Lycopene from tomatoes and tomato products exerts renoprotective effects by ameliorating oxidative stress, apoptosis, pyroptosis, fibrosis, and inflammatory injury in calcium oxalate nephrolithiasis: the underlying mechanisms.

Several mechanisms underlying nephrolithiasis, one of the most common urological diseases, involve calcium oxalate formation, including oxidative stress, inflammatory reactions, fibrosis, pyroptosis, and apoptosis. Although lycopene has strong antioxidant activity, its protective effects against CaOx-induced injury have not yet been reported. This study aimed to systematically investigate the protective effects of lycopene and explore its mechanisms and molecular targets. Crystal deposition, renal function, oxidative stress, inflammatory response, fibrosis, pyroptosis, and apoptosis were assessed to evaluate the renoprotective effects of lycopene against crystal formation in a CaOx rat model and oxalate-stimulated NRK-52E and HK-2 cells. Lycopene markedly ameliorated crystal deposition, restored renal function, and suppressed kidney injury by reducing oxidative stress, apoptosis, inflammation, fibrosis, and pyroptosis in the rats. In cell models, lycopene pretreatment reversed reactive oxygen species increase, apoptotic damage, intracellular lactate dehydrogenase release, cytotoxicity, pyroptosis, and extracellular matrix deposition. Network pharmacology and proteomic analyses were performed to identify lycopene target proteins under CaOx-exposed conditions, and the results showed that Trappc4 might be a pivotal target gene for lycopene, as identified by cellular thermal shift assay and surface plasmon resonance analyses. Based on molecular docking, molecular dynamics simulations, alanine scanning mutagenesis, and saturation mutagenesis, we observed that lycopene directly interacts with Trappc4 via hydrophobic bonds, which may be attributed to the PHE4 and PHE142 residues, preventing ERK1/2 or elevating AMPK signaling pathway phosphorylation events. In conclusion, lycopene might ameliorate oxalate-induced renal tubular epithelial cell injury via the Trappc4/ERK1/2/AMPK pathway, indicating its potential for the treatment of nephrolithiasis.

Serum ribonucleotide reductase M2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B patients.

It is known that ribonucleotide reductase M2 (RRM2) could be induced by hepatitis B virus (HBV) via DNA damage response. However, whether RRM2 is a potential biomarker for diagnosing and monitoring liver fibrosis in chronic hepatitis B (CHB) patients is still unclear. In this study, CHB patients from GSE84044 (a transcriptome data from GEO data set) were downloaded and RRM2 was selected as a hub gene. Interestingly, a positive correlation was found between serum RRM2 and liver fibrosis stage. The similar results were found in CHB patients with normal alanine aminotransferase (ALT). Notably, RRM2 could effectively differentiate preliminary fibrosis from advanced fibrosis in CHB patients with/without normal ALT. In addition, RRM2 had a better performance in diagnosing liver fibrosis than two commonly used noninvasive methods (aspartate aminotransferase-to-platelet ratio index and fibrosis index based on the four factors), two classic fibrotic biomarkers (hyaluronic acid and type IV collagen) as well as Mac-2 binding protein glycosylation isomer, a known serum fibrosis marker. Moreover, CHB patients with high RRM2, who were associated with advanced fibrosis, had higher expressions of immune checkpoints. Overall, serum RRM2 may be a promising biomarker for diagnosing and monitoring liver fibrosis in CHB patients.

Glucose dysregulation promotes oncogenesis in human bladder cancer by regulating autophagy and YAP1/TAZ expression.

