Diagnostic performance of MRI in detecting prostate cancer in patients with prostate-specific antigen levels of 4-10 ng/mL: a systematic review and meta-analysis.

OBJECTIVE: To investigate the diagnostic performance of MRI in detecting clinically significant prostate cancer (csPCa) and prostate cancer (PCa) in patients with prostate-specific antigen (PSA) levels of 4-10 ng/mL. METHODS: A computerized search of PubMed, Embase, Cochrane Library, Medline, and Web of Science was conducted from inception until October 31, 2023. We included articles on the use of MRI to detect csPCa or PCa at 4-10 ng/mL PSA. The primary and secondary outcomes were MRI performance in csPCa and PCa detection, respectively; the estimates of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were pooled in a bivariate random-effects model. RESULTS: Among the 19 studies (3879 patients), there were 10 (2205 patients) and 13 studies (2965 patients) that reported MRI for detecting csPCa or PCa, respectively. The pooled sensitivity and specificity for csPCa detection were 0.84 (95% confidence interval [CI], 0.79-0.88) and 0.76 (95%CI, 0.65-0.84), respectively, for PCa detection were 0.82 (95%CI, 0.75-0.87) and 0.74 (95%CI, 0.65-0.82), respectively. The pooled NPV for csPCa detection was 0.91 (0.87-0.93). Biparametric magnetic resonance imaging also showed a significantly higher sensitivity and specificity relative to multiparametric magnetic resonance imaging (both p < 0.01). CONCLUSION: Prostate MRI enables the detection of csPCa and PCa with satisfactory performance in the PSA gray zone. The excellent NPV for csPCa detection indicates the possibility of biopsy decision-making in patients in the PSA gray zone, but substantial heterogeneity among the included studies should be taken into account. CLINICAL RELEVANCE STATEMENT: Prostate MRI can be considered a reliable and satisfactory tool for detecting csPCa and PCa in patients with PSA in the "gray zone", allowing for reducing unnecessary biopsy and optimizing the overall examination process. KEY POINTS: Prostate-specific antigen (PSA) is a common screening tool for prostate cancer but risks overdiagnosis. MRI demonstrated excellent negative predictive value for prostate cancer in the PSA gray zone. MRI can influence decision-making for these patients, and biparametric MRI should be further evaluated.

Network analysis of smoking-related sleep characteristics in Chinese adults.

The associations between multiple sleep characteristics and smoking behavior are inconsistent, and it is unclear which sleep characteristics are most crucial for tobacco prevention. This study aimed to explore the associations between smoking status/intensity and multiple sleep characteristics and to identify the potential core domain of smoking-related sleep using network analysis. Data were obtained from a survey of cancer-related risk factors among Chinese adults. Logistic regression models were used to quantify the associations between sleep characteristics and smoking status/intensity. Network analyses were employed to identify the core sleep characteristics. A total of 5,228 participants with a median age of 44 years old were included in the study. Current smoking was significantly positively associated with long nap time, difficulty falling asleep, late bedtime, getting up after 7 am, and waking up earlier than expected. There was significant positive association between current smoking and short sleep duration in young adults under 45 years old. Late bedtime and getting up after 7 am were only associated with current heavy smoking, but not current light smoking. Network analyses showed that multiple smoking-related sleep characteristics were interconnected, with difficulty falling asleep and late bedtime as central characteristics in the network. The study found that the associations between sleep characteristics and smoking varied by age and smoking intensity and highlights the potential benefits of sleep health promotion in smoking cessation, with a particular focus on difficulty falling asleep and late bedtime.

Effect of preoperative PI-RADS assessment on pathological outcomes in patients who underwent radical prostatectomy.

