Allograft inflammatory factor-1 enhances inflammation and oxidative stress via the NF-κB pathway of bladder urothelium in diabetic rat model.

OBJECTIVES: To explore the role of allograft inflammatory factor-1 (AIF-1) both in diabetic rat bladder urothelium and in high-glucose-treated human urothelial cell line (SV-HUC-1). METHODS: Inflammation and oxidative stress (OS) promote diabetic cystopathy (DCP), but the mechanisms are not fully understood. The expression level of AIF-1 in diabetic rat bladder urothelium and in the SV-HUC-1 cells treated with high glucose was detected using tissue immunofluorescence, immunohistochemistry and western blot assays. AIF-1 was knocked down and NF-κB was suppressed with the specific inhibitor BAY 11-7082 in high-glucose-treated SV-HUC-1 cells. RESULTS: High-glucose condition induced AIF-1 upregulation in vivo and in vitro. The up-regulated AIF-1 induced the production of inflammatory factors IL-6 and TNF-α and elevation of ROS. Informatics analysis suggested that NF-κB pathway is implicated in DCP. Through knockdown of AIF-1, we confirmed that AIF-1 simulated NF-κB pathway by enhancing the phosphorylation of IκB (p-IκB) and promoting the translocation of NF-κB p65 from cytoplasm into nucleus. Additionally, High-glucose-induced inflammation in SV-HUC-1 cells was attenuated by the addition of NF-κB inhibitor. CONCLUSIONS: This study provides novel information to understand the molecular regulation mechanisms of AIF-1 in DCP.

AI-enabled image fraud in scientific publications.

Destroying image integrity in scientific papers may result in serious consequences. Inappropriate duplication and fabrication of images are two common misconducts in this aspect. The rapid development of artificial-intelligence technology has brought to us promising image-generation models that can produce realistic fake images. Here, we show that such advanced generative models threaten the publishing system in academia as they may be used to generate fake scientific images that cannot be effectively identified. We demonstrate the disturbing potential of these generative models in synthesizing fake images, plagiarizing existing images, and deliberately modifying images. It is very difficult to identify images generated by these models by visual inspection, image-forensic tools, and detection tools due to the unique paradigm of the generative models for processing images. This perspective reveals vast risks and arouses the vigilance of the scientific community on fake scientific images generated by artificial intelligence (AI) models.

Clinical features and outcomes of adrenal schwannoma: a study of 13 cases from a single centre.

BACKGROUND: Adrenal schwannomas (AS) are extremely rare neoplasms. This study shares our experience regarding the diagnosis and operative management of AS. METHODS: Clinical details, radiologic, laboratory, and pathologic findings as well as follow-up data were analysed retrospectively for 13 AS patients who accepted surgery at a tertiary referral hospital in China between 1 January 1996, and 31 December 2017. RESULTS: The mean age of the patients at diagnosis was 44.7 ± 13.7 years (range 19-62 years; male: female ratio, 1:1.16), of whom seven patients had unilateral AS on the right side, and the remaining six on the left side. None of the cases were hormonally active. None of the 13 cases were diagnosed as AS by CT imaging before the operation. Among the patients, ten were asymptomatic. The mean preoperative size was 7.1 ± 3.2 cm (range 1.6-12.6 cm). All patients underwent surgery, with open adrenalectomy in five patients and laparoscopy in eight patients. The mean tumor size on pathologic examination was 6.8 ± 3.0 cm (range 3.0-11.7 cm). The surgical specimens were confirmed by pathological examination. During a median follow-up of 60.8 ± 17.7 months, no patients showed recurrence or metastasis. CONCLUSION: The preoperative diagnosis of AS remains difficult despite the advances in imaging examinations. After complete resection, the prognosis of AS is excellent.

The effect of miR-124-3p on cell proliferation and apoptosis in bladder cancer by targeting EDNRB.

INTRODUCTION: Endothelin receptor type B (EDNRB) is a potential target gene of miR-124-3p, but the association between miR-124-3p and EDNRB has not yet been reported. The aim of this study was to investigate the role of miR-124-3p in bladder cancer (BC) and to determine whether miR-124-3p regulates cell proliferation by targeting EDNRB. MATERIAL AND METHODS: Bladder cancer tissues and cell lines were obtained in order to analyze the miR-124-3p and EDNRB expression through quantitative RT-PCR (qRT-PCR) and western blotting analysis. The dual-luciferase reporter assay was employed to confirm the relationship between miR-124-3p and EDNRB. The manipulation of miR-124-3p and EDNRB expression was achieved through cell transfection. Cell proliferation and apoptosis were evaluated by MTS assay, colony forming assay and flow cytometry. A nude mouse tumorigenicity assay was used to detect the effects of miR-124-3p in vivo. RESULTS: There was an inverse correlation between the expression of miR-124-3p and EDNRB; miR-124-3p was down-regulated and EDNRB was up-regulated in BC tissues and cell lines. MiR-124-3p was observed to target EDNRB and suppress its expression. Other studies have suggested that the transfection of miR-124-3p mimics and EDNRB siRNA can suppress BC cell proliferation and induce cell apoptosis. CONCLUSIONS: miR-124-3p regulates the proliferation and apoptosis of BC cells by suppressing EDNRB expression.

