TDO2 promotes bladder cancer progression via AhR-mediated SPARC/FILIP1L signaling.

The enzyme tryptophan 2,3-dioxygenase (TDO2) has been implicated in the dysregulation across a variety of human cancers. Despite this association, the implications of TDO2 in the progression of bladder cancer have eluded thorough understanding. In this study, we demonstrate that TDO2 expression is notably elevated in bladder cancer tissues and serves as an unfavorable prognostic factor for overall survival. Through a series of biological functional assays, we have determined that TDO2 essentially enhances cell proliferation, metastatic potential, and imparts a decreased sensitivity to the chemotherapeutic agent cisplatin. Our mechanistic investigations reveal that TDO2 augments aryl hydrocarbon receptor (AhR) signaling pathways and subsequently upregulates the expression of SPARC and FILIP1L. Importantly, we have identified a positive correlation between TDO2 levels and the basal/squamous subtype of bladder cancer, and we provide evidence to suggest that TDO2 expression is modulated by the tumor suppressors RB1 and TP53. From a therapeutic perspective, we demonstrate that the targeted inhibition of TDO2 with the molecular inhibitor 680C91 markedly attenuates tumor growth and metastasis while concurrently enhancing the efficacy of cisplatin. These findings open a new therapeutic avenue for the management of bladder cancer.

LINC00645 inhibits renal cell carcinoma progression by interacting with HNRNPA2B1 to regulate the ROCK1 mRNA stability.

The lncRNA plays an important role in tumorigenesis and the progression of renal cell carcinoma (RCC). LINC00645 is one of the most different expressed lncRNA between RCC and normal renal tissue. However, the regulatory mechanism of LINC00645 in RCC remains unknown. Our results indicated that LINC00645 inhibited RCC proliferation, migration, and invasion. Mechanistically, HNRNPA2B1 directly bound to ROCK1 mRNA and strengthened its stability. LINC00645 competitively bound to the RRM1 domain, which is responsible for interacting with ROCK1 mRNA, reducing ROCK1 mRNA level by affecting posttranscriptional destabilization. The expression of LINC00645 was significantly reduced in RCC cells, significantly upregulating ROCK1 by abolishing the interaction with HNRNPA2B1, finally promoting RCC proliferation, migration, and invasion. Moreover, RCC cells with lower LINC00645 expression were more sensitive to the ROCK1 inhibitor Y-27632. Our study indicates that decreased expression of LINC00645 promotes the RCC progression via HNRNPA2B1/ROCK1 axis, providing a promising treatment strategy for RCC patients with decreased LINC00645 expression.

Investigating the Impact of Substrate Preheating on the Thermal Flow and Microstructure of Laser Cladding of Nickel-Based Superalloy.

The preheating of the substrate in laser additive superalloys can reduce residual stress and minimize cracking. However, this preheating process can lead to changes in the heat transfer conditions, ultimately affecting the resulting microstructure and mechanical properties. In order to explore the influence of substrate preheating on the formation of laser cladding, this research focuses on investigating the characteristics of Inconel 718, a nickel-based superalloy, as the subject of study. To simulate the temperature and flow field of laser cladding, a 3D computational fluid dynamics (CFD) model is employed. By varying the initial preheating conditions, an investigation is conducted into the distribution of the temperature field under different parameters. This leads to the acquisition of varying temperature gradients, G, and solidification speeds, R. Subsequently, an analysis is carried out on both the flow field and solidification microstructure in the melt pool. The results demonstrate that the preheating of the substrate results in a slower cooling rate, ultimately leading to the formation of a coarser microstructure.

Prediction of Primary Dendrite Arm Spacing of the Inconel 718 Deposition Layer by Laser Cladding Based on a Multi-Scale Simulation.

Primary dendrite arm spacing (PDAS) is a crucial microstructural feature in nickel-based superalloys produced by laser cladding. In order to investigate the effects of process parameters on PDAS, a multi-scale model that integrates a 3D transient heat and mass transfer model with a quantitative phase-field model was proposed to simulate the dendritic growth behavior in the molten pool for laser cladding Inconel 718. The values of temperature gradient (G) and solidification rate (R) at the S/L interface of the molten pool under different process conditions were obtained by multi-scale simulation and used as input for the quantitative phase field model. The influence of process parameters on microstructure morphology in the deposition layer was analyzed. The result shows that the dendrite morphology is in good agreement with the experimental result under varying laser power (P) and scanning velocity (V). PDAS was found to be more sensitive to changes in laser scanning velocity, and as the scanning velocity decreased from 12 mm/s to 4 mm/s, the PDAS increased by 197% when the laser power was 1500 W. Furthermore, smaller PDAS can be achieved by combining higher scanning velocity with lower laser power.

