltatum, P. pleianthum, P. emodi (also called P. hexandrum) and Diphylleia grayi. DPPT has significant antitumor and antiviral activity. However, due to its strong toxicity and side effects, its use is limited in practical applications. The in vitro antitumor efficacy of DPPT on human prostate cancer (PCa) cells remains to be determined. The present study investigated the anticancer effect of DPPT on human PCa cells and its potential mechanism. The data revealed that DPPT markedly reduced cell proliferation and activated the caspase-3 expression level by an increase in apoptotic cell death in DU-145 cells. In addition, treatment with DPPT markedly downregulated the levels of phosphorylated Akt and activated the p53/B-cell lymphoma 2 associated X protein (Bax)/phosphatase and tensin homolog (PTEN) signaling pathway in DU-145 cells, suggesting that caspase-mediated pathways were involved in DPPT-induced apoptosis. The present study suggested the role of DPPT as a novel chemotherapeutic drug for human PCa, which may function through the Akt/p53/Bax/PTEN signaling pathway.

Downregulation of miR-19a exhibits inhibitory effects on metastatic renal cell carcinoma by targeting PIK3CA and inactivating Notch signaling in vitro.

Metastasis seriously affects the clinical outcome of renal cell carcinoma patients. Despite the approval of several targeted therapies that have led to an improvement in the progression-free survival rate for these patients, advanced and metastatic renal cell carcinoma remains difficult to treat. Recently, microRNAs have been found to play a critical role in the metastatic dissemination of renal cell carcinoma cells. In the present study, we found that miR-19a expression was significantly upregulated in metastatic clear cell renal carcinoma than that in adjacent and primary carcinoma tissues using qPCR and in situ hybridization experiments. In addition, the results were confirmed in renal carcinoma cell lines. miR-19a expression in the cell lines derived from a metastatic site was higher than that in cell lines derived from a primary site. By gain- and loss-of-function experiments, we found that miR-19a acted as an oncogenic miRNA regulating renal cancer cell proliferation, migration and invasion by directly targeting PIK3CA. Furthermore, we also explored the downstream molecules of miR-19a/PIK3CA signaling. We found that Notch signaling was induced by upregulation of miR-19a, and inactivation of Notch signaling attenuated the cell proliferation, migration and invasion promoted by miR-19a. Thus, we provide evidence demonstrating that downregulation of miR-19a may be therapeutically beneficial for metastatic renal carcinoma.

Perceptual conflict-induced late positive complex in a modified Stroop task.

To investigate the functional significance of the late positive complex (LPC) in the Stroop task, the present study recruited 22 participants and had them report the color of words in the classical Stroop task and the rotation state of words in a Rotation judgment task. Color words whose ink color was either congruent (CON) or incongruent (INCON) with the word's meaning were presented in both tasks. Consistent with previous studies, the N450 and LPC were observed in the Stroop task, accompanied by slowed reaction time (RT) in the INCON condition compared with the CON condition. Notably, a larger LPC was observed in the INCON condition than in the CON condition in the Rotation task, while RT and accuracy were comparable between the two conditions. Because the incongruence between ink color and word meaning was independent from the response, and neither influenced accuracy nor RT in the Rotation task, the results suggested that the LPC may have resulted from the perceptual conflict between ink color and word meaning.

[One-stage urethroplasty with pedicled scrotal skin flap for hypospadias].

OBJECTIVE: To summarize the experience in one-stage urethroplasty with pedicled scrotal skin flap for hypospadias, and improve its therapeutic effect. METHODS: We retrospectively analyzed the clinical data of 310 cases of hypospadias (except coronal hypospadias) treated by one-stage urethroplasty with pedicled scrotal skin flap. All the patients were followed up for 6 to 24 months. RESULTS: No postoperative complications were observed except urinary fistula, which occurred in 12.6% of the patients. Postoperative fistula formation was associated with the type of hypospadias, the length of the urethral defect and postoperative comprehensive medication, but not with the stent indwelling time after surgery. Most of the fistulae were located at the base of the penis. CONCLUSION: One-stage urethroplasty with pedicled scrotal skin flap is a simple and effective option for all types of hypospadias except the coronal type, and postoperative treatment is very important.