Downregulation of Keap1 contributes to poor prognosis and Axitinib resistance of renal cell carcinoma via upregulation of Nrf2 expression.

Kelch­like ECH­associated protein 1 (Keap1)/nuclear factor erythroid 2­related factor 2 (Nrf2) signaling has a protective effect on normal cells. A number of previous studies demonstrated that Keap1/Nrf2 signaling is associated with drug resistance in numerous tumors. The aim of the present study was to investigate the roles of Keap1 in renal cell carcinoma (RCC) and its effect on sensitivity to chemotherapy. Reverse transcription­quantitative polymerase chain reaction was used to detect the mRNA expression of Keap1 in 45 cases of RCC tumors and adjacent normal tissues. A total of five randomly selected patients with RCC, five RCC cell lines and normal renal tubular cells were examined to detect the protein and mRNA expressions of Keap1. The 5­year survival rate was analyzed by Kaplan­Meier analysis. The cell viability was assessed by a Cell Counting kit­8 assay. The cell apoptosis and reactive oxygen species (ROS) were determined by flow cytometry. The expressions of associated proteins were determined by western blot analysis. It was identified that in RCC tissues and RCC cell lines, the expression of Keap1 was downregulated, which was considered to be associated with poor prognosis. In total, 1 µM Axitinib significantly decreased cell viability, promoted ROS release and induced cell apoptosis in ACHN cells. Silencing Keap1 was able to reverse the inhibitory effect of Axitinib and enhance the protein expressions of Nrf2, NAD(P)H dehydrogenase [quinone] 1 and heme oxygenase 1. However, silencing Nrf2 increased the cell sensitivity to Axitinib. Under Axitinib condition, overexpressing Nrf2 was able to increase cell viability; however, overexpressing Keap1 resulted in an opposite effect. Keap1 serves as a tumor suppressor; its low expression was associated with poor prognosis and a decreased sensitivity of RCC cells to Axitinib. A possible mechanism underlying Axitinib resistance may involve Nrf2 overexpression.

Clinicopathological characteristics of renal solitary fibrous tumor: A single institution experience.

To analyze the clinical characteristics, treatment modalities and outcomes of adult renal solitary fibrous tumors (SFT) treated at a single institution. Demographic, diagnostic, surgical, and pathological findings of patients who had undergone radical nephrectomy (RN) due to renal SFT were collected from the database of a single institution and were retrospectively reviewed. Ten patients (6 men and 4 women) were diagnosed with renal SFT in our institution between January 1, 2000 and December 31, 2016. The mean age was 50.9 ±â€Š8.2 years (range, 38-63 years). Of the 10 patients, 6 were asymptomatic, 2 presented with flank pain, 1 presented with abdominal discomfort, and 1 presented with haematuria. Computed tomography scans were obtained for all patients. Open RN was performed on 6 patients, and laparoscopic RN was performed on 4 patients. The mean tumor size was 10.23 ±â€Š4 cm (range, 5.3-19 cm). Pathological diagnosis revealed that the tumors in 8 patients were benign, while those in the other 2 patients were malignant renal SFT. No recurrence occurred during a mean follow-up period of 47.3 ±â€Š21.5 months (range, 16-85 months). Renal SFT is extremely rare, and its diagnosis may be challenging because of a lack of typical imaging manifestations. RN is a safe treatment modality for benign or low-grade malignant renal SFT, ensuring favorable outcomes.

Association Between the Asp312Asn, Lys751Gln, and Arg156Arg Polymorphisms in XPD and the Risk of Prostate Cancer.

Prostate cancer is the most common solid cancer and genetic factors play important roles in its pathogenesis. XPD is one of the 8 core genes involved in the nucleotide excision repair pathway. The relationship between Asp312Asn, Lys751Gln, and Arg156Arg polymorphisms in XPD and prostate cancer risk is a controversial topic. Therefore, we conducted a meta-analysis to explore the relationship between these 3 polymorphisms and the risk of developing prostate cancer. We searched the electronic literature in PubMed and Google Scholar for all relevant studies (last updated January 1, 2017). The pooled odds ratios and 95% confidence intervals for the associations between the Asp312Asn, Lys751Gln, or Arg156Arg polymorphisms in XPD and prostate cancer risk were calculated. To evaluate the effects of specific study characteristics on the association of these 3 polymorphisms and prostate cancer risk, we performed subgroup analysis if 2 or more studies were available. After an extensive literature review, 7 publications regarding Asp312Asn genotype distribution with 8 case-controls, 9 publications regarding Lys751Gln genotype distribution with 10 case-controls, and 3 publications regarding Arg156Arg genotype distribution with 4 case-controls were selected. The results showed that Asp312Asn (odds ratio = 1.34, 95% confidence interval: 0.96-1.87, P = .000), Lys751Gln (odds ratio = 0.98, 95% confidence interval: 0.89-1.08, P = .986), and Arg156Arg (odds ratio = 1.05, 95% confidence interval: 0.91-1.22, P = .57) polymorphisms do not increase the risk of prostate cancer in the dominant model. Further, in the subgroup analysis by ethnicity, no relationships were observed between Lys751Gln and Arg156Arg polymorphisms and prostate cancer risk. However, stratified analysis by ethnicity revealed that Asp312Asn affects African (odds ratio = 1.57, 95% confidence interval: 1.06-2.33, P = .382) and Asian populations (odds ratio = 2.09, 95% confidence interval: 1.39-3.14, P = .396) in homozygote comparison. In conclusion, this meta-analysis suggests that there is no general association between the Asp312Asn, Lys751Gln, and Arg156Arg polymorphisms in XPD and prostate cancer susceptibility.