OBJECTIVE: To assess the effect of preoperative MRI with standardized Prostate Imaging-Reporting and Data System (PI-RADS) assessment on pathological outcomes in prostate cancer (PCa) patients who underwent radical prostatectomy (RP). PATIENTS AND METHODS: This retrospective cohort study included patients who had undergone prostate MRI and subsequent RP for PCa between January 2017 and December 2022. The patients were divided into the PI-RADS group and the non-PI-RADS group according to evaluation scheme of presurgery MRI. The preoperative characteristics and postoperative outcomes were retrieved and analyzed. The pathological outcomes included pathological T stage (pT2 vs. pT3-4) and positive surgical margins (PSMs). Patients were further stratified according to statistically significant preoperative variables to assess the difference in pathological outcomes. A propensity score matching based on the above preoperative characteristics was additionally performed. RESULTS: A total of 380 patients were included in this study, with 201 patients in the PI-RADS group and 179 in the non-PI-RADS group. The two groups had similar preoperative characteristics, except for clinical T stage (cT). As for pathological outcomes, the PI-RADS group showed a significantly lower percentage of pT3-4 (21.4% vs. 48.0%, p < 0.001), a lower percentage of PSMs (31.3% vs. 40.9%, p = 0.055), and a higher concordance between the cT and pT (79.1% vs. 64.8%, p = 0.003). The PI-RADS group also showed a lower proportion of pT3-4 (p < 0.001) in the cT1-2 subgroup and the cohort after propensity score matching. The PSM rate of cT3 patients was reduced by 39.2% in the PI-RADS group but without statistical significance (p = 0.089). CONCLUSIONS: Preoperative MRI with standardized PI-RADS assessment could benefit the decision-making of patients by reducing the rate of pathologically confirmed non-organ-confined PCa after RP and slightly reducing the PSM rate compared with non-PI-RADS assessment.

An MRI-based grading system for preoperative risk estimation of positive surgical margin after radical prostatectomy.

OBJECTIVE: To construct a simplified grading system based on MRI features to predict positive surgical margin (PSM) after radical prostatectomy (RP). METHODS: Patients who had undergone prostate MRI followed by RP between January 2017 and January 2021 were retrospectively enrolled as the derivation group, and those between February 2021 and November 2022 were enrolled as the validation group. One radiologist evaluated tumor-related MRI features, including the capsule contact length (CCL) of lesions, frank extraprostatic extension (EPE), apex abutting, etc. Binary logistic regression and decision tree analysis were used to select risk features for PSM. The area under the curve (AUC), sensitivity, and specificity of different systems were calculated. The interreader agreement of the scoring systems was evaluated using the kappa statistic. RESULTS: There were 29.8% (42/141) and 36.4% (32/88) of patients who had PSM in the derivation and validation cohorts, respectively. The first grading system was proposed (mrPSM1) using two imaging features, namely, CCL ≥ 20 mm and apex abutting, and then updated by adding frank EPE (mrPSM2). In the derivation group, the AUC was 0.705 for mrPSM1 and 0.713 for mrPSM2. In the validation group, our grading systems showed comparable AUC with Park et al.'s model (0.672-0.686 vs. 0.646, p > 0.05) and significantly higher specificity (0.732-0.750 vs. 0.411, p < 0.001). The kappa value was 0.764 for mrPSM1 and 0.776 for mrPSM2. Decision curve analysis showed a higher net benefit for mrPSM2. CONCLUSION: The proposed grading systems based on MRI could benefit the risk stratification of PSM and are easily interpretable. CRITICAL RELEVANCE STATEMENT: The proposed mrPSM grading systems for preoperative prediction of surgical margin status after radical prostatectomy are simplified compared to a previous model and show high specificity for identifying the risk of positive surgical margin, which might benefit the management of prostate cancer. KEY POINTS: • CCL ≥ 20 mm, apex abutting, and EPE were important MRI features for PSM. • Our proposed MRI-based grading systems showed the possibility to predict PSM with high specificity. • The MRI-based grading systems might facilitate a structured risk evaluation of PSM.

Development and acceptability validation of a deep learning-based tool for whole-prostate segmentation on multiparametric MRI: a multicenter study.

