Comparative Evaluation of Flavor and Sensory Quality of Coffee Pulp Wines.

Coffee pulp wines were produced through the mixed fermentation of Saccharomyces cerevisiae, and the flavor and sensory characteristics were comparatively evaluated. A total of 87 volatile components were identified from five coffee pulp wines, of which 68 were present in all samples, accounting for over 99% of the total concentration. The sample fermented contained significantly higher levels of volatile metabolites (56.80 mg/g). Alcohols (22 species) and esters (26 species) were the main flavor components, with the contents accounting for 56.45 ± 3.93% and 31.18 ± 4.24%, respectively, of the total. Furthermore, 14 characteristic components were identified as potential odor-active compounds, contributing to sweet and floral apple brandy flavor. Although the characteristic components are similar, the difference in the content makes the overall sensory evaluation of the samples different. The samples formed by fermentation of four strains, which obtained the highest score (86.46 ± 0.36) in sensory evaluation, were further interpreted and demonstrated through the Mantel test. The results of the component analysis were effectively distinguished by OPLS-DA and PCA, and this validation was supported by sensory evaluation. The research results provided a technical reference for the production of coffee pulp wines.

Oral mucosal graft ureteroplasty versus ileal ureteric replacement: a meta-analysis.

OBJECTIVES: To describe outcomes of oral mucosal graft ureteroplasty (OMGU) and ileal ureter replacement (IUR) and determine the relative merits of both procedures. METHODS: Databases (including PubMed, Embase and Cochrane) were interrogated for eligible trials that assessed outcomes of OMGU or IUR from 2000 to 30 July 2022. The variables analysed were reconstruction success rates, stricture length, hospital stays, perioperative complications and long-term complications. RESULTS: A total of 23 single-arm studies were included. The pooled reconstruction success rates for OMGU and IUR were 94.9% (95% confidence interval [CI] 91.0%-97.7%) and 85.8% (95% CI 81.0%-90.0%), respectively. Stricture length of patients in the OMGU and IUR groups were 3.73 (95% CI 3.17-4.28) and 11.55 (95% CI 9.82-13.29) cm, respectively. The maximal stricture length repaired by OMGU was 8 cm. The hospital stays were 5.85 (95% CI 3.88-7.82) and 11.55 (95% CI 6.93-16.17) days in the OMGU and IUR groups, respectively. The incidences of low-grade postoperative complications were 13.6% (95% CI 6.9%-20.3%) and 27.3% (95% CI 19.5%-35.1%), high-grade postoperative complications were 4.6% (95% CI 1.8I-8.5%) and 13.0% (95% CI 9.4%-17.1%), and long-term complications (occurred at > 3months) were 9.0% (95% CI 1.7%-20.0%) and 35.4% (95% CI 25.8%-45.6%) in the OMGU and IUR groups, respectively. CONCLUSION: An OMGU is an effective, minimally invasive, and safe alternative to IUR for the management of long ureteric strictures. OMGU was the preferred treatment for long ureteric strictures, especially obstructed ureter segments of ≤8 cm.

CircPTPRA blocks the recognition of RNA N6-methyladenosine through interacting with IGF2BP1 to suppress bladder cancer progression.

BACKGROUND: Circular RNAs (circRNAs) have been found to have significant impacts on bladder cancer (BC) progression through various mechanisms. In this study, we aimed to identify novel circRNAs that regulate the function of IGF2BP1, a key m6A reader, and explore the regulatory mechanisms and clinical significances in BC. METHODS: Firstly, the clinical role of IGF2BP1 in BC was studied. Then, RNA immunoprecipitation sequencing (RIP-seq) analysis was performed to identify the circRNAs interacted with IGF2BP1 in BC cells. The overall biological roles of IGF2BP1 and the candidate circPTPRA were investigated in both BC cell lines and animal xenograft studies. Subsequently, we evaluated the regulation effects of circPTPRA on IGF2BP1 and screened out its target genes through RNA sequencing. Finally, we explored the underlying molecular mechanisms that circPTPRA might act as a blocker in recognition of m6A. RESULTS: We demonstrated that IGF2BP1 was predominantly binded with circPTPRA in the cytoplasm in BC cells. Ectopic expression of circPTPRA abolished the promotion of cell proliferation, migration and invasion of BC cells induced by IGF2BP1. Importantly, circPTPRA downregulated IGF2BP1-regulation of MYC and FSCN1 expression via interacting with IGF2BP1. Moreover, the recognition of m6A-modified RNAs mediated by IGF2BP1 was partly disturbed by circPTPRA through its interaction with KH domains of IGF2BP1. CONCLUSIONS: This study identifies exonic circular circPTPRA as a new tumor suppressor that inhibits cancer progression through endogenous blocking the recognition of IGF2BP1 to m6A-modified RNAs, indicating that circPTPRA may serve as an exploitable therapeutic target for patients with BC.