Glucose dysregulation is strongly correlated with cancer development, and cancer is prevalent in patients with Type 2 diabetes (T2D). We aimed to elucidate the mechanism underlying autophagy in response to glucose dysregulation in human bladder cancer (BC). 220 BC patients were included in this retrospective study. The expression of YAP1, TAZ and AMPK, EMT-associated markers, and autophagy marker proteins was analysed by immunohistochemistry, western blotting, and quantitative real-time PCR (qPCR). Further, T24 and UMUC-3 BC cells were cultured in media with different glucose concentrations, and the expression of YAP1, TAZ, AMPK and EMT-associated markers, and autophagy marker proteins was analysed by western blotting and qPCR. Autophagy was observed by immunofluorescence and electron microscopy. BC cell viability was tested using MTT assays. A xenograft nude mouse model of diabetes was used to evaluate tumour growth, metastasis and survival. A poorer pathologic grade and tumour-node-metastasis stage were observed in patients with BC with comorbid T2D than in others with BC. YAP1 and TAZ were upregulated in BC samples from patients with T2D. Mechanistically, high glucose (HG) promoted BC progression both in vitro and in vivo and inhibited autophagy. Specifically, various autophagy marker proteins and AMPK were negatively regulated under HG conditions and correlated with YAP1 and TAZ expression. These results demonstrate that HG inhibits autophagy and promotes cancer development in BC. YAP1/TAZ/AMPK signalling plays a crucial role in regulating glucose dysregulation during autophagy. Targeting these effectors exhibits therapeutic significance and can serve as prognostic markers in BC patients with T2D.

GAS5-inhibited hepatocyte pyroptosis contributes to hepatic stellate cell inactivation via microRNA-684 and AHR.

Hepatocyte pyroptosis has been shown to be involved in liver damage progression. Previously, we found that growth arrest-specific 5 (GAS5) is a regulator of hepatic stellate cell (HSC) activation. However, whether GAS5 plays a role in hepatocyte pyroptosis remains unclear. In this study, reduced GAS5 was shown in CCl4-treated mice and restoration of GAS5-inhibited liver fibrosis in vivo. Hepatocyte pyroptosis participated in the effects of GAS5-inhibited liver fibrosis, associated with reduced caspase-1, NLRP3, and IL-1ß (hepatocyte pyroptosis markers). Notably, AHR expression, a suppressor of NLRP3, was enhanced by GAS5. Silencing AHR inhibited GAS5-mediated hepatocyte pyroptosis. GAS5 and AHR were targets of microRNA-684 (miR-684). In addition, the effects of GAS5 on hepatocyte pyroptosis could be inhibited by miR-684. Interestingly, GAS5-mediated hepatocyte pyroptosis contributed to HSC inactivation. In conclusion, we demonstrate that GAS5 inhibits hepatocyte pyroptosis and HSC activation, at least in part, via regulation of miR-684 and AHR.

Ginsenoside Rh2 promotes hepatic stellate cell ferroptosis and inactivation via regulation of IRF1-inhibited SLC7A11.

BACKGROUND: Sustained liver fibrosis may lead to cirrhosis. Activated hepatic stellate cells (HSCs) are crucial for liver fibrosis development. Ferroptosis, a newly iron-dependent regulated cell death, has been demonstrated to be involved in HSC inactivation. PURPOSE: Ginsenoside Rh2 (GRh2), a natural bioactive product derived from ginseng, has been shown to promote HSC inactivation. However, the effect of GRh2 on HSC ferroptosis remains unclear. METHODS: We explored the effects of GRh2 on liver fibrosis in vivo and in vitro. RNA-sequence analysis was performed in HSCs after GRh2 treatment. The crosstalk between ferroptotic HSCs and macrophages was also explored. RESULTS: GRh2 alleviated liver fibrosis in vivo. In vitro, GRh2 reduced HSC proliferation and activation via ferroptosis, with increased intracellular iron, reactive oxygen species, malondialdehyde and glutathione depletion. The expression of SLC7A11, a negative regulator of ferroptosis, was obviously reduced by GRh2. Interestingly, interferon regulatory factor 1 (IRF1), a transcription factor, was predicted to bind the promoter region of SCL7A11. The interaction between IRF1 and SCL7A11 was further confirmed by the results of chromatin immunoprecipitation and luciferase reporter assays. Furthermore, loss of IRF1 led to an increase in SCL7A11, which contributed to the suppression of HSC ferroptosis and the enhancement of HSC activation in GRh2-treated HSCs. Further studies revealed that GRh2-induced HSC ferroptosis contributed to the inhibition of macrophage recruitment via regulation of inflammation-related genes. Moreover, GRh2 caused a reduction in liver inflammation in vivo. CONCLUSION: Collectively, GRh2 up-regulates IRF1 expression, resulting in the suppression of SLC7A11, which contributes to HSC ferroptosis and inactivation. GRh2 ameliorates liver fibrosis through enhancing HSC ferroptosis and inhibiting liver inflammation. GRh2 may be a promising drug for treating liver fibrosis.