Background: Accurate whole prostate segmentation on magnetic resonance imaging (MRI) is important in the management of prostatic diseases. In this multicenter study, we aimed to develop and evaluate a clinically applicable deep learning-based tool for automatic whole prostate segmentation on T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI). Methods: In this retrospective study, 3-dimensional (3D) U-Net-based models in the segmentation tool were trained with 223 patients who underwent prostate MRI and subsequent biopsy from 1 hospital and validated in 1 internal testing cohort (n=95) and 3 external testing cohorts: PROSTATEx Challenge for T2WI and DWI (n=141), Tongji Hospital (n=30), and Beijing Hospital for T2WI (n=29). Patients from the latter 2 centers were diagnosed with advanced prostate cancer. The DWI model was further fine-tuned to compensate for the scanner variety in external testing. A quantitative evaluation, including Dice similarity coefficients (DSCs), 95% Hausdorff distance (95HD), and average boundary distance (ABD), and a qualitative analysis were used to evaluate the clinical usefulness. Results: The segmentation tool showed good performance in the testing cohorts on T2WI (DSC: 0.922 for internal testing and 0.897-0.947 for external testing) and DWI (DSC: 0.914 for internal testing and 0.815 for external testing with fine-tuning). The fine-tuning process significantly improved the DWI model's performance in the external testing dataset (DSC: 0.275 vs. 0.815; P<0.01). Across all testing cohorts, the 95HD was <8 mm, and the ABD was <3 mm. The DSCs in the prostate midgland (T2WI: 0.949-0.976; DWI: 0.843-0.942) were significantly higher than those in the apex (T2WI: 0.833-0.926; DWI: 0.755-0.821) and base (T2WI: 0.851-0.922; DWI: 0.810-0.929) (all P values <0.01). The qualitative analysis showed that 98.6% of T2WI and 72.3% of DWI autosegmentation results in the external testing cohort were clinically acceptable. Conclusions: The 3D U-Net-based segmentation tool can automatically segment the prostate on T2WI with good and robust performance, especially in the prostate midgland. Segmentation on DWI was feasible, but fine-tuning might be needed for different scanners.

Application of deep learning reconstruction of ultra-low-dose abdominal CT in the diagnosis of renal calculi.

BACKGROUND: Renal calculi are a common and recurrent urological disease and are usually detected by CT. In this study, we evaluated the diagnostic capability, image quality, and radiation dose of abdominal ultra-low-dose CT (ULDCT) with deep learning reconstruction (DLR) for detecting renal calculi. METHODS: Sixty patients with suspected renal calculi were prospectively enrolled. Low-dose CT (LDCT) images were reconstructed with hybrid iterative reconstruction (LD-HIR) and was regarded as the standard for stone and lesion detection. ULDCT images were reconstructed with HIR (ULD-HIR) and DLR (ULD-DLR). We then compared stone detection rate, abdominal lesion detection rate, image quality and radiation dose between LDCT and ULDCT. RESULTS: A total of 130 calculi were observed on LD-HIR images. Stone detection rates of ULD-HIR and ULD-DLR images were 93.1% (121/130) and 95.4% (124/130). A total of 129 lesions were detected on the LD-HIR images. The lesion detection rate on ULD-DLR images was 92.2%, with 10 cysts < 5 mm in diameter missed. The CT values of organs on ULD-DLR were similar to those on LD-HIR and lower than those on ULD-HIR. Signal-to-noise ratio was highest and noise lowest on ULD-DLR. The subjective image quality of ULD-DLR was similar to that of LD-HIR and better than that of ULD-HIR. The effective radiation dose of ULDCT (0.64 ± 0.17 mSv) was 77% lower than that of LDCT (2.75 ± 0.50 mSv). CONCLUSION: ULDCT combined with DLR could significantly reduce radiation dose while maintaining suitable image quality and stone detection rate in the diagnosis of renal calculi.

MicroRNAs-mediated regulation of glucose transporter (GLUT) expression in glioblastoma.

