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Background: The dysregulation of circular RNAs (circRNAs) has been identified in various human diseases, including osteoarthritis (OA). The purpose of this study was to identify the role and mechanism of circ_SLC39A8 in regulating the progression of OA., Methods: The expression levels of circ_SLC39A8, miR-591, and its potential target gene, interleukin-1-receptor-associated kinase 3 (IRAK3), were identified by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were determined by Cell Counting Kit-8 (CCK-8) assay and flow cytometry, respectively. The relationship between miR-591 and circ_SLC39A8 or IRAK3 was predicted by bioinformatics tools and verified by dual-luciferase reporter., Results: Circ_SLC39A8 and IRAK3 were upregulated and miR-591 was downregulated in OA cartilage tissues. Knockdown of circ_SLC39A8 inhibited apoptosis and inflammation in OA chondrocytes, while these effects were reversed by downregulating miR-591. Promotion cell viability effects of miR-591 were partially reversed by IRAK3 overexpression., Conclusion: Our findings indicated that knockdown of circ_SLC39A8 delayed the progression of OA via modulating the miR-591-IRAK3 axis, providing new insight into the molecular mechanisms of OA pathogenesis.

Glypican-3 (GPC3) is a diagnostic biomarker for hepatocellular carcinoma (HCC). Although numerous designs targeting GPC3 have been reported, the HCC diagnostic agents with specific tumor accumulation and low background, particularly in normal liver tissue, are still in need. Peptides have attracted considerable attention as an imaging probe due to their low immunogenicity, short in vivo circulation time, and acceptable production cost. Herein, a two-step phage display screening approach was performed against GPC3-high expression tumor xenografts in vivo, followed by human recombinant GPC3 protein in vitro. A GPC3-specific binding peptide, named TJ12P2, with the sequence of Ser-Asn-Asp-Arg-Pro-Pro-Asn-Ile-Leu-Gln-Lys-Arg (SNDRPPNILQKR) was identified. The apparent Kd value between TJ12P2 and the GPC3 protein was measured as 158.2 ± 26.25 nM. After 18F labeling, 18F-AlF-NOTA-TJ12P2 was found accumulated in the tumors by positron emission tomography (PET) imaging in two HCC subcutaneous tumor models (HepG2 and SMMC-7721) with high GPC3 expression. Static PET imaging revealed that 18F-AlF-NOTA-TJ12P2 accumulation in the HepG2 and SMMC-7721 tumors reached 1.825 ± 0.296 %ID g-1 and 1.575 ± 0.520 %ID g-1, with tumor-to-muscle ratios of 4.14 ± 0.50 and 4.25 ± 0.25, respectively, at 30 min post-injection (p.i.). Much less accumulation (0.533 ± 0.078 %ID g-1) of the 18F-AlF-NOTA-TJ12P2 was found in the control PC3 tumors with low GPC3 expression. More importantly, no obvious normal liver uptake of TJ12P2 was observed in the abovementioned animal models. As a result, a novel peptide targeting GPC3, TJ12P2, with strong affinity and specificity was identified using a two-step phage display screening technique in the present study. The 18F-AlF-NOTA-TJ12P2 may be a promising PET imaging probe with translational potential for accurate HCC diagnosis.

Background: Researchers have developed several equations to predict glomerular filtration rate (GFR) in patients with chronic kidney diseases (CKD). However, there are scarcely any studies performed to discern the best equation to estimate GFR in patients with pure obstructive nephropathy. In present study, we assessed the suitability of six prediction equations and compared their performance in eGFR evaluation for Chinese patients with obstructive nephropathy., Methods: A total of 245 adult patients with obstructive nephropathy were enrolled. We evaluated the performance of the 3 Modification of Diet in Renal Disease equations (MDRD) (the original MDRD7, 7MDRD; the abbreviated MDRD, aMDRD; and re-expressed abbreviated MDRD, re-aMDRD) and 3 Chronic Kidney Disease Epidemiology Collaboration equations (CKD-EPI) (CKD-EPI equation based on creatinine alone, CKD-EPIcr; CKD-EPI equation based on cystatin C alone, CKD-EPIcys; CKD-EPI equation based on combined creatinine-cystatin, CKD-EPIcr-cys). The measured GFR (mGFR) by 99 mTc-DTPA renal dynamic imaging method was used as the reference GFR., Results: The mean age of the study population was 51.61 ± 14.17 and 131 were male (53.47 %). The mean measured GFR was 66.54 ± 23.99 ml/min/1.73 m 2 . Overall, the CKD-EPIcr-cys equation gave the best performance with the best correlation (R = 0.72) and agreement (-34.87, 40.83). CKD-EPIcr-cys equation also exhibited the highest accuracy (69.39 %, P < 0.01) and diagnostic efficacy (ROC AUC  = 0.874) with the smallest bias (2.98, P < 0.01). In the subgroup of the lowest GFR, CKD-EPIcys equation exhibited the highest accuracy (52.69 %) and the smallest bias (0.27). In the youngest age subgroup, CKD-EPIcys equation had the highest accuracy (71.64 %) and the smallest bias (-1.24). In other subgroups stratified by GFR, age and gender, CKD-EPIcr-cys equation remained the best performance., Conclusion: The 3 CKD-EPI equations performed better than the 3 MDRD equations in estimating GFR in Chinese obstructive nephropathy patients; while the CKD-EPI equation based on combined creatinine-cystatin C provided the best estimation of GFR.

Glypican-3 (GPC3) is a key member of the glypican family that is expressed on the cell surface by a glycosyl-phosphatidyl-inositol (GPI) anchor. It plays a significant role in hepatocellular carcinoma (HCC) development, angiogenesis, and metastasis. Most HCC overexpress GPC3, whereas little GPC3 can be detected in normal adult liver and benign liver lesions. Therefore, it is important to understand the function of GPC3 in HCC tumor development as the GPC3 ligand may facilitate detection of HCC. In this study, a 12-mer peptide with the sequence of DHLASLWWGTEL (denoted as TJ12P1) was identified by screening a phage display peptide library that demonstrated ideal GPC3 binding affinity. We used TJ12P1 conjugated with near-infrared fluorescent (NIFR) dye Cy5.5 for tumor imaging. After intravenous injection of the imaging agent, TJ12P1, xenografts of high GPC3 expressing hepatocellular carcinoma cell line, HepG2, demonstrated significantly higher tumor accumulation (tumor/muscle ratio: 3.98 ± 0.36) than those of low GPC3 expressing prostate cancer cell line, PC3 (tumor/muscle ratio: 2.03 ± 0.23). More importantly, GPC3 expression in tumor samples of patients could be visualized using TJ12P1, suggesting the potential use of this peptide as a probe for HCC detection. Our study has successfully identified a promising GPC3-binding peptide ligand for detecting the GPC3 expression in HCC not only in vitro but also in vivo by its noninvasive imaging.