Better prediction of clinical outcome in clear cell renal cell carcinoma based on a 6 metabolism-related gene signature.

It has been reported that metabolic disorders participate in the formation and progression of clear cell renal cell carcinoma (ccRCC). However, the predictive value of metabolism-related genes (MRGs) in clinical outcome of ccRCC is still largely unknown. Herein, a novel metabolism-related signature was generated to assess the effect of MRGs on the prognosis of ccRCC patients. Important module MRGs were selected by differentially expressed analysis and WGCNA. Subsequently, the hub MRGs were screened via univariate cox regression as well as LASSO regression. A new metabolism-related signature of 6 hub MRGs (PAFAH2, ACADSB, ACADM, HADH, PYCR1 and ITPKA) was constructed, with a good prognostic prediction ability in the TCGA cohort. The prediction accuracy of this signature was further confirmed in both GSE22541 and FAHWMU cohort. Interestingly, this MRG risk signature was highly correlated with tumor mutation burden and immune infiltration in ccRCC. Notably, lower PAFAH2, a member of 6 MRGs, was found in ccRCC. Knockdown of PAFAH2 contributed to renal cancer cell proliferation and migration. Collectively, a 6-MRG prognostic risk signature is generated to estimate the prognostic status of ccRCC patients, providing a novel insight in the prognosis prediction and treatment of ccRCC.

Genomic profiles of renal cell carcinoma in a small Chinese cohort.

Objectives: Our aim was to describe the molecular characteristics of Renal Cell Carcinoma (RCC) and develop a small panel of RCC-associated genes from a large panel of cancer-related genes. Materials and methods: Clinical data of 55 patients with RCC diagnosed in four hospitals from September 2021 to August 2022 were collected. Among the 55 patients, 38 were diagnosed with clear cell RCC (ccRCC), and the other 17 were diagnosed with non-clear cell RCC (nccRCC), including 10 cases of papillary renal cell carcinoma, 2 cases of hereditary leiomyomatosis and RCC syndrome (HLRCC), 1 eosinophilic papillary RCC, 1 tubular cystic carcinoma, 1 TFE3 gene fusion RCC, and 2 RCC with sarcomatoid differentiation. For each patient, 1123 cancer-related genes and 79 RCC-associated genes were analyzed. Results: The most frequent mutations in a large panel of 1123 cancer-related genes in the overall population of RCC patients were VHL (51%), PBRM1 (35%), BAP1 (16%), KMT2D (15%), PTPRD (15%), and SETD2 (15%). For ccRCC patients, mutations in VHL, PBRM1, BAP1, and SERD2 can reach 74%, 50%, 24%, and 18%, respectively, while for nccRCC patients, the most frequent mutation was FH (29%), MLH3 (24%), ARID1A (18%), KMT2D (18%), and CREBBP (18%). The germline mutation rate in all 55 patients reached 12.7% (five with FH, one with ATM, and one with RAD50). The small panel containing only 79 RCC-associated genes demonstrated that mutations of VHL, PBRM1, BAP1, and SETD2 in ccRCC patients were 74%, 50%, 24%, and 18% respectively, while for the nccRCC cohort, the most frequent mutations were FH (29%), ARID1A (18%), ATM (12%), MSH6 (12%), BRAF (12%), and KRAS (12%). For ccRCC patients, the spectrum of mutations by large and small panels was almost the same, while for nccRCC patients, the mutation spectrum showed some differences. Even though the most frequent mutations (FH and ARID1A) in nccRCC were both demonstrated by large panels and small panels, other less frequent mutations such as MLH3, KMT2D, and CREBBP were not shown by the small panel. Conclusion: Our study revealed that nccRCC is more heterogeneous than ccRCC. For nccRCC patients, the small panel shows a more clear profile of genetic characteristics by replacing MLH3, KMT2D, and CREBBP with ATM, MSH6, BRAF, and KRAS, which may help predict prognosis and make clinical decisions.