Current knowledge about the role of microRNAs (miRNAs) in tumor glucose metabolism is growing, and a number of studies regularly confirm the impact miRNAs can have on glucose metabolism reprogramming in tumors. However, there remains a lack of understanding of the broader perspective on the role of miRNAs in energy reprogramming in glioblastoma. An important role in the metabolism of glucose is played by carrier proteins that ensure its transmembrane movement. Carrier proteins in mammalian cells are glucose transporters (GLUTs). In total, 12 types of GLUTs are distinguished, differing in localization, affinity for glucose and ability to regulate. The fact of increased consumption of glucose in tumors compared to non-proliferating normal tissues is known. Tumor cells need glucose to ensure their survival and growth, so the type of transport proteins like GLUT are critical for them. Previous studies have shown that GLUT-1 and GLUT-3 may play an important role in the development of some types of malignant tumors, including glioblastoma. In addition, there is evidence of how GLUT-1 and GLUT-3 expression is regulated by miRNAs in glioblastoma. Thus, the aim of this study is to highlight the role of specific miRNAs in modulating GLUT levels in order to take into account the use of miRNAs expression modulators as a useful strategy to increase the sensitivity of glioblastoma to current therapies.

Functions of the bone morphogenetic protein signaling pathway through non-coding RNAs.

Bone morphogenetic proteins (BMPs) are proteins of the transforming growth factor-ß (TGF-ß) family, which plays an important role in the formation of skeletal and cartilage tissue and their regeneration. BMPs play a key role in the formation of new blood vessels and promote the migration, proliferation, and differentiation of mesenchymal stem cells (MSCs) into chondroblasts and osteoblasts. It is known that malfunction of BMPs signaling can cause a disease state. Epigenetic regulation of expression plays a key role in the control of many cellular processes. Important participants in this regulation are non-coding RNAs (ncRNAs), which are RNA molecules that are not translated into proteins. The best known of these are microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs). In addition, the results of many studies make it possible to establish an unambiguous functional relationship between these ncRNAs. Being involved in the regulation of a large number of target genes responsible for the life of the cell, miRNAs, lncRNAs, and circRNAs are essential for the normal development and functioning of the body, and the violation of their functions accompanies the development of many pathophysiological processes including oncogenesis. In the present review, we discuss different insights into the regulation of BMPs signaling pathway by miRNAs, lncRNAs and circRNAs governed.

Deep Learning on Enhanced CT Images Can Predict the Muscular Invasiveness of Bladder Cancer.

BACKGROUND: Clinical treatment decision making of bladder cancer (BCa) relies on the absence or presence of muscle invasion and tumor staging. Deep learning (DL) is a novel technique in image analysis, but its potential for evaluating the muscular invasiveness of bladder cancer remains unclear. The purpose of this study was to develop and validate a DL model based on computed tomography (CT) images for prediction of muscle-invasive status of BCa. METHODS: A total of 441 BCa patients were retrospectively enrolled from two centers and were divided into development (n=183), tuning (n=110), internal validation (n=73) and external validation (n=75) cohorts. The model was built based on nephrographic phase images of preoperative CT urography. Receiver operating characteristic (ROC) curves were performed and the area under the ROC curve (AUC) for discrimination between muscle-invasive BCa and non-muscle-invasive BCa was calculated. The performance of the model was evaluated and compared with that of the subjective assessment by two radiologists. RESULTS: The DL model exhibited relatively good performance in all cohorts [AUC: 0.861 in the internal validation cohort, 0.791 in the external validation cohort] and outperformed the two radiologists. The model yielded a sensitivity of 0.733, a specificity of 0.810 in the internal validation cohort and a sensitivity of 0.710 and a specificity of 0.773 in the external validation cohort. CONCLUSION: The proposed DL model based on CT images exhibited relatively good prediction ability of muscle-invasive status of BCa preoperatively, which may improve individual treatment of BCa.

Exosomal miR-2276-5p in Plasma Is a Potential Diagnostic and Prognostic Biomarker in Glioma.

