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Purpose: MicroRNAs (miRNAs) post-transcriptionally regulate hundreds of gene targets involved in tumorigenesis thereby controlling vital biological processes, including cellular proliferation, di erentiation and apoptosis. MiRNA pro ling is an emerging tool for the potential early detection of a variety of malignancies. is study was conducyed to assess the feasibility and methodological robustness of quantifying sputum miRNAs, employing quantitative real-time polymerase chain reaction (RT-qPCR) and cluster analysis on an optimized miRNA pro le as a novel approach for the early detection of non-small cell lung cancer (NSCLC).Methods: e relative expressions of 11 miRNAs in sputum (miR-21, miR-145, miR-155, miR-205, miR-210, miR-92, miR-17-5p, miR-143, miR-182, miR-372, and let-7a) in addition to U6 were retrospectively assessed in four NSCLC-positive and four negative controls. Subsequently, a set of ve miRNAs (miR-21, miR-143, miR-155, miR-210, miR-372) was selected because of degree of relatedness observed in the cluster analysis and tested in the same sputum sample set. e ve optimized miRNAs accurately clustered these eight retrospective patients into NSCLC positive cases and negative controls. e ve miRNA panel was then prospectively quanti ed in the sputum of 30 study patients (24 NSCLC cases and six negative controls) in a double-blind fashion to validate a ve miRNA panel using hierarchical cluster analysis.Results: e optimized ve miRNA panel detected NSCLC (83.3% sensitivity and 100% speci city) in 30 prospectively accrued study patients.Conclusion: Sputum miRNA pro ling using cluster analysis is a promising approach for the early detection of non-small cell lung cancer. Further investigation using this approach is warranted.

Our results suggested that HepaCAM acted as a tumor suppressor in prostate cancer. HepaCAM inhibited cell viability and motility which might be through suppressing the nuclear translocation of Androgen Receptor and down-regulating the ERK signaling. Therefore, it was indicated that HepaCAM may be a potential therapeutic target for prostate cancer.

Keywords: bladder cancer, HepaCAM, T24, Wnt/b-catenin Abbreviations: Ad, adenvirus; HepaCAM, hepatocyte cell adhesion molecule.We previously established that hepatocyte cell adhesion molecule (hepaCAM), a typical structure of immunoglobulin (Ig)-like adhesion molecules, inhibited the proliferation and the progression of cultured human bladder cancer cells. As increasing evidence reveals that aberrant activation of canonical Wnt pathway is involved in the pathogenesis of bladder cancer, and b-catenin serves as a pivotal molecule of Wnt pathway. Then, we explored whether the antiproliferation effect of hepaCAM was associated with Wnt/b-catenin pathway in human bladder cancer cells. The negative correlation between hepaCAM and b-catenin in transitional cell carcinoma of bladder (TCCB) was found. Follow by, studied the effect of hepaCAM on the key elements of Wnt pathway. Here, Our researches showed that hepaCAM played a central role in modulating the Wnt/b-catenin signaling pathway by interfering nuclear protein levels of b-catenin, leading to down-regulate transcriptional activity of LEF/TCF and its target genes c-Myc and cyclinD1. Mechanistically, we demonstrated that hepaCAM-activated GSK3b led to elevate the phosphorylation of b-catenin, contributing to the aberrant translocation of b-catenin. In addition, Anti-proliferation and associated molecular mechanisms of hepaCAM were demonstrated by using vivo experiment. In conclusion, our reports uncover that expression of hepaCAM suppresses the proliferation of bladder cancer cells through a Wnt/b-catenin-dependent signaling pathway in vitro and in vivo.

Transient receptor potential (TRP) cation channels are essential for normal cellular physiology, and their abnormal expression may lead to a number of disorders, including podocytopathy. Therefore, it is crucial to understand the mechanisms underlying the regulation of TRP channels. In the present study, microRNA (miR)-135a was found to be upregulated in patients with focal segmental glomerulosclerosis and mice treated with adriamycin (ADR). In cultured podocytes, transforming growth factor (TGF)-β and ADR were found to promote miR-135a expression. Conversely, TRP channel 1 (TRPC1) protein levels were markedly downregulated in podocytes from mice treated with ADR, as well as in cultured podocytes treated with ADR and TGF-β. Ectopic expression of miR-135a led to severe podocyte injury and disarray of the podocyte cytoskeleton, whereas podocyte-specific expression of TRPC1 was able to reverse the pathological effects of miR-135a in cultured podocytes. Moreover, using Luciferase reporter assays and western blot analysis, TRPC1 was identified as a target gene of miR-135a. To the best of our knowledge, this is the first study to demonstrate the role of TRPC1 in the development of podocyte injury and disorders of the podocyte cytoskeleton, which may contribute to the development of novel therapeutics for podocyte injury-associated kidney diseases.