Prognostic value of genomic mutations in metastatic prostate cancer.

Metastatic prostate cancer (mPC) has a poor prognosis, and new treatment strategies are currently being offered for patients in clinical practice, but mPC is still incurable. A considerable proportion of patients with mPC harbor homologous recombination repair (HRR) mutations, which may be more sensitive to poly (ADP-ribose) polymerase inhibitors (PARPis). We retrospectively included genomic and clinical data from 147 patients with mPC from a single clinical center, with a total of 102 circulating tumor DNA (ctDNA) samples and 60 tissue samples. The frequency of genomic mutations was analyzed and compared with that in Western cohorts. Cox analysis was used to assess progression-free survival (PFS) and prognostic factors related to prostate-specific antigen (PSA) after standard systemic therapy for mPC. The most frequently mutated gene in the HRR pathway was CDK12 (18.3%), followed by ATM (13.7%) and BRCA2 (13.0%). The remaining common ones were TP53 (31.3%), PTEN (12.2%), and PIK3CA (11.5%). The frequency of BRCA2 mutation was close to that of the SU2C-PCF cohort (13.3%), but the frequency of CDK12, ATM, and PIK3CA mutations was significantly higher than that in the SU2C-PCF cohort: 4.7%, 7.3%, and 5.3%, respectively. CDK12 mutation were less responsive to androgen receptor signaling inhibitors (ARSIs), docetaxel, and PARPi. BRCA2 mutation helps predict PARPi efficacy. Additionally, androgen receptor (AR)-amplified patients do not respond well to ARSIs, and PTEN mutation are associated with poorer docetaxel response. These findings support the genetic profiling of patients with mPC after diagnosis to guide treatment stratification to customize personalized treatment.

Risk Evaluation of Bone Metastases and a Simple Tool for Detecting Bone Metastases in Prostate Cancer: A Population-Based Study.

Introduction: Population-based estimates of the incidence and prognosis of bone metastases in prostate cancer (PC) are lacking. We aimed to characterize the incidence and risk of bone metastases and develop a simple tool for the prediction of bone metastases among patients with PC. Methods: Data were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. A total of 75698 patients with PC with confirmed presence or absence of bone metastases at diagnosis between 1975 and 2019 in the United States were used for analysis. Data were stratified by age, race, residence, median income, prostate-specific antigen (PSA) values, tumor size, distant metastatic history, and positive lymph node scores. Multivariable logistic and Cox regressions were performed to identify predictors of bone metastases and factors correlated with all-cause mortality. Classification tree analysis was performed to establish a model. Results: After patients with PC with missing data were excluded, 75698 cases remained. Among these, 3835 patients had bone metastases. Incidence proportions were highest in patients with a high prostate-specific antigen (PSA) value (odds ratio (OR), 2.49; 95% confidence interval (CI), 1.35-4.35; p < 0.002). Multivariable Cox regression and risk analyses indicated that high PSA values (hazards ratio (HR), 19.8; 95% CI, 18.5-21.2; p < 0.001) and high positive lymph node scores (vs. score 0; HR, 8.65; 95% CI, 7.89-9.49; p < 0.001) were significant risk factors for mortality. Meanwhile, in the predication tree analysis, PSA values and lymph node scores were the most significant determining factors in two models. Median survival among the patients with PC was 78 months, but only 31 months among those with bone metastases. Conclusion: Patients with PC with high PSA values or high positive lymph node scores were at a significantly higher risk of bone metastases. Our study may provide a simple and accurate tool to identify patients with PC at high risk of bone metastases based on population-based estimates.