INTRODUCTION: Exosomal microRNAs (miRNAs) play an essential role in near and distant intercellular communication and are potential diagnostic and prognostic biomarkers for various cancers. This study focused on evaluation of exosomal miR-2276-5p in plasma as a diagnostic and prognostic biomarker for glioma. METHODS: Plasma exosomes from 124 patients with glioma and 36 non-tumor controls were collected and subjected to quantitative real-time polymerase chain reaction (qRT-PCR) analysis for the exosomal miR-2276-5p expression. Bioinformatic analyses were performed to identify a gene target, and CGGA and TCGA databases were checked for evaluation of prognostic relevance. RESULTS: The exosomal miR-2276-5p in glioma patients had a significantly decreased expression, compared with non-glioma patients (p < 0.01). Receiver operating characteristics (ROC) curve analyses were observed to regulate the diagnostic sensitivity and specificity of miR-2276-5p in glioma; the area under the curve (AUC) for miR-2276-5p was 0.8107. The lower expression of exosomal miR-2276-5p in patients with glioma correlated with poorer survival rates. RAB13 was identified as the target of miR-2276-5p which was high in glioma patients, especially those with higher tumor grades and correlated with poor survival. CONCLUSION: The circulating exosomal miR-2276-5p is significantly reduced in the plasma of glioma patients, and thus, it could be a potential biomarker for patients with glioma for diagnostic and/or prognostic purposes.

Comparison of PI-RADS version 2.1 and PI-RADS version 2 regarding interreader variability and diagnostic accuracy for transition zone prostate cancer.

PURPOSE: To compare the diagnostic performance of PI-RADS version 2.1 (PI-RADS v2.1) and PI-RADS v2 for transition zone prostate cancer (TZPC), and analyse its performance for readers with different experience levels. METHODS: Eighty-five patients with suspected prostate cancer who underwent biopsy after MRI scan between January and December 2017 were retrospectively enrolled. One junior radiologist (reader 1, 1 year of experience in using PI-RADS v2) and one senior radiologist (reader 2, 6 years of experience) independently reviewed and assigned a score for each lesion according to PI-RADS v2.1 and v2. The template-guided transperineal prostate biopsy was used for standard of reference. To compare the diagnostic performance of the two methods, the AUC was calculated. The sensitivity, specificity, and accuracy were calculated at predefined positive values (PI-RADS ≥ 3). The interreader agreement and frequency of prostate cancer for each PI-RADS category were also calculated. RESULTS: Among the 85 patients, 27 had prostate cancers, and 25 were clinically significant prostate cancer (csPCa). The AUC values for diagnosing clinically significant prostate cancer significantly increased with PI-RADS v2.1 for reader 2 (0.766 vs. 0.902, P = 0.009). The specificity and accuracy for both readers also increased with PI-RADS v2.1 (specificity: reader 1, 41.7% vs. 78.3% and reader 2, 33.3% vs. 81.7%; accuracy: reader 1, 52.9% vs. 76.5% and reader 2, 48.2% vs. 83.5%, all P < 0.05). The interreader agreement was good for both versions. The percentage of prostate cancer decreased in lower PI-RADS categories (PI-RADS 2) and increased in higher PI-RADS categories (PI-RADS 3 ~ 4). CONCLUSION: Compared with PI-RADS v2, PI-RADS v2.1 may improve radiologists' diagnostic performance for TZPC.

Recommendations for Surgery During the Novel Coronavirus (COVID-19) Epidemic.

The whole world is going through an unprecedented period during the pandemic of COVID-19. This pandemic has affected all aspects of daily life with far-reaching implications, especially in most aspects of healthcare. Practice of surgery across the globe is in a standstill as of now. When we restart surgical practices across world, we have to bring new protocols and practices in place to combat the transmission. This article discusses the major changes in surgical practice, which need to be brought in. This article is based on scientific information about transmission of virus and experiences of some of the authors from China, a country which successfully dealt with and contained the virus outbreak.

BMP8A promotes survival and drug resistance via Nrf2/TRIM24 signaling pathway in clear cell renal cell carcinoma.

