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Carbonic anhydrase 8 (CA8) is a member of the α‐carbonic anhydrase family but does not catalyze the reversible hydration of carbon dioxide. In the present study, we examined the effects of CA8 on two human colon cancer cell lines, SW480 and SW620, by suppressing CA8 expression through shRNA knockdown. Our results showed that knockdown of CA8 decreased cell growth and cell mobility in SW620 cells, but not in SW480 cells. In addition, downregulated CA8 resulted in a significant decrease of glucose uptake in both SW480 and SW620 cells. Interestingly, stable downregulation of CA8 decreased phosphofructokinase‐1 expression but increased glucose transporter 3 (GLUT3) levels in SW620 cells. However, transient downregulation of CA8 fails to up‐regulate GLUT3 expression, indicating that the increased GLUT3 observed in SW620‐shCA8 cells is a compensatory effect. In addition, the interaction between CA8 and GLUT3 was evidenced by pull‐down and IP assays. On the other hand, we showed that metformin, a first‐line drug for type II diabetes patients, significantly inhibited cell migration of SW620 cells, depending on the expressions of CA8 and focal adhesion kinase. Taken together, our data demonstrate that when compared to primary colon cancer SW480 cells, metastatic colon cancer SW620 cells respond differently to downregulated CA8, indicating that CA8 in more aggressive cancer cells may play a more important role in controlling cell survival and metformin response. CA8 may affect glucose metabolism‐ and cell invasion‐related molecules in colon cancer, suggesting that CA8 may be a potential target in future cancer therapy. Significance statement: This study demonstrates that when compared to primary colon cancer SW480 cells, metastatic colon cancer SW620 cells respond differently to downregulated CA8, indicating that CA8 in more aggressive cancer cells may play a more important role in controlling cell survival and metformin response. [ABSTRACT FROM AUTHOR]

Background: Soluble‐type hemojuvelin in serum and urine has been shown to be a biomarker in humans for chronic kidney disease (CKD) and acute kidney injury (AKI). No similar research has been conducted on cats. Objective: Urine hemojuvelin (u‐hemojuvelin) can be used as a clinical indicator for cats with various renal diseases. Animals Eighteen healthy cats, 10 cats with AKI, 21 cats with acute‐on‐chronic kidney injury (ACKI), and 45 cats with CKD were enrolled. Methods: The expression profile of u‐hemojuvelin was assessed by Western blot analysis, whereas the u‐hemojuvelin concentration was measured using an in‐house sandwich ELISA. Each cat's u‐hemojuvelin‐to‐creatinine ratio (UHCR) also was determined. Results: Significant differences were found in both u‐hemojuvelin concentration and UHCR between the control cats and the other cats (AKI, CKD, ACKI). Both u‐hemojuvelin and UHCR had high areas under the receiver operator curve (AUROC) for diagnoses of AKI (u‐hemojuvelin, 0.885; UHCR, 0.982), CKD (hemojuvelin, 0.869; UHCR, 0.959), and ACKI (hemojuvelin, 0.910; UHCR, 1). Late stage (International Renal Interest Society, IRIS stages 3 and 4) CKD cats had significantly higher u‐hemojuvelin concentration and UHCR than did early stage cats (IRIS stages 1 and 2). Both u‐hemojuvelin and UHCR were significantly correlated with high blood urea nitrogen, plasma creatinine, and plasma phosphate concentrations and with low hematocrit (Hct), red blood cell (RBC) count, and plasma albumin concentration. The UHCR values were also significantly correlated with white blood cell count in blood. Conclusion: Both u‐hemojuvelin and UHCR potentially can serve as diagnostic indicators for a range of renal diseases in cats. [ABSTRACT FROM AUTHOR]

Background: The risk of developing chronic kidney disease (CKD) among living kidney donors (LKDs) is seldom included in evaluations of patients' outcomes. Potential risk factors and new criteria for estimating the glomerular filtration rate (eGFR) indexed for body surface area (BSA) were investigated with a view to prevent the development of CKD in LKDs. Methods: We conducted a retrospective study of LKDs from May 1983 to March 2011. The Mann-Whitney U test and χ test were used to analyze the male versus female groups. Survival analysis was plotted as CKD-free survival and analyzed separately by different eGFR index classifications. The Cox regression model was used to identify potential risk factors for development of CKD. Results: A total of 105 LKDs with a mean age of 46.3 ± 12.5 years had a mean eGFR indexed for BSA of 88.9 ± 21.5 ml/min per 1.73 m. After a mean duration of 5.4 ± 4.9 years' follow-up, eGFR dropped to 61.4 ± 16.4 ml/min per 1.73 m ( p = 0.002). Median CKD-free survival was only 5.7 years. The difference between eGFR ≥ 80 ml/min per 1.73 m and <80 ml/min per 1.73 m was not statistically significant ( p = 0.980). Multivariate Cox regression analysis showed that higher eGFR at donation (HR = 0.952, p = 0.0199) could be a protective factor. The receiver operating characteristic (ROC) curve for initial eGFR with best sensitivity of 52.78 % and specificity of 81.40 % was obtained with a cutoff value of 90.2 ml/min per 1.73 m for preoperative eGFR. An eGFR of 90 ml/min per 1.73 m yielded a significant survival curve ( p = 0.0199) after 21 years of follow-up. Further classifications of eGFR >90 ml/min per 1.73 m into 90-99 ml/min per 1.73 m, 100-109 ml/min per 1.73 m, and ≥110 ml/min per 1.73 m were examined, but this survival curve was not statistically significant ( p = 0.1247). Conclusions: Living kidney donors will develop CKD after a long duration of follow-up if there is insufficiently high eGFR at donation. An eGFR above 90 ml/min per 1.73 m before donation is the only factor that predicts prevention of CKD. Larger studies with longer duration of follow-up are necessary to clarify the clinical outcome of this postoperative CKD group, especially for patients with eGFR between 80 and 90 ml/min per 1.73 m. [ABSTRACT FROM AUTHOR]