Sophocarpine inhibits tumor progression by antagonizing the PI3K/AKT/mTOR signaling pathway in castration-resistant prostate cancer.

Objective: The objective of this study was to investigate the inhibitory effect of sophocarpine on the progression of castration-resistant prostate cancer (CRPC) and the underlying molecular mechanism. Methods: DU145 and PC3 cells (two CRPC cell lines), incubated with different concentrations of sophocarpine, were used. Cell Counting Kit-8 assay, real-time cellular analysis, and colony formation assay were conducted to evaluate the proliferation of CRPC cells. Cytometry flow analysis was performed to evaluate the apoptosis rate of CRPC cells. Wound healing and Transwell invasion assays were performed and the levels of the epithelial-mesenchymal transition (EMT)-related proteins were determined to analyze cell migration and invasion abilities. A xenografted tumor model of nude mice was used to examine the anti-cancer effect of sophocarpine on CRPC. Western blotting was performed to evaluate the activities of the PI3K/AKT/mTOR signaling pathway both in cells and tumor tissues. Results: In vitro tests showed that sophocarpine suppressed the proliferation of CRPC cells, reduced the migration and invasion abilities, and increased the apoptosis rate. In vivo, sophocarpine decreased the weight and volume of tumor tissues. Mechanically, sophocarpine exerted its anti-cancer effects by inactivating PI3K/AKT/mTOR signaling. Conclusion: Sophocarpine inhibited the progression of CRPC by downregulating the PI3K/AKT/mTOR signaling pathway and showed a potential to be an anti-cancer agent against CRPC.

Development and validation of a novel necroptosis-related score to improve the outcomes of clear cell renal cell carcinoma.

Necroptosis has been indicated as a key regulator of tumor progression. However, the prognostic regulatory role of necroptosis in clear cell renal cell carcinoma (ccRCC) needs to be further investigated. In this study, necroptosis-related subtypes were identified by mining the public cohort (n = 530) obtained from The Cancer Genome Atlas. By applying Principal Component Analysis (PCA), the necroptosis-related scores (N-Score) were developed to assess the prognosis procession of ccRCC. The results were further validated by an external clinical cohort (n = 116) obtained from the First Affiliated Hospital of Wenzhou Medical University. It has been found that N-Score could precisely distinguish the prognostic outcomes of patients as an independent risk factor (Hazard ratio = 4.990, 95% confidence interval (CI) = 2.007-12.403, p < 0.001). In addition, changes in N-Score were associated with differences in tumor mutational burden as well as immune infiltration characterization. Moreover, higher N-Scores were also correlated significantly molecular drug sensitivity and stronger immune checkpoint activity. Notably, the prognosis of ccRCC could be effectively guided by combining the N-Scores and external clinical indicators. In conclusion, N-Scores could be served as a robust and effective biomarker to improve the prognosis outcomes and targeted therapy of ccRCC.

Analysis of BRCA Germline Mutations in Chinese Prostate Cancer Patients.

Recent studies have indicated that prostate cancer (PCa) with BRCA2 mutations is more aggressive. However, these reports mostly focused on Caucasus populations, and large-scale studies on BRCA mutations in Chinese PCa populations remain limited. Herein, we screened, from multiple centers in China, a total of 172 patients with PCa carrying BRCA1/2 germline mutations. The variant distribution and type, associated somatic variant, and frequency of the BRCA germline variants in these patients were analyzed retrospectively. We found that Chinese patients with PCa carrying BRCA1/2 germline mutations were diagnosed at an earlier age, i.e., 67 years (range, 34-89 years), and most had metastatic castration-resistant PCa (mCRPC) (54.65%, 94/172). The top three BRCA variants were frameshift, missense, and splicing variants. The overall pathogenic rates of the BRCA1 and BRCA2 variants were 17.46% (11/63) and 56.55% (82/145), respectively. Among the somatic mutations associated with BRCA2 germline mutations, the highest frequency was for FOXA1 (circulating tumor DNA [ctDNA] sequencing, 7.4%; tissue samples, 52%) and NCOR2 mutations (ctDNA sequencing, 7.4%; tissue samples, 24%); TP53 was the dominant somatic mutation associated with BRCA1 germline mutations (ctDNA sequencing, 25%; tissue samples, 17%). Ultimately, in Chinese patients, PCa with BRCA1/2 germline mutations tends to be more aggressive. Compared with BRCA1, BRCA2 has a higher frequency of germline pathogenic mutations. FOXA1, NCOR2, and TP53 somatic mutations associated with higher BRCA1/2 germline pathogenic mutations. Our description of BRCA germline mutations in the Chinese PCa patients provides more reference data for the precise diagnosis and treatment of Chinese PCa patients.