There is increasing evidence that bone morphogenetic proteins (BMP) are involved in the proliferation and drug tolerance of kidney cancer. However, the molecular mechanism of BMP8A in renal cell proliferation and drug tolerance is not clear. Here we showed that BMP8A was highly expressed in renal cell carcinoma, which suggests a poor prognosis of ccRCC. Promotion of cell proliferation and inhibition of apoptosis were detected by CCK-8 assay, Trypan Blue staining, flow cytometry and bioluminescence. BMP8A promoted resistance of As2 O3 by regulating Nrf2 and Wnt pathways in vitro and in vivo. Mechanistically, BMP8A enhanced phosphorylation of Nrf2, which, in turn, inhibited Keap1-mediated Nrf2 ubiquitination and, ultimately, promoted nuclear translocation and transcriptional activity of Nrf2. Nrf2 regulates the transcription of TRIM24 detected by ChIP-qPCR. BMP8A was highly expressed in ccRCC, which suggests a poor prognosis. BMP8A was expected to be an independent prognostic molecule for ccRCC. On the one hand, activated Nrf2 regulated reactive oxygen balance, and on the other hand, by regulating the transcription level of TRIM24, it was involved in the regulation of the Wnt pathway to promote the proliferation, invasion and metastasis of ccRCC and the resistance of As2 O3 . Taken together, our findings describe a regulatory axis where BMP8A promotes Nrf2 phosphorylation and activates TRIM24 to promote survival and drug resistance in ccRCC.

Inhibition of MicroRNA-381 Promotes Tumor Cell Growth and Chemoresistance in Clear-Cell Renal Cell Carcinoma.

BACKGROUND MicroRNA-381 (miR-381) is proven to be involved in many human tumors. Bioinformatics prediction suggests that miR-381 is decreased in renal cell carcinoma. However, its biological functions in clear-cell renal cell carcinoma (ccRCC) remain largely unknown. The present research aimed to evaluate miR-381 expression in renal cancer tissues and its effects on cell proliferation, growth, migration, and chemoresistance. MATERIAL AND METHODS Sixty pairs of ccRCC and the adjacent non-tumor specimens were collected during routine therapeutic surgery. Quantitative real-time PCR (qRT-PCR) assay was employed to examine miR-381 expression in the ccRCC tissues and the associated adjacent tissues (the normal tissues adjacent to tumor tissues). Cell transfection assay and Thiazolyl Blue Tetrazolium Bromide (MTT) assay were utilized to observe effects of miR-381 on the cell proliferation, growth, invasion, and chemoresistance in the Caki-1 cell line and 786-O cell line. Flow cytometry was used to assess cell apoptosis. Caki-1 cell and 786-O cell Xenograft BALB/c mouse models were established. RESULTS miR-381 expression was downregulated in ccRCC tissues in vivo and in cell lines in vitro. Downregulation of miR-381 promoted growth of cells and restrained the ccRCC cell apoptosis. Increased miR-381 combined with Ci and Pa suppressed the proliferation and enhanced the anti-tumor effects of Ci and Pa at tolerated concentrations in vitro. miR-381 inhibition promoted chemoresistance in vitro. CONCLUSIONS miR-381 levels were significantly downregulated in renal cancer tissues and miR-381 inhibition promoted tumor cell growth, migration, and chemoresistance.

Novel long noncoding RNA OTUD6B-AS1 indicates poor prognosis and inhibits clear cell renal cell carcinoma proliferation via the Wnt/ß-catenin signaling pathway.