CircLIFR synergizes with MSH2 to attenuate chemoresistance via MutSα/ATM-p73 axis in bladder cancer.

BACKGROUND: Cisplatin (CDDP) has become a standard-of-care treatment for muscle-invasive bladder cancer (MIBC), while chemoresistance remains a major challenge. Accumulating evidence indicates that circular RNAs (circRNAs) are discrete functional entities. However, the regulatory functions as well as complexities of circRNAs in modulating CDDP-based chemotherapy in bladder cancer are yet to be well revealed. METHODS: Through analyzing the expression profile of circRNAs in bladder cancer tissues, RNA FISH, circRNA pull-down assay, mass spectrometry analysis and RIP, circLIFR was identified and its interaction with MSH2 was confirmed. The effects of circLIFR and MSH2 on CDDP-based chemotherapy were explored by flow cytometry and rescue experiments. Co-IP and Western blot were used to investigate the molecular mechanisms underlying the functions of circLIFR and MSH2. Biological implications of circLIFR and MSH2 in bladder cancer were implemented in tumor xenograft models and PDX models. RESULTS: CircLIFR was downregulated in bladder cancer and expression was positively correlated with favorable prognosis. Moreover, circLIFR synergizing with MSH2, which was a mediator of CDDP sensitivity in bladder cancer cells, positively modulated sensitivity to CDDP in vitro and in vivo. Mechanistically, circLIFR augmented the interaction between MutSα and ATM, ultimately contributing to stabilize p73, which triggered to apoptosis. Importantly, MIBC with high expression of circLIFR and MSH2 was more sensitive to CDDP-based chemotherapy in tumor xenograft models and PDX models. CONCLUSIONS: CircLIFR could interact with MSH2 to positively modulate CDDP-sensitivity through MutSα/ATM-p73 axis in bladder cancer. CircLIFR and MSH2 might be act as promising therapeutic targets for CDDP-resistant bladder cancer.

CircHIPK3 sponges miR-558 to suppress heparanase expression in bladder cancer cells.

Increasing evidences suggest that circular RNAs (circRNAs) exert crucial functions in regulating gene expression. In this study, we perform RNA-seq and identify 6,154 distinct circRNAs from human bladder cancer and normal bladder tissues. We find that hundreds of circRNAs are significantly dysregulated in human bladder cancer tissues. We further show that circHIPK3, also named bladder cancer-related circular RNA-2 (BCRC-2), is significantly down-regulated in bladder cancer tissues and cell lines, and negatively correlates with bladder cancer grade, invasion as well as lymph node metastasis, respectively. Over-expression of circHIPK3 effectively inhibits migration, invasion, and angiogenesis of bladder cancer cells in vitro and suppresses bladder cancer growth and metastasis in vivo Mechanistic studies reveal that circHIPK3 contains two critical binding sites for the microRNA miR-558 and can abundantly sponge miR-558 to suppress the expression of heparanase (HPSE). Taken together, our findings provide evidence that circRNAs act as "microRNA sponges", and suggest a new therapeutic target for the treatment of bladder cancer.

Circular RNA BCRC-3 suppresses bladder cancer proliferation through miR-182-5p/p27 axis.