A HALP score-based prediction model for survival of patients with the upper tract urothelial carcinoma undergoing radical nephroureterectomy.

The combination of hemoglobin, albumin, lymphocyte, and platelet (HALP) score has been confirmed as an important risk biomarker in several cancers. Hence, we aimed at evaluating the prognostic value of the HALP score in patients with non-metastatic upper tract urothelial carcinoma (UTUC). We retrospectively enrolled 533 of the 640 patients from two centers (315 and 325 patients, respectively) who underwent radical nephroureterectomy (RNU) for UTUC in this study. The cutoff value of HALP was determined using the Youden index by performing receiver operating characteristic (ROC) curve analysis. The relationship between postoperative survival outcomes and preoperative HALP level was assessed using Kaplan-Meier analysis and Cox regression analysis. As a result, the cutoff value of HALP was 28.67 and patients were then divided into HALP<28.67 group and HALP≥28.67 group. Kaplan-Meier analysis and log-rank test revealed that HALP was significantly associated with overall survival (OS) (P<0.001) and progression-free survival (PFS) (P<0.001). Multivariate analysis demonstrated that lower HALP score was an independent risk factor for OS (HR=1.54, 95%CI, 1.14-2.01, P=0.006) and PFS (HR=1.44, 95%CI, 1.07-1.93, P=0.020). Nomograms of OS and PFS incorporated with HALP score were more accurate in predicting prognosis than without. In the subgroup analysis, the HALP score could also stratify patients with respect to survival under different pathologic T stages. Therefore, pretreatment HALP score was an independent prognostic factor of OS and PFS in UTUC patients undergoing RNU.

A Newly Defined Pyroptosis-Related Gene Signature for the Prognosis of Bladder Cancer.

BACKGROUND: Bladder cancer (BC), as the most common urinary system tumor type and the main cause of tumor-related death, has an unsatisfactory prognosis. In recent years, related literature has proposed that cell pyroptosis is an inflammatory form of programmed cell death. However, in BC, the relationship between the expression of pyroptosis-related genes and the prognosis has not been elucidated. METHODS: We got the RNA sequencing data from TCGA and GEO datasets. Fifty-two pyroptosis-related genes were extracted for further explore. Then, we compared the gene expression levels between the normal bladder and BC tissues. After that, we develop and validate a pyroptosis-related gene prognostic model and made following functional enrichment analysis and single-sample gene set enrichment analysis of the differentially expressed genes between the high- and low-risk groups. RESULTS: Twenty-nine differentially expressed genes (DEGs) were found between normal and tumor tissues. Based on the median score calculated by the risk score formula from 8 pyroptosis-related genes, 414 patients were equally divided into low- and high-risk subgroups. The survival probability of BC patients in the high-risk group was significantly lower than that in the low-risk group (P < 0.001). Through multivariate analysis, our risk score is an independent factor predicting OS in BC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis show that high-risk populations are rich in immune-related genes and have a decreased immune status. All the above results have been externally verified from GEO cohort. CONCLUSION: Pyroptosis-related genes are closely related to tumor immunity and are a potential prognostic tool for predicting BCs.

Association of preoperative systemic Immune-inflammation Index and Prognostic Nutritional Index with survival in patients with Upper Tract Urothelial Carcinoma.