Ginsenoside Rd attenuated hyperglycemia via Akt pathway and modulated gut microbiota in streptozotocin-induced diabetic rats.

Ginsenoside Rd is a protopanaxadiol abundant in Panax ginseng and Panax notoginseng. It has been reported that ginsenoside Rd possesses various health benefits, such as anti-diabetic, anti-tumor and anti-inflammatory. This work explored the effects of ginsenoside Rd on hyperglycemia and gut microbiota in streptozotocin-induced diabetic rats. Results showed that 5-week ginsenoside Rd (20 mg/kg) treatment significantly improved hyperglycemia in diabetic rats. Besides, ginsenoside Rd promoted glycogen synthesis via activating Akt pathway. It also inhibited hepatic gluconeogenesis, which was associated with inhibiting phosphoenolpyruvate carboxykinase and glucose-6-phosphatase. We further found that ginsenoside Rd treatment increased the diversity of gut microbiota, increased the abundance of beneficial bacteria, such as SMB53, rc4-4 and Ruminococcus, and reduced the abundance of conditional pathogenic bacteria. These results indicated that ginsenoside Rd has the potential for diabetic intervention.

Zeaxanthin prevents ferroptosis by promoting mitochondrial function and inhibiting the p53 pathway in free fatty acid-induced HepG2 cells.

Non-alcoholic fatty liver disease (NAFLD) is a common liver disorder worldwide and a risk factor for obesity and diabetes. Emerging evidence has shown that ferroptosis is involved in the progression of NAFLD. Zeaxanthin (ZEA) is a carotenoid found in human serum. It has been reported that ZEA can ameliorate obesity, prevent age-related macular degeneration, and protect against non-alcoholic steatohepatitis. However, no study has focused on the protective effects of ZEA against NAFLD. In this study, free fatty acid (FFA) induced HepG2 cells were used as a cell model for NAFLD. Our results suggest that ZEA exerts antioxidative and anti-inflammatory effects in FFA-induced HepG2 cells. Moreover, ZEA acted as a ferroptosis inhibitor, significantly reducing reactive oxygen species (ROS) generation and iron overload and improving mitochondrial dysfunction in FFA-induced HepG2 cells. In addition, ZEA downregulated the expression of p53 and modulated downstream targets, such as GPX4, SLC7A11, SAT1, and ALOX15, which contributed to the reduction in cellular lipid peroxidation. Our findings suggest that ZEA has the potential for NAFLD intervention.

Zeaxanthin remodels cytoplasmic lipid droplets via ß3-adrenergic receptor signaling and enhances perilipin 5-mediated lipid droplet-mitochondrion interactions in adipocytes.

Cytoplasmic lipid droplets (LDs), which are remarkably dynamic, neutral lipid storage organelles, play fundamental roles in lipid metabolism and energy homeostasis. Both the dynamic remodeling of LDs and LD-mitochondrion interactions in adipocytes are effective mechanisms to ameliorate obesity and related comorbidities. Zeaxanthin (ZEA) is a natural carotenoid and has beneficial effects on anti-obesity. However, the underlying mechanisms of ZEA on LD modulation are still unclear. In the present study, ZEA efficiently inhibited LD accumulation and attenuated adipocyte proliferation by arresting the cell cycle. ZEA drove transcriptional alterations to reprogram a lipid oxidative metabolism phenotype in mature 3T3-L1 adipocytes. ZEA significantly decreased the TAG and FA content and modulated the dynamic alterations of LDs by upregulating the expression of lipases and the LD-mitochondrion contact site protein, perilipin 5 (PLIN5), and downregulating the LD fusion protein, fat-specific protein 27 (FSP27). Mechanistically, ZEA stimulated LD remodeling and ameliorated mitochondrial defects caused by large and unilocular LD accumulation by activating ß3-adrenergic receptor (ß3-AR) signaling. Furthermore, the knockdown of PLIN5 impaired the LD-mitochondrion interactions, thereby disrupting the role of ZEA in promoting mitochondrial fatty acid oxidation and respiratory chain operation. Collectively, the present study demonstrates that ZEA induces LD structural and metabolic remodeling by activating ß3-AR signaling and enhances PLIN5-mediated LD-mitochondrion interactions in hypertrophic white adipocytes, thereby enhancing oxidative capacity, and has the potential as a nutritional intervention for the prevention and treatment of obesity and associated metabolic syndrome.