BACKGROUND: Circular RNAs (circRNAs) are a new member of noncoding RNAs (ncRNAs) that have recently been described as key regulators of gene expression. Our previous study had identified the negative correlation between circHIPK3 and bladder cancer grade, invasion, as well as lymph node metastasis. However, the roles of circRNAs in cellular proliferation in bladder cancer remain largely unknown. METHODS: We had analyzed circRNA high-throughout sequencing from human tissues and determined bladder cancer related circRNA-3 (BCRC-3, GenBank: KU921434.1) as a new candidate circRNA derived from PSMD1 gene. The expression levels of circRNAs, mRNAs and miRNAs in human tissues and cells were detected by quantitative real-time PCR (qRT-PCR). The effects of BCRC-3 on cancer cells were explored by transfecting with plasmids in vitro and in vivo. RNA pull down assay, luciferase reporter assay and fluorescence in situ hybridization were applied to verify the interaction between BCRC-3 and microRNAs. Anticancer effects of methyl jasmonate (MJ) were measured by flow cytometry assay, western blot and qRT-PCR. RESULTS: BCRC-3 was lowly expressed in bladder cancer tissues and cell lines. Proliferation of BC cells was suppressed by ectopic expression of BCRC-3 in vitro and in vivo. Mechanistically, overexpression of BCRC-3 induced the expression of cyclin-dependent kinase inhibitor 1B (p27). Importantly, BCRC-3 could directly interact with miR-182-5p, and subsequently act as a miRNA sponge to promote the miR-182-5p-targeted 3'UTR activity of p27. Furthermore, MJ significantly increased the expression of BCRC-3, resulting in an obvious up-regulation of p27. CONCLUSIONS: BCRC-3 functions as a tumor inhibitor to suppress BC cell proliferation through miR-182-5p/p27 axis, which would be a novel target for BC therapy.

Inhibition of BRD4 Suppresses Cell Proliferation and Induces Apoptosis in Renal Cell Carcinoma.

BACKGROUND/AIMS: Renal cell carcinoma (RCC) remains an intractable genitourinary malignancy. Resistance to chemotherapy or targeted therapies in RCC is presumably due to the complicated underlying molecular mechanisms and insufficient understanding. The aim of this research was to assess the expression and role of bromodomain-4 protein (BRD4) in RCC and evaluate the effects of BRD4 inhibitor JQ1 for RCC treatment. METHODS: BRD4 expressionlevels were assessed by qRT-PCR and western blot in RCC tissues and cells. The effects of BRD4 knockdown or JQ1 on RCC cells were assessed by MTT assay and flow cytometry. The effects of in vivo treatment were evaluated through xenograft experiments. RESULTS: BRD4 is significantly overexpressed in RCC, and is related to tumor stage and lymph node metastasis. Inhibition of BRD4 suppressed RCC cell proliferation, induced cell apoptosis in vitro and repressed tumor growth in vivo. Inhibition of BRD4 decreased BCL2 and C-MYC expression while increased BAX and cleaved caspase3 expression, and strikingly diminished the recruitment of BRD4 to BCL2 promoter. CONCLUSIONS: Our research reveals that BRD4 probably play a critical role in RCC progression, and is a new promising target for pharmacological treatment directed against this intractable disease.

Minimally invasive reconstruction of extensive mid-lower ureteral strictures using a bilateral Boari flap.

Objective: To describe and evaluate the technique using bilateral Boari flap ureteroneocystostomy (BBFUNC) for bilateral mid-lower ureteral strictures. Methods: We retrospectively reviewed five patients who underwent minimally invasive BBFUNC in our institution (Union Hospital, Wuhan, China) between July 2019 and December 2021. The bilateral ureters were mobilized and transected above the stenotic segments. The bladder was isolated and incised longitudinally from the middle of the anterior wall. Then, an inverted U-shaped bladder flap was created on both sides, fixed onto the psoas tendon, and anastomosed to the ipsilateral distal normal ureter. Following double-J stenting, the Boari flaps were tubularized, and the bladder was closed with continuous sutures. The patients' perioperative data and follow-up outcomes were collected, and a descriptive statistical analysis was performed. Results: No case converted to open surgery, and no intraoperative complication occurred. The median surgical time was 230 (range 203-294) min. The median length of the bladder flaps was 6.2 (range 4.3-10.0) cm on the left and 5.5 (range 4.7-10.5) cm on the right side. All patients had not developed recurrent ureteral stenosis during the median follow-up time of 17 (range 16-45) months and had a normal maximum flow rate after surgery. The median post-void residual was 7 (range 0-19) mL. The maximal bladder capacity was decreased in one (20%) patient. Conclusion: The present study demonstrates that minimally invasive BBFUNC is feasible and safe in treating bilateral mid-lower ureteral strictures, and the impact on lower urinary tract function is limited.

Treating Multifocal Ureteral Strictures with Combined Techniques: 14 Cases of Initial Experience.