Background: Both systemic inflammation response and malnutrition are closely related to poor prognosis in patients with certain types of solid tumor. This study investigated the prognostic value of the preoperative combination of systemic immune-inflammation index and prognostic nutritional index (SII-PNI) in patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Methods: The predictive ability of SII-PNI was developed and further validated in a cohort of 525 UTUC patients (253 in the training cohort and 272 in the validation cohort) who received RNU. Results: Survival analysis indicated that a SII ≥672.44 was significantly associated with worse overall survival (OS), cancer-specific survival (CSS), and recurrence-free survival (RFS) while a PNI ≥47.83 was associated with better survival outcomes (All P-values < 0.05). The combination of simultaneously SII ≥672.44 and PNI <47.83 was a powerful independent risk factor for OS, CSS, and RFS (P < 0.05). The SII-PNI had the largest area under the curve (AUC) compared to that for SII or PNI alone and other clinical factors, indicating its superior for predicting survival. In addition, the incorporation of the SII-PNI into established nomograms or current clinical parameters such as pathologic T stage and N stage, achieved higher c-indexes or larger AUC than without, indicating that adding SII-PNI helped predict prognosis. All results were found in the training cohort and confirmed in the validation cohort. Conclusions: SII-PNI was a strong independent predictor of UTUC patients after RNU.

Circular RNA circRNA_103809 Accelerates Bladder Cancer Progression and Enhances Chemo-Resistance by Activation of miR-516a-5p/FBXL18 Axis.

BACKGROUND: Numerous researches have suggested that circular RNAs (circRNAs) play critical functions in bladder cancer (BC) progression. This study aims to investigate the potential roles of circRNA_103809 in regulating BC development. METHODS: qRT-PCR was used to analyze gene expression. CCK8 and colony formation were used to analyze cell proliferation. Transwell was utilized to examine cell migration and invasion. Gemcitabine was used to analyze the effect of circRNA_103809 on the chemo-resistance of BC cells. Luciferase reporter assay was performed to detect the RNA interactions. RESULTS: circRNA_103809 was highly expressed in BC tissues and cell lines. CircRNA_103809 high expression was associated with a poor progression in BC patients. CircRNA_103809 knockdown impaired the growth and metastasis of BC cells. Furthermore, circRNA_103809 silencing increased the sensitivity of BC cells to Gemcitabine treatment. CircRNA_103809 was the sponge for miR-516a-5p and promoted FBXL18 expression via restraining miR-516a-5p activity. CONCLUSION: circRNA_103809 promotes proliferation, migration, invasion and chemo-resistance of BC cells through regulating miR-516a-5p/FBXL18 axis.

LncRNA LINC00665 Promotes Prostate Cancer Progression via miR-1224-5p/SND1 Axis.

BACKGROUND: Increasing researches have revealed a critical role of long noncoding RNAs (lncRNAs) in tumor progression. LINC00665 is a poorly investigated lncRNA. In this research, we sought to determine the potential role of LINC00665 in prostate cancer (PC) progression. METHODS: LINC00665 expression was analyzed by bioinformatics method and qRT-PCR. Proliferation was determined via CCK8 and colony formation assays. Transwell assay was conducted to analyze migration and invasion. Xenograft assay was used to test the roles of LINC00665 in vivo. Luciferase reporter assay, pulldown assay and RIP assay were utilized to confirm the interaction between LINC00665 and miR-1224-5p. RESULTS: LINC00665 expression was increased in PC samples in contrast to control tissues, according to bioinformatics analysis and qRT-PCR validation. LINC00665 high expression was related to a poor prognosis. LINC00665 knockdown markedly attenuated growth and metastasis of PC cells and impaired tumor propagation in vivo. Mechanistic investigation revealed that LINC00665 was the sponge for miR-1224-5p. By inhibiting miR-1224-5p level, LINC00665 dramatically promoted the expression of SND1 in PC cells. Ectopic expression of SND1 significantly rescued the effects of LINC00665 silencing. CONCLUSION: LINC00665 is a novel oncogenic gene in PC by targeting miR-1224-5p/SND1 pathway and may be a therapeutic target.