Thermal and Mechanical Variation Analysis on Multi-Layer Thin Wall during Continuous Laser Deposition, Continuous Pulsed Laser Deposition, and Interval Pulsed Laser Deposition.

Direct laser deposition (DLD) is widely used in precision manufacturing, but the process parameters (e.g., laser power, scanning patterns) easily lead to changes in dimensional accuracy and structural properties. Many methods have been proposed to analyze the principle of distortion and residual stress generation, but it is difficult to evaluate the involvement of temperature and stress in the process of rapid melting and solidification. In this paper, a three-dimensional finite element model is established based on thermal-mechanical relationships in multilayer DLD. Differences in temperature and residual stress between continuous laser deposition (CLD) and pulsed laser deposition (PLD) are compared with the numerical model. To validate the relationship, the temperature and residual stress values obtained by numerical simulation are compared with the values obtained by the HIOKI-LR8431 temperature logger and the Pulstec µ-X360s X-ray diffraction (XRD) instrument. The results indicate that the temperature and residual stress of the deposition part can be evaluated by the proposed simulation model. The proposed PLD process, which includes continuous pulsed laser deposition (CPLD) and interval pulsed laser deposition (IPLD), were found more effective to improve the homogeneity of temperature and residual stress than the CLD process. This study is expected to be useful in the distortion control and microstructure consistency of multilayer deposited parts.

Zeaxanthin ameliorates obesity by activating the ß3-adrenergic receptor to stimulate inguinal fat thermogenesis and modulating the gut microbiota.

The stimulation of fat thermogenesis and modulation of the gut microbiota are promising therapeutic strategies against obesity. Zeaxanthin (ZEA), a carotenoid plant pigment, has been shown to prevent various diseases; however, the therapeutic mechanism for obesity remains unclear. Herein, whether ZEA improves obesity by activating the ß3-adrenergic receptor (ß3-AR) to stimulate white adipose tissue (WAT) thermogenesis and modulating the gut microbiota was investigated. C57BL6/N mice were fed a high-fat diet (HFD) supplemented with ZEA for 22 weeks. ZEA treatment reduced body weight, fat weight, adipocyte hypertrophy, liver weight, and lipid deposition, and improved dyslipidaemia, serum GPT, GOT, leptin, and irisin levels, glucose intolerance, and insulin resistance in HFD-fed mice. Mechanistically, ZEA treatment induced the expression of ß3-AR and thermogenic factors, such as PRDM16, PGC-1α, and UCP1, in inguinal WAT (iWAT) and brown adipose tissue. ZEA treatment stimulated iWAT thermogenesis through the synergistic cooperation of key organelles, which manifested as an increased expression of lipid droplet degradation factors (ATGL, CGI-58 and pHSL), mitochondrial biogenesis factors (Sirt1, Nrf2, Tfam, Nampt and Cyt-C), peroxisomal biogenesis factors (Pex16, Pex19 and Pmp70), and ß-oxidation factors (Cpt1, Cpt2, Acadm and Acox1). The thermogenic effect of ZEA was abolished by ß3-AR antagonist (SR59230A) treatment. Additionally, dietary supplementation with ZEA reversed gut microbiota dysbiosis by regulating the abundance of Firmicutes, Clostridia, Proteobacteria, and Desulfovibrio, which were associated with the thermogenesis- and obesity-associated indices by Spearman's correlation analysis. Functional analysis of the gut microbiota indicated that ZEA treatment significantly enriched the lipid metabolism pathways. These results demonstrate that ZEA is a promising multi-target functional food for the treatment of obesity by activating ß3-AR to stimulate iWAT thermogenesis, and modulating the gut microbiota.

Elevational distribution and occurrence of arbuscular mycorrhizal fungi in non-host Carex capillacea.