Purpose: To evaluate the safety and feasibility of lingual mucosal graft ureteroplasty (LMGU) combined with ureteral reimplantation (UR) for repairing managing multifocal ureteral strictures (MUS). Methods: Between December 2020 and December 2022, 14 patients underwent LMGU combined with UR. Their perioperative data were collected retrospectively and analyzed. For the proximal diseased ureter, the narrow segment was incised longitudinally to open the ventral wall of ureter, and a lingual mucosal graft was placed as an onlay graft. Meanwhile, UR was applied to treat distal ureteral strictures. Results: Of 14 patients, three (21.4%) had previously undergone a failed ureteral reconstruction. The mean (standard deviation [SD]) proximal stricture length was 4.0 cm (1.56), and distal ureteral stricture length was 4.3 cm (0.94). The mean (SD) operative time was 236 minutes (57), the estimated blood loss was 78 mL (41.5), and the length of postoperative stay was 6 days. One (7%) patient underwent double LMGU to treat proximal 2 segments of ureteral stricture. No open conversions and intraoperative complications occurred. With a mean follow-up of 15 months (range 6-29), the recurrence-free rate was 14/14 (100%). Conclusions: LMGU combined with UR is a feasible and effective technique for managing MUS and can be an alternative to ileal ureteral replacement or renal autotransplantation in some selected patients with MUS.

The Whitaker test: a predictive tool for evaluating the surgical efficacy of upper urinary tract reconstruction in patients carrying a nephrostomy tube after surgery.

PURPOSE: To explore the role of the Whitaker test in evaluating the postoperative outcome of upper urinary tract reconstruction surgery in patients carrying a nephrostomy tube after surgery. PATIENTS AND METHODS: This was a prospective observational study performed in 42 patients with nephrostomy tube undergoing the Whitaker test after upper urinary tract reconstruction surgery between January 2020 and December 2021. Data on clinical information, the Whitaker test and surgical procedure were collected prospectively, and the long-term follow-up results were analysed retrospectively. RESULTS: The 46 ureters of 42 patients (right 16, left 22, bilateral 4) underwent six common upper urinary tract surgical reconstruction procedures and one combined procedure, including pyeloplasty, ureteroureterostomy, lingual mucosal onlay graft, appendiceal onlay flap, ureteral reimplantation, Boari flap, and ipsilateral lingual mucosal onlay graft combined ureteral reimplantation. All patients underwent the Whitaker test successfully without any discomfort after examination. The postoperative Whitaker test showed 43 kidneys without obstruction and 3 kidneys with obstruction. At a median follow-up of 18 months (range 13-31), the follow-up results showed that the overall success rate of the surgery was 100% (46/46). Concerning the concordance Whitaker test and follow-up results, the observed proportion of agreement was 93.5% (43/46). CONCLUSION: The Whitaker test can achieve similar consistency with the long-term follow-up results after upper urinary tract reconstruction surgery and can be used as a tool to evaluate the surgical efficacy of upper urinary tract reconstruction surgery, which can provide a prognostic efficacy evaluation for patients carrying a nephrostomy tube after surgery.

CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression.

Chromatin accessibility plays important roles in revealing the regulatory networks of gene expression, while its application in bladder cancer is yet to be fully elucidated. Chloride intracellular channel 3 (CLIC3) protein has been reported to be associated with the progression of some tumors, whereas the specific mechanism of CLIC3 in tumor remains unclear. Here, we screened for key genes in bladder cancer through the identification of transcription factor binding site clustered region (TFCR) on the basis of chromatin accessibility and TF motif. CLIC3 was identified by joint profiling of chromatin accessibility data with TCGA database. Clinically, CLIC3 expression was significantly elevated in bladder cancer and was negatively correlated with patient survival. CLIC3 promoted the proliferation of bladder cancer cells by reducing p21 expression in vitro and in vivo. Mechanistically, CLIC3 interacted with NAT10 and inhibited the function of NAT10, resulting in the downregulation of ac4C modification and stability of p21 mRNA. Overall, these findings uncover an novel mechanism of mRNA ac4C modification and CLIC3 may act as a potential therapeutic target for bladder cancer.

Robotic-assisted appendiceal onlay flap ureteroplasty combined with ureteral reimplantation for multifocal ureteral strictures: Case report and technical description.