Intravenous misplacement of the nephrostomy catheter following percutaneous nephrostolithotomy: two case reports and literature review.

BACKGROUND: Intravenous misplacement of a nephrostomy tube after percutaneous nephrostolithotomy (PCNL) is very rare in clinical experiences. This report summarizes the characteristics and management of intravenous misplacement. CASE PRESENTATION: We present two uncommon cases of intravenous nephrostomy catheter misplacement after PCNL from among 4220 patients who underwent PCNL between January 2009 and December 2015. The tip of the tube was located in the inferior vena cava in one case and in the renal vein in the other. We preferably performed open surgery to treat the two patients, mainly to remove the residual calculi and to prepare for any possible adverse event. All patients were successfully managed and discharged uneventfully. CONCLUSION: Intravenous nephrostomy tube misplacement is an uncommon PCNL complication. Furthermore, the study illustrates the importance of prompt diagnosis of renal vein perforation and its prompt management using open surgery, similar to conservative therapies.

Small interference RNA targeting Krüppel-like factor 8 inhibits the renal carcinoma 786-0 cells growth in vitro and in vivo.

PURPOSE: Krüppel-like factor 8 (KLF8) plays an important role in oncogenic transformation and is highly overexpressed in several types of human cancer. We investigated the expression of KLF8 in renal cell carcinoma (RCC) tissues and the role of small interference RNA targeting KLF8 on growth, cell cycle, and apoptosis of human renal carcinoma cell line 786-0 in vitro and in vivo. METHODS: The expression of KLF8 protein and mRNA in human renal carcinoma samples was detected by immunochemistry and reverse transcription polymerase chain reaction (RT-PCR). The effects of small interference RNA (siRNA) targeting KLF8 on growth, invasiveness, cell cycle, and apoptosis of 786-0 cells were evaluated by MTT assay, Matrigel Invasion Assay, and flow cytometry in vitro. We also investigated effect of siRNA targeting KLF8 on growth of 786-0 cells in nude mice in vivo. RESULTS: Immunohistochemistry and RT-PCR results showed the expression of KLF8 protein and mRNA in RCC specimens was significantly higher than that in the adjacent non-tumorous renal tissues (P < 0.001). KLF8-siRNA depressed the cellular growth and invasion of 786-0 cells in vitro. The flow cytometry results revealed that KLF8-siRNA could induce an increase in G0/G1 phase cells and induce cell apoptosis. Intratumor injection of siRNA targeting KLF8 inhibited the growth of 786-0 cells in vivo in nude mice tumor model. CONCLUSIONS: KLF8 possibly involved in regulating the cell growth, invasion, apoptosis, and proliferation of renal carcinoma cancer cells. Blocking the KLF8 channel might be a potential therapeutic strategy for RCC.

Upregulation of GRP78 in renal cell carcinoma and its significance.

OBJECTIVES: To investigate the expression of GRP78 in human renal cell carcinoma (RCC) and its significance. METHODS: We studied RNA and tissue section of a tumor and adjacent nontumorous renal tissues obtained from radical nephrectomy specimens of 42 patients and RCC cell lines. We used reverse transcriptase-PCR and immunohistochemistry to detect the GRP78 mRNA and protein expression, respectively. RESULTS: Reverse transcriptase-PCR revealed that GRP78 mRNA is positively expressed in RCC cell lines (786-0, OS-RC-2, and Caki-1); the GRP78 mRNA expression in the RCC and adjacent nontumorous renal tissues was 0.88 +/- 0.34 and 0.44 +/- 0.15, respectively (P < .001). The GRP78 protein was found in RCC cell lines. Immunohistochemistry results also showed that the level of GRP78 protein expression of RCC tissues was significantly higher than that of the adjacent nontumorous renal tissues (P < .001). The high levels of GRP78 mRNA and protein expression were related to the large tumor size and high clinical stage (P < .001) but not to sex, age, and cell differentiate (P > .05). CONCLUSIONS: To our knowledge, the present study is the first to report the upregulated expression of GRP78 and that it is possibly involved in pathogenesis of RCC.