Little is known about Arbuscular mycorrhizal (AM) fungal colonization and community composition in non-mycorrhizal (NM) plants, especially along elevational gradients. This study explores this question using a NM plant, Carex capillacea, at Mount Segrila, Tibet. Here, C. capillacea, its rhizosphere soil, and the neighboring mycotrophic plant Poa annua were sampled at four elevations to evaluate and compare their AM fungi colonization and communities. The results showed that AM fungal colonization density of C. capillacea was negatively correlated with elevation and biomass of total NM plants per quadrat. AM fungal diversity and community composition between C. capillacea and P. annua showed a similar pattern. In addition, elevation and soil did not significantly influence the AM community in C. capillacea, while they were important abiotic factors for assemblages in rhizosphere soil and P. annua. These findings support that a broad array of AM fungi colonize the root of C. capillacea, and a mycelial network from a co-occurring host plant might shape the AM fungal communities in C. capillacea along the elevation gradient. The co-occurrence patterns of AM fungi associated with non-mycotrophic species and adjacent mycotrophic species have important implications for understanding AM fungal distribution patterns and plant-AM interactions.

Bioinformatics Analysis of GFAP as a Potential Key Regulator in Different Immune Phenotypes of Prostate Cancer.

Tumor immune escape plays an essential role in both cancer progression and immunotherapy responses. For prostate cancer (PC), however, the molecular mechanisms that drive its different immune phenotypes have yet to be fully elucidated. Patient gene expression data were analyzed from The Cancer Genome Atlas-prostate adenocarcinoma (TCGA-PRAD) and the International Cancer Genome Consortium (ICGC) databases. We used a Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) analysis and an unsupervised clustering analysis to identify patient subgroups with distinct immune phenotypes. These distinct phenotypes were then explored for associations for differentially expressed genes (DEGs) and both epigenetic and genetic landscapes. Finally, we used a protein-protein interaction analysis to identify key hub genes. We identified two patient subgroups with independent immune phenotypes associated with the expression of Programmed death-ligand 1 (PD-L1). Patient samples in Cluster 1 (C1) had higher scores for immune-cell subsets compared to Cluster 2 (C2), and C2 samples had higher specific somatic mutations, MHC mutations, and genomic copy number variations compared to C1. We also found additional cluster phenotype differences for DNA methylation, microRNA (miRNA) expression, and long noncoding RNA (lncRNA) expression. Furthermore, we established a 4-gene model to distinguish between clusters by integrating analyses for DEGs, lncRNAs, miRNAs, and methylation. Notably, we found that glial fibrillary acidic protein (GFAP) might serve as a key hub gene within the genetic and epigenetic regulatory networks. These results improve our understanding of the molecular mechanisms underlying tumor immune phenotypes that are associated with tumor immune escape. In addition, GFAP may be a potential biomarker for both PC diagnosis and prognosis.

Upregulated circPDK1 Promotes RCC Cell Migration and Invasion by Regulating the miR-377-3P-NOTCH1 Axis in Renal Cell Carcinoma.

BACKGROUND: Circular RNAs (circRNAs) are novel clusters of endogenous noncoding RNAs (ncRNAs) that are involved in the regulation of multiple biological processes in diverse types of cancers. However, the roles and precise mechanisms of circRNAs in renal cell carcinoma (RCC) occurrence and progression have not been clearly elucidated. METHODS: We identified the aberrantly expressed circRNAs in RCC by high-throughput RNA-seq assay and used qRT-PCR to test the expression level of circRNAs in RCC tissues. Loss-of-function experiments were executed to detect the biological roles of circPDK1 in the RCC cells both in vivo and in vitro. RNA Fish, luciferase reporter assays and Western blotting were used to explore the molecular mechanism of circPDK1 function. All data were expressed as the means ± standard error of the mean (SEM). Student's t-test, one-way ANOVA, Cox regression, an LSD-t-test, Pearson's chi-squared test, a Log-rank test, and linear regression analyses were used to evaluate the group differences. P < 0.05 was considered significant. RESULTS: CircPDK1 was overexpressed in RCC tissues and positively associated with patient tumor metastasis and renal cell invasion. The in vivo functional assays also revealed that circPDK1 drove RCC xenograft metastasis. CircPDK1 was mainly located in the cytoplasm, serving as a sponge of miR-377-3P to regulate RCC invasion and metastasis through NOTCH1 (Notch Homolog 1). Ectopic express of NOTCH1 in RCC cell lines will block the metastasis inhibition effect after circPDK1 knockdown. CONCLUSION: CircPDK1 is aberrantly expressed in RCC and promotes the metastasis of RCC cells mainly through sponging miR-377-3P and reducing its negative regulation of NOTCH1. Thus, circPDK1 may act as a therapeutic target and biomarker for RCC.