BACKGROUND: To describe the surgical technique of robotic-assisted appendiceal onlay flap ureteroplasty combined with ureteral reimplantation to repair unilateral multifocal ureteral strictures in one stage and report 9-month follow-up outcomes. METHOD: A longitudinal ventral incision of proximal ureter strictures No. 1 and 2 was performed, and the appendix was detubularised along its antimesenteric border. Then, the appendiceal onlay flap was anastomosed with the spatulated ureter in an onlay fashion. To manage the distal ureteral stricture No. 3, ureteral reimplantation was performed in a tension-free manner. RESULTS: Voiding cystourethrography and antegrade urography showed urine regurgitation into the ureter without dilation and no obstruction of the reconstructed ureteral segment 7 weeks after surgery. No postoperative complications occurred during the 9-month follow-up. CONCLUSIONS: Robotic-assisted appendiceal onlay flap ureteroplasty combined with ureteral reimplantation appears to be a safe and effective surgical method for repairing the unilateral multifocal ureteral strictures.

Robotic-assisted double lingual mucosal graft ureteroplasty for multifocal ureteral strictures: Case report and technical description.

BACKGROUND: Ureteroplasty with a single onlay graft for proximal ureter stricture has been widely used in the clinic. However, robotic ureteroplasty with a double lingual mucosal graft (RU-DLMG) has not been reported. METHODS: The intraoperative measured ureteral stricture lengths of patient 1 were 1.8, 2.5, and 4.6 cm, and those of patient 2 were 2.5 and 3.5 cm. We performed a RU-DLMG in which the diseased ureter was incised longitudinally from the ventral side and repaired with a double lingual mucosal graft to widen the ureteral lumen. Because of the presence of a distal ureter stricture, RU-DLMG combined with ureteral reimplantation was performed in patient 1. RESULTS: Antegrade urography showed no obstruction of the reconstructed ureteral segment after removing the ureteral stent. The patients had no complaints about the donor site and flank pain during the 12-month follow-up. CONCLUSIONS: RU-DLMG appears to be a suitable option for multifocal ureteral strictures.

Correction: Metformin inhibits the proliferation of benign prostatic epithelial cells.

[This corrects the article DOI: 10.1371/journal.pone.0173335.].

Regulation of CD8+ T cells infiltration and immunotherapy by circMGA/HNRNPL complex in bladder cancer.

The limited success of immunotherapies targeting immune checkpoint inhibitors is largely ascribed to the lack of infiltrating CD8+ T lymphocytes. Circular RNAs (circRNAs) are a novel type of prevalent noncoding RNA that have been implicated in tumorigenesis and progression, while their roles in modulating CD8+ T cells infiltration and immunotherapy in bladder cancer have not yet been investigated. Herein, we uncover circMGA as a tumor-suppressing circRNA triggering CD8+ T cells chemoattraction and boosting the immunotherapy efficacy. Mechanistically, circMGA functions to stabilize CCL5 mRNA by interacting with HNRNPL. In turn, HNRNPL increases the stability of circMGA, forming a feedback loop that enhances the function of circMGA/HNRNPL complex. Intriguingly, therapeutic synergy between circMGA and anti-PD-1 could significantly suppress xenograft bladder cancer growth. Taken together, the results demonstrate that circMGA/HNRNPL complex may be targetable for cancer immunotherapy and the study advances our understanding of the physiological roles of circRNAs in antitumor immunity.

ARID1A Inactivation Increases Expression of circ0008399 and Promotes Cisplatin Resistance in Bladder Cancer.