BACKGROUND: The long noncoding RNA (lncRNA) OTUD6B antisense RNA 1 (OTUD6B-AS1) is oriented in an antisense direction to the protein-coding gene OTUD6B on the opposite DNA strand. TCGA database data show that the expression of the lncRNA OTUD6B-AS1 is downregulated and that OTUD6B-AS1 acts as an antioncogene in a variety of tumors. However, the expression and biological functions of the lncRNA OTUD6B-AS1 are still unknown in tumors, including clear cell renal cell carcinoma (ccRCC). METHODS: The expression level of OTUD6B-AS1 was measured in 75 paired human ccRCC tissue and corresponding adjacent normal renal tissue samples. The correlations between the OTUD6B-AS1 expression level and clinicopathological features were evaluated using the chi-square test. The effects of OTUD6B-AS1 on ccRCC cells were determined via MTT assay, clone formation assay, transwell assay, and flow cytometry. Furthermore, the impact of OTUD6B-AS1 overexpression on the activation of the Wnt/ß-catenin signaling pathway was investigated. Finally, ACHN cells with OTUD6B-AS1 overexpression were subcutaneously injected into nude mice to evaluate the influence of OTUD6B-AS1 on tumor growth in vivo. RESULTS: In this study, we found that the expression of the lncRNA OTUD6B-AS1 was downregulated in ccRCC tissue samples and that patients with low OTUD6B-AS1 expression had shorter overall survival than patients with high OTUD6B-AS1 expression, which showed that the different expression level of OTUD6B-AS1 indirectly correlated with survival of patients. Lentivirus-mediated OTUD6B-AS1 overexpression significantly decreased the proliferation of ccRCC cells and promoted the apoptosis of the cells. Furthermore, OTUD6B-AS1 overexpression partly inhibited cell migration and invasion. The overexpression of OTUD6B-AS1 decreased the activity of the Wnt/ß-catenin pathway and suppressed the expression of epithelial-to-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and Snail) in ccRCC cells. In addition, compared with the parental ACHN cells, OTUD6B-AS1-overexpressing ACHN cells injected into nude mice exhibited decreased tumor growth in vivo. CONCLUSIONS: Taken together, our findings present a road map for targeting the newly identified lncRNA OTUD6B-AS1 to suppress ccRCC progression in cell lines, and these results elucidate a novel potential therapeutic target for ccRCC treatment.

α-1,2-Mannosidase MAN1C1 Inhibits Proliferation and Invasion of Clear Cell Renal Cell Carcinoma.

Background: This study investigated the biological function of the gene MAN1C1 α-mannosidase in renal cell carcinoma. It has been reported that MAN1C1 is probably a potential tumor suppressor gene in Wilms. However, the role of MAN1C1 in human clear cell renal cell carcinoma (ccRCC) has not been reported. Methods: In this study, MAN1C1 gene over-expression was used to transfect human renal cancer cell lines 786-O and OS-RC-2 to study apoptosis and the underlying mechanisms which influence epithelial-mesenchymal transition. Results: MAN1C1 was down-regulated in ccRCC and related to the clinicopathological factors and prognosis of ccRCC. We revealed that over-expression MAN1C1 showed anti-tumor effect by inducing apoptosis, as determined by Cell Counting Kit-8 (CCK-8) assay, cell cycle analysis, and western blot analysis. What's more, MAN1C1 over-expression remarkably increased the ratio of Bax/Bcl-2 and inhibited epithelial-mesenchymal transition by increasing the expression of E-CA. In addition, the ratio of Bax/Bcl-2 and E-CA were also increased in MAN1C1 gene over-expression renal cancer cells compared with the control cells. Conclusion: We find that re-expression of silenced MAN1C1 in ccRCC cell lines inhibited cell viability, colony formation, induced apoptosis, suppressed cell invasion and migration. In conclusion, MAN1C1 is a novel functional tumor suppressor in renal carcinogenesis. This is the first time that the function of MAN1C1 gene has been verified in the renal tumor tissue so far.

MicroRNA-195 protection against focal cerebral ischemia by targeting CX3CR1.