Ginsenoside Rg2 inhibits adipogenesis in 3T3-L1 preadipocytes and suppresses obesity in high-fat-diet-induced obese mice through the AMPK pathway.

Ginsenoside Rg2 is one of the specific ginsenosides in red ginseng, and has been reported to exhibit protective effects against neurotoxicity and memory impairment, and also inhibition of hepatic glucose production. However, the effect of Rg2 on the prevention of obesity has not been investigated. In this study, we evaluated the anti-obesity and anti-adipogenic effects of Rg2 in high-fat diet-induced obese mice (HFD mice) and 3T3-L1 preadipocytes. Oral administration of Rg2 (10 mg kg-1) to HFD mice significantly decreased body weight gain, total triglycerides, and free fatty acid levels. In 3T3-L1 preadipocytes, Rg2 (80 µM) inhibited adipocyte differentiation and reduced the accumulation of intracellular lipids. Quantitative PCR and western blot analysis revealed that Rg2 decreased the expression levels of adipogenic transcription factors (PPARγ, C/EBPα, and SREBP1-c), and then regulated target genes such as acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). Rg2 significantly promoted AMP-activated protein kinase (AMPK) both in vivo and in vitro, which is known to suppress adipogenesis. It was also found that pretreating with compound C, a typical inhibitor of AMPK, attenuated the inhibitory effect of Rg2 on AMPK phosphorylation. These findings suggested that Rg2-induced activation of AMPK leads to a decrease in the expression of adipogenic transcription factors, and suppression of adipogenesis in vivo and in vitro. Hence, Rg2 has the potential for the development of healthy foods and the prevention of obesity.

Zeaxanthin promotes mitochondrial biogenesis and adipocyte browning via AMPKα1 activation.

Zeaxanthin (ZEA), a type of oxygenated carotenoid with strong antioxidant activity, has previously been found to exhibit an anti-lipogenesis effect. In the present study, we investigated the effect of ZEA on brown-like adipocyte formation and mitochondrial biogenesis in 3T3-L1 adipocytes. Brown adipocyte-specific markers, mitochondrial biogenesis and oxidative stress, and the involvement of AMP-activated protein kinase (AMPK) α1 were assessed. ZEA treated adipocytes demonstrated a brown-like pattern, with upregulated expression of uncoupling protein 1 (UCP1) and other brown adipocyte markers. In addition, ZEA intervention induced a dramatic increase in mitochondrial DNA (mtDNA) content and in the mRNA levels of genes associated with mitochondrial biogenesis. Furthermore, ZEA attenuated mitochondrial oxidative damage caused by lipid peroxidation in adipocytes, significantly improved the mitochondrial membrane potential (MMP), and scavenged intracellular reactive oxygen species (ROS) and mitochondrial superoxide. Finally, we concluded that AMPKα1 mediated the ZEA-caused inhibition of lipid accumulation and promotion of brown and beige adipocyte-biomarker expression, as the positive effects of ZEA were diminished by Prkaa1 (AMPKα1) knockdown. These findings demonstrated that ZEA promoted the expression of brown and beige adipogenesis markers and mitochondrial biogenesis, which involved AMPKα1 activation, thus contributing to the anti-obesity effects of ZEA.

Long non-coding RNA XIST regulates miR-106b-5p/P21 axis to suppress tumor progression in renal cell carcinoma.

Long non-coding RNAs (lncRNAs) have been demonstrated to exert important roles in cancer development and progression. The biological function of lncRNA X-inactive specific transcript (XIST) in the development of renal cell carcinoma (RCC) and the underlying mechanisms are still largely unknown. In this study, we found that XIST was down-regulated in RCC tissues and cells. Overexpression of XIST significantly suppressed cell proliferation and induced cell G0/G1 arrest in vitro and inhibited tumor growth in vivo. We further found that XIST could directly interact with miR-106b-5p and increase the expression of P21. Thus, XIST positively regulated the expression of P21 through sponging miR-106b-5p, and played a tumor suppressor role in RCC. Moreover, we found that curcumin could regulate XIST/miR-106b-5p/P21 axis in RCC cells. Our study exhibits the role of XIST as a miRNA sponge in RCC and supports the potential application of XIST in RCC therapy.

[Clinical characterization of testicular yolk sac tumor in children and adults].