OBJECTIVE: Cisplatin (CDDP)-based chemotherapy is a first-line, drug regimen for muscle-invasive bladder cancer (BC) and metastatic bladder cancer. Clinically, resistance to CDDP restricts the clinical benefit of some bladder cancer patients. AT-rich interaction domain 1A (ARID1A) gene mutation occurs frequently in bladder cancer; however, the role of CDDP sensitivity in BC has not been studied. METHODS: We established ARID1A knockout BC cell lines using CRISPR/Cas9 technology. IC50 determination, flow cytometry analysis of apoptosis, and tumor xenograft assays were performed to verify changes in the CDDP sensitivity of BC cells losing ARID1A. qRT-PCR, Western blotting, RNA interference, bioinformatic analysis, and ChIP-qPCR analysis were performed to further explore the potential mechanism of ARID1A inactivation in CDDP sensitivity in BC. RESULTS: It was found that ARID1A inactivation was associated with CDDP resistance in BC cells. Mechanically, loss of ARID1A promoted the expression of eukaryotic translation initiation factor 4A3 (EIF4A3) through epigenetic regulation. Increased expression of EIF4A3 promoted the expression of hsa_circ_0008399 (circ0008399), a novel circular RNA (circRNA) identified in our previous study, which, to some extent, showed that ARID1A deletion caused CDDP resistance through the inhibitory effect of circ0008399 on the apoptosis of BC cells. Importantly, EIF4A3-IN-2 specifically inhibited the activity of EIF4A3 to reduce circ0008399 production and restored the sensitivity of ARID1A inactivated BC cells to CDDP. CONCLUSION: Our research deepens the understanding of the mechanisms of CDDP resistance in BC and elucidates a potential strategy to improve the efficacy of CDDP in BC patients with ARID1A deletion through combination therapy targeting EIF4A3.

Differentially expressed proteins identified in overexpressed let-7a gastric carcinoma cells by two-dimensional polyacrylamide gel electrophoresis.

MicroRNAs are small noncoding RNA molecules that control the expression of target genes. Our previous studies show that let-7a decreased in gastric carcinoma and that up-regulation of let-7a by gene augmentation inhibited gastric carcinoma cell growth both in vitro and in vivo, whereas it remains largely unclear as to how let-7a affects tumor growth. In this study, proteins associated with the function of let-7a were detected in high-throughput screening. The cell line of SGC-7901 stably overexpressing let-7a was successfully established by gene clone. Two-dimensional gel electrophoresis (2-DE) was used to separate the total proteins of SGC-7901/let-7a, SGC-7901/EV and SGC-7901, and PDQuest software was applied to analyze 2-DE images. Ten differential protein spots were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and they may be the proteins associated with let-7a function. The overexpressed proteins include antioxidant protein 2, insulin-like growth factor binding protein 2, protein disulfide isomerase A2, C-1-tetrahydrofolate synthase, cyclin-dependent kinase inhibitor1 (CDKN1) and Rho-GTPase activating protein 4. The underexpressed proteins consisted of S-phase kinase-associated protein 2 (Spk2), platelet membrane glycoprotein, fibronectin and Cks1 protein. Furthermore, the different expression levels of the partial proteins (CDKN1,Spk2 and Fibronectin) were confirmed by Western blot analysis. The data suggest that these differential proteins are involved in novel let-7a signal pathway, and these findings provided the basis to comprehensively investigate the functional mechanisms of let-7a in gastric carcinoma.

Gambogic acid inhibits TNF-α-induced invasion of human prostate cancer PC3 cells in vitro through PI3K/Akt and NF-κB signaling pathways.

AIM: To investigate the mechanisms underlying the inhibitory effect of gambogic acid (GA) on TNF-α-induced metastasis of human prostate cancer PC3 cells in vitro. METHODS: TNF-α-mediated migration and invasion of PC3 cells was examined using migration and invasion assays, respectively. NF-κB transcriptional activity and nuclear translocation were analyzed with luciferase reporter gene assays, immunofluorescence assays and Western blots. The ability of p65 to bind the promoter of Snail, an important mesenchymal molecular marker, was detected using a chromatin immunoprecipitation (ChIP) assay. After treatment with Snail-specific siRNA, the expression of invasiveness-associated genes was measured using quantitative real-time PCR and Western blot. RESULTS: GA significantly inhibited the viability of PC3 cells at 1-5 µmol/L, but did not produce cytotoxic effect at the concentrations below 0.5 µmol/L. GA (0.125-0.5 µmol/L) dose-dependently inhibited the migration and invasion of PC3 cells induced by TNF-α (10 ng/mL). Moreover, the TNF-α-mediated activation of phosphatidylinositol-3-OH kinase/protein kinase B (PI3K/Akt) and NF-κB pathways was suppressed by GA (0.5 µmol/L). Furthermore, this anti-invasion effect of GA was associated with regulation of Snail. Snail expression was significantly down-regulated by treatment with GA (0.5 µmol/L) in the TNF-α-stimulated PC3 cells. CONCLUSION: GA inhibits TNF-α-induced invasion of PC3 cells via inactivation of the PI3K/Akt and NF-κB signaling pathways, which may offer a novel approach for the treatment of human prostate cancer.