OBJECTIVEIt has been reported that microRNA-195 (miR-195) protects against chronic brain injury induced by chronic brain hypoperfusion. However, neither the expression profile of miR-195 nor its potential role during acute ischemic stroke has been investigated. In this study, the authors' aim was to verify the mechanism of miR-195 in acute ischemic stroke.METHODSThe plasma levels of miR-195 expression were assessed using real-time PCR in 96 patients with acute ischemic stroke, and the correlation with the National Institutes of Health Stroke Scale score was evaluated. In addition, cerebral infarct volume, neurological score, and levels of miR-195 and CX3CL1/CX3CR1 mRNA and protein expression were assessed in mice subjected to middle cerebral artery occlusion (MCAO) with or without intra-cerebroventricular infusion of lentiviral vector. The inflammatory cytokines tumor necrosis factor-α (TNFα), interleukin (IL)-1ß, and IL-6 of mouse brains after MCAO and BV2 cells treated with oxygen-glucose deprivation were measured using enzyme-linked immunosorbent assay, and apoptotic proteins were examined by Western blotting. Direct targeting of CX3CL1/CX3CR1 by miR-195 was determined by immunoblotting and dual luciferase assay.RESULTSIn ischemic stroke patients, miR-195 was significantly downregulated and expression levels of miR-195 in these patients negatively correlated with the National Institutes of Health Stroke Scale score. In mice after MCAO, miR-195 overexpression decreased infarct volume, alleviated neurological deficits, and most importantly, suppressed an inflammatory response. Meanwhile, miR-195 suppressed the expression of the inflammatory cytokines TNFα, IL-1ß, and IL-6 in vitro and in vivo. The authors further discovered that both CX3CL1 and CX3CR1 are direct targets of miR-195, but miR-195 exerts neuroprotective roles mainly through inhibiting CX3CR1-mediated neuroinflammation and subsequent neuronal cell apoptosis.CONCLUSIONSTaken together, these findings suggest that miR-195 promotes neuronal cell survival against chronic cerebral ischemic damage by inhibiting CX3CR1-mediated neuroinflammation. This indicates that miR-195 may represent a novel target that regulates neuroinflammation and brain injury, thus offering a new treatment strategy for cerebral ischemic disorders.

Cornea Full-field Displacement and Strain Measurement in Vivo Using Three-dimensional Digital Image Correlation.

SIGNIFICANCE: Corneal biomechanics are becoming increasingly important for clinical evaluation and diagnosis, such as in refractive surgery, glaucoma, and keratoconus. We developed and used a new technique to measure the full-field displacement and strain of the cornea under elevated intraocular pressure in vivo. PURPOSE: In this study, we propose a three-dimensional digital image correlation method for the determination of corneal biomechanical properties. METHODS: Corneal deformation change on the rabbit eyeball was investigated under different inflation conditions with intraocular pressure levels of 2.3, 3.3, 5.3, and 6.9 kPa in vivo. RESULTS: The proposed method was able to measure the displacement of the corneal surface and to construct real-time full-field three-dimensional deformation vector fields and strain mapping. The results show that the strain distribution is not uniform on the corneal surface at each intraocular pressure level. Compression strains, rather than extensile strains, are dominant at the corneal apex region. CONCLUSIONS: This technique has the potential to be used as an assistive tool for the determination of corneal biomechanical properties in ophthalmologic investigations.

Nitazoxanide, an antiprotozoal drug, inhibits late-stage autophagy and promotes ING1-induced cell cycle arrest in glioblastoma.

Glioblastoma is the most common and aggressive primary brain tumor in adults. New drug design and development is still a major challenge for glioma treatment. Increasing evidence has shown that nitazoxanide, an antiprotozoal drug, has a novel antitumor role in various tumors and exhibits multiple molecular functions, especially autophagic regulation. However, whether nitazoxanide-associated autophagy has an antineoplastic effect in glioma remains unclear. Here, we aimed to explore the underlying molecular mechanism of nitazoxanide in glioblastoma. Our results showed that nitazoxanide suppressed cell growth and induced cell cycle arrest in glioblastoma by upregulating ING1 expression with a favorable toxicity profile. Nitazoxanide inhibited autophagy through blockage of late-stage lysosome acidification, resulting in decreased cleavage of ING1. A combination with chloroquine or Torin1 enhanced or impaired the chemotherapeutic effect of nitazoxanide in glioblastoma cells. Taken together, these findings indicate that nitazoxanide as an autophagy inhibitor induces cell cycle arrest in glioblastoma via upregulated ING1 due to increased transcription and decreased post-translational degradation by late-stage autophagic inhibition.