OBJECTIVE: To compare the clinical characteristics of simple testicular yolk sac tumor (YST) in children with those in adults so as to improve the diagnosis and treatment of the malignance. METHODS: This study included 75 cases of simple testicular YST pathologically confirmed between May 2008 and July 2018, which were divided into groups A (aged <18 years, n = 64) and B (aged ≥18 years, n = 11). We analyzed the clinical data on all the cases and compared the clinical manifestations, laboratory results, pathological findings, clinical stages, treatment methods and prognostic outcomes between the two groups of patients. RESULTS: The patients of group A ranged in age from 6 months to 5 years (ï¼»1.38 ± 0.89ï¼½ yr), with the tumor diameter of 0.9－6.0 (2.48 ± 1.12) cm, while those of group B from 25 to 49 years (median 34 years), with the tumor diameter of 3.5－6.3 (5.16 ± 1.32) cm, most presenting with a painless scrotal mass, 4 (6.2%) in group A and 5 (45.5%) in group B with testis pain. There were statistically significant differences between the two groups in the tumor diameter and initial manifestations (P < 0.05). All the patients were treated by radical high-level spermatectomy and orchiectomy and, in addition, 1 in group A and 3 in group B by retroperitoneal lymph node dissection (RPLND), 24 in the former and 5 in the latter group followed by chemotherapy. Elevated levels of serum alpha-fetoprotein (AFP) were observed in all the cases. Sixty-five of the patients were followed up for 10－78 (52.00 ± 23.78) months, during which 2 cases of simple metastasis, 3 cases of simple relapse, 3 cases of relapse with metastasis and 5 cases of death were found in group A, and 5 cases of simple metastasis, 1 case of simple relapse, 1 case of relapse with metastasis and 4 cases of death in group B. CONCLUSIONS: There are significant differences in the clinical manifestation, biological behavior, treatment and prognosis of testicular YST between children and adults. In children, most of the testicular YST cases are at clinical stage I and preferably treated by radical high-level spermatectomy and orchiectomy with favorable prognosis. In adults, however, the tumor is highly malignant, with high incidences of recurrence and metastasis and poor prognosis, for the treatment of which the first choice is radical high-level spermatectomy and orchiectomy combined with RPLND and chemotherapy.

MicroRNA-212 inhibits the proliferation, migration and invasion of renal cell carcinoma by targeting X-linked inhibitor of apoptosis protein (XIAP).

MicroRNAs have been found to be critical regulator of cancer cell biology. MicroRNA-212 (miR-212) was identified to be a critical cancer-associated microRNA playing either oncogenic functions or tumor suppressive roles in different types of human cancers. In this study, we found that the level of miR-212 in renal cell carcinoma (RCC) tissues was significantly lower than that in adjacent non-tumor tissues. Decreased level of miR-212 was associated with advanced T stage and TNM stage of RCC. The expression of miR-212 was decreased in RCC cell lines as compared with the HK-2 cell line. Overexpression of miR-212 inhibited cell viability, proliferation, migration and invasion of CAKI-2 cells. Knockdown of miR-212 increased cell viability and proliferation, migration and invasion of ACHN cells. In vivo experiments showed that miR-212 inhibited the proliferation and promoted the apoptosis of ACHN cells in nude mice and thus inhibited the in vivo tumor growth of CAKI-2 cells. Furthermore, we confirmed that X-linked inhibitor of apoptosis protein (XIAP) was the downstream target of miR-212. The expression level of miR-212 was negatively correlated with XIAP expression in RCC tissues. Moreover, XIAP mediated the tumor suppressive roles of miR-212 in RCC. Finally, we demonstrated that the aberrant expression of miR-212 and XIAP was evidently correlated with poor prognosis of RCC patients. In all, miR-212 can act as a prognostic biomarker for RCC patients and inhibits the growth and metastasis of RCC cells by inhibiting XIAP.

NDRG2 knockdown promotes fibrosis in renal tubular epithelial cells through TGF-ß1/Smad3 pathway.