Acute renal impairment characterization using diffusion magnetic resonance imaging: Validation by histology.

Diffusion magnetic resonance imaging has been demonstrated to be a simple, noninvasive and accurate method for the detection of renal microstructure and microcirculation, which are closely linked to renal function. Moreover, serum endothelin-1 (ET-1) was also reported as a good indicator of early renal injury. The aim of this study was to evaluate the feasibility and capability of diffusion MRI and ET-1 to detect acute kidney injury by an operation simulating high-pressure renal pelvic perfusion, which is commonly used during ureteroscopic lithotripsy. Histological findings were used as a reference. Fourteen New Zealand rabbits in an experimental group and 14 in a control group were used in this study. Diffusion tensor imaging and intravoxel incoherent motion diffusion-weighted imaging were acquired by a 3.0 T MRI scanner. Significant corticomedullary differences were found in the values of the apparent diffusion coefficient (ADC), pure tissue diffusion, volume fraction of pseudo-diffusion (fp) and fractional anisotropy (FA) (P < 0.05 for all) in both preoperation and postoperation experimental groups. Compared with the control group, the values of cortical fpmean , medullary ADCmean and FAmean decreased significantly (P < 0.05) after the operation in the experimental group. Also, the change rate of medullary ADCmean in the experimental group was more pronounced than that in the control group (P = 0.018). No significant change was found in serum ET-1 concentration after surgery in either the experimental (P = 0.80) or control (P = 0.17) groups. In the experimental group, histological changes were observed in the medulla, while no visible change was found in the cortex. This study demonstrated the feasibility of diffusion MRI to detect the changes of renal microstructure and microcirculation in acute kidney injury, with the potential to evaluate renal function. Moreover, the sensitivity of diffusion MRI to acute kidney injury appears to be superior to that of serum ET-1.

Quantum Limited Superresolution of an Incoherent Source Pair in Three Dimensions.

The error in estimating the separation of a pair of incoherent sources from radiation emitted by them and subsequently captured by an imager is fundamentally bounded below by the inverse of the corresponding quantum Fisher information (QFI) matrix. We calculate the QFI for estimating the full three-dimensional pair separation vector, extending previous work on pair separation in one and two dimensions. We also show that the pair-separation QFI is, in fact, identical to source localization QFI, which underscores the fundamental importance of photon-state localization in determining the ultimate estimation-theoretic bound for both problems. We also propose general coherent-projection bases that can attain the QFI in two special cases. We present simulations of an approximate experimental realization of such quantum limited pair superresolution using the Zernike basis, confirming the achievability of the QFI bounds.

Downregulation of circular RNA hsa_circ_0000144 inhibits bladder cancer progression via stimulating miR-217 and suppressing RUNX2 expression.

Although increasing aberrantly expressed circular RNAs (circRNAs) have been identified among many human cancer tissues, their roles in tumor progression still remain largely unknown. In bladder cancer, the function of hsa_circ_0000144 has not been reported. In our study, we found hsa_circ_0000144 as a novel oncogene in bladder cancer by bioinformatics analysis. We found that hsa_circ_0000144 expression was significantly upregulated in bladder cancer tissues compared with adjacent normal tissues, and its high expression was related with poor prognosis. Additionally, knockdown of hsa_circ_0000144 remarkably suppressed the proliferation and invasion of bladder cancer cells in vitro. Hsa_circ_0000144 silence also led to reduced tumor volumes in vivo. In mechanism, we found that hsa_circ_0000144 was a sponge of miR-217 while miR-217 targeted RUNX2. Our results indicated that the expression of miR-217 was inversely correlated with that of both hsa_circ_0000144 and RUNX2 in bladder cancer tissues. Rescue assays showed that either inhibition of miR-217 or restoration of RUNX2 reversed the suppressive effects of hsa_circ_0000144 knockdown on bladder cancer cell proliferation and invasion. Taken together, these findings demonstrated that hsa_circ_0000144 exerts oncogenic roles in bladder cancer via repressing miR-217 to facilitate RUNX2 expression.