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Hepatocyte cell adhesion molecule (HepaCAM) plays a crucial role in tumor progression and has been recognized as a novel tumor suppressor gene. The high protein expression level of protein kinase Cε (PKCε) has been discovered in many tumor types. In the present study, we determined HepaCAM and PKCε protein levels in human clear cell renal cell carcinoma (ccRCC) tissues and analyzed the correlation between them. We observed an inverse relationship in the expression of HepaCAM and PKCε in ccRCC and adjacent normal tissues. In ccRCC tissue, HepaCAM expression was undetectable while PKCε expression was high; the opposite was found in the adjacent normal tissue. Western blot analysis demonstrated that PKCε cytosolic protein levels increased while plasma membrane protein levels decreased without any change in total protein following infection of the ccRCC cell line 786-0 with adenovirus-GFP-HepaCAM (Ad-GFP-HepaCAM). Moreover, the application of Ad-GFP-HepaCAM combined with a PKCε-specific translocation inhibitor (εV1-2) effectively inhibited 786-0 cell growth. Ad-mediated expression of HepaCAM in 786-0 cells reduced the levels of phosphorylated AKT and cyclin D1 and inhibited cell proliferation. In summary, our studies point to interesting connections between HepaCAM and PKCε in tissues and in vitro. HepaCAM may prevent the translocation of PKCε from cytosolic to particulate fractions, resulting in the inhibition of 786-0 cell proliferation. Therapeutic manipulation of these novel protein targets may provide new ways of treating ccRCC.

BackgroundDetection of ceftazidime/avibactam (CAZ/AVI) antibacterial activity is absolutely vital with the rapid growth of carbapenem resistant Enterobacteriaceae (CRE). But now, there is no available automated antimicrobial susceptibility testing card for CAZ/AVI, so Kirby-Bauer has become an economical and practical method for detecting CAZ/AVI antibacterial activity against Enterobacteriaceae.ResultIn this study, antimicrobial susceptibility testing of CAZ/AVI against 386 Enterobacteriaceae (188 Klebsiella pneumoniae, 122 Escherichia coli, 76 Enterobacter cloacae) isolated from clinical patients was performed by broth microdilution. Of the 386 strains, 54 extended spectrum β lactamases negative (ESBL(−)), 104 extended spectrum β lactamases positive (ESBL(+)), 228 CRE. 287 isolates were susceptible to CAZ/AVI and 99 isolates were resistant to CAZ/AVI. At the same time, to obtain optimal content avibactam (AVI) disk containing ceftazidime (30 μg), inhibition zone diameter of four kinds of ceftazidime (30 μg) disk containing different AVI content (0 μg, 10 μg, 25 μg, 50 μg) were tested by Kirby-Bauer method. The microdilution broth method interpretation was used as the standard to estimate susceptible or resistance and then coherence analysis was carried out between Kirby-Bauer and broth microdilution. The result shows the inhibition zone diameter of 30 μg/50 μg disk, susceptible isolates: 20.5 mm–31.5 mm, resistance isolates: 8.25 mm–21.5 mm. The inhibition zone diameter of 30 μg/25 μg disk, susceptible isolates: 19.7 mm–31.3 mm, resistance isolates: 6.5 mm–19.2 mm. The inhibition zone diameter of 30 μg/10 μg disk, susceptible isolates: 19.5 mm–31 mm, resistance isolates: 6.5 mm–11 mm. The inhibition zone diameter of ceftazidime (30 μg), susceptible isolates: 6.5 mm–27.5 mm, resistance isolates 6.5 mm.ConclusionOur results show that 30 μg/50 μg, 30 μg/25 μg, 30 μg/10 μg CAZ/AVI disk have significant statistical differences to determinate CAZ/AVI antibacterial activity, but for 30 μg/50 μg disk, there has a cross section between susceptible isolates (minimum 20.5 mm) and resistance isolates (maximum 21.5 mm). For 30 μg/25 μg disk, it is hard to distinguish the difference between susceptible isolates (minimum 19.7 mm) and resistance isolates (maximum 19.2 mm), so 30 μg/10 μg CAZ/AVI disk is more conducive to determinate antibacterial activity.