Renal fibrosis is a common pathological pathway of various chronic kidney diseases progressing to end-stage renal disease and is characterized by tubular atrophy, fibroblast/myofibroblast activation and excessive deposition of extracellular matrix (ECM). N-Myc downstream-regulated gene-2 (NDRG2) is reported to be associated with liver fibrosis in rats. However, the biological function of NDRG2 in renal fibrosis remains unclear. Therefore, we investigate the effect of NDRG2 on renal fibrosis and the underlying mechanism of NDRG2 in TGF-ß1-induced renal tubular epithelial cells (HK-2). Our results show that TGF-ß1 down-regulates NDRG2 mRNA and protein expression in HK-2 cells. Moreover, NDRG2 knockdown dramatically reduces the TGF-ß1-induced protein and mRNA of E-cadherin and increases the TGF-ß1-induced protein and mRNA expression level of α-SMA, Vimentin, Snail, Col-I, Col-III and FN; this is reversed by NDRG2 overexpression. Furthermore, NDRG2 silencing significantly increases the phosphorylation level of Smad3 (p-Smad3), which is decreased by NDRG2 overexpression, although these have no effect on the protein expression of p-Smad2 and Smad7. In addition, SIS3, a specific inhibitor of Smad3 phosphorylation, partly reverses the effect of NDRG2 knockdown on the protein and mRNA expression of epithelial-mesenchymal transition (EMT) markers and ECM components in TGF-ß1-induced HK-2 cells. Taken together, our results indicate that NDRG2 knockdown promotes renal fibrosis through its effect on the protein and mRNA expression of EMT markers and ECM components by regulating the downstream Smad3 signaling pathway in renal tubular epithelial cells. Modulation of NDRG2 expression might provide a new therapy for renal fibrosis.

Involvement of interstitial cells of Cajal in bladder dysfunction in mice with experimental autoimmune encephalomyelitis.

BACKGROUND: Bladder dysfunction is an important symptom of experimental autoimmune encephalomyelitis (EAE). Our previous study showed that EAE-induced upregulation of the E-prostanoid receptor 3 (EP3) and E-prostanoid receptor 4 (EP4) in the bladder was accompanied by bladder dysfunction. Although many other studies have evaluated the lower urinary tract symptoms in multiple sclerosis, the mechanism remains unclear. OBJECTIVES: To investigate the effects of interstitial cells of Cajal (ICC) on bladder dysfunction in a novel neurogenic bladder model induced by experimental autoimmune encephalomyelitis. MATERIALS AND METHODS: The EAE model was induced by a previously established method, and bladder functions in mice were evaluated. Bladders were harvested for the analysis of ICCs and the genes associated with bladder mechanosensation including pannexin 1 (Panx1) and Gja1 (encoding connexin43) by immunofluorescence and western blotting. The stem cell factor cytokine (SCF) was intraperitoneally injected at the beginning of EAE onset. RESULTS: EAE mice developed profound bladder dysfunction characterized by significant urine retention, increased micturition and decreased urine output per micturition. EAE induced a significant decrease in c-Kit expression and ICCs number. EAE also induced a significant increase in pannexin 1 and connexin43. SCF treatment could ameliorate all of these pathological changes. CONCLUSIONS: ICCs and stem cell factor play an important role in EAE-induced bladder dysfunction, which may be used as therapeutic options in treating patients with multiple sclerosis-related bladder dysfunction.

Introducing the Quill™ device for modified sleeve circumcision with subcutaneous suture: a retrospective study of 70 cases.

OBJECTIVE: The purpose of the study was to evaluate the safety and feasibility of treatment for male circumcision using modified sleeve circumcision and subcuticular suture with the Quill™ device. METHODS: From May 2011 to March 2012, 70 consecutive cases of male circumcision were performed using an alternative technique with the Quill™ device by a single surgeon in our institution. The inclusion and exclusion criteria for the selection process of this procedure were the same as for conventional circumcision. We evaluated the indications and perioperative outcomes. The circumcisions were performed as day-case procedures under local anesthesia. RESULTS: All patients were followed up for a minimum of 3-6 months. The ages ranged from 8 to 68 (mean = 27.0 years, SD = 10). The indications for surgery were either cosmetic (n = 16, 22.9%) or medical [redundant prepuce (n = 36, 51.4%), phimosis (n = 5, 7.1%), paraphimosis (n = 2, 2.9%), balanoposthitis (n = 9, 12.9%), melanoma (n = 1, 1.4%), and condyloma acuminata (n = 1, 1.4%)] (n = 54, 77.1%). The mean operation time in this group was 29 min (19-38 min) when the Quill™ device was used. In all, 3 cases developed complications (4.3%). The final cosmetic result was satisfactory for both the patients and their spouses or parents. CONCLUSION: This study showed that modified sleeve circumcision and subcuticular suture were safe and reliable surgical methods of circumcision that provide a better cosmetic result.