Autophagy is activated to protect against podocyte injury in adriamycin-induced nephropathy.

Podocytes are highly differentiated epithelial cells wrapping glomerular capillaries to form the filtration barrier in kidneys. As such, podocyte injury or dysfunction is a critical pathogenic event in glomerular disease. Autophagy plays an important role in the maintenance of the homeostasis and function of podocytes. However, it is less clear whether and how autophagy contributes to podocyte injury in glomerular disease. Here, we have examined the role of autophagy in adriamycin-induced nephropathy, a classic model of glomerular disease. We show that autophagy was induced by adriamycin in cultured podocytes in vitro and in podocytes in mice. In cultured podocytes, activation of autophagy with rapamycin led to the suppression of adriamycin-induced apoptosis, whereas inhibition of autophagy with chloroquine enhanced podocyte apoptosis during adriamycin treatment. To determine the role of autophagy in vivo, we established an inducible podocyte-specific autophagy-related gene 7 knockout mouse model (Podo-Atg7-KO). Compared with wild-type littermates, Podo-Atg7-KO mice showed higher levels of podocyte injury, glomerulopathy, and proteinuria during adriamycin treatment. Together, these observations support an important role of autophagy in protecting podocytes under the pathological conditions of glomerular disease, suggesting the therapeutic potential of autophagy induction.

AKI on CKD: heightened injury, suppressed repair, and the underlying mechanisms.

Acute kidney injury (AKI) and chronic kidney disease (CKD) are interconnected. Although AKI-to-CKD transition has been intensively studied, the information of AKI on CKD is very limited. Nonetheless, AKI, when occurring in patients with CKD, is known to be more severe and difficult to recover. CKD is associated with significant changes in cell signaling in kidney tissues, including the activation of transforming growth factor-ß, p53, hypoxia-inducible factor, and major developmental pathways. At the cellular level, CKD is characterized by mitochondrial dysfunction, oxidative stress, and aberrant autophagy. At the tissue level, CKD is characterized by chronic inflammation and vascular dysfunction. These pathologic changes may contribute to the heightened sensitivity of, and nonrecovery from, AKI in patients with CKD.

The association of pretreatment thrombocytosis with prognosis and clinicopathological significance in cervical cancer: a systematic review and meta-analysis.

Previous studies reported inconsistent findings about the relationship between pretreatment thrombocytosis and survival in patients with cervical cancer. This study aimed to evaluate the prognostic significance of thrombocytosis in cervical cancer. We searched databases to identify relevant articles. Pooled hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Fourteen studies including 3,394 patients were eligible for the meta-analysis. Overall, an elevated platelet count was significantly associated with inferior overall survival (OS, hazard ratio [HR]: 1.66, 95% confidence interval [CI]: 1.42-1.95, P < 0.001) and recurrence-free survival (RFS, HR: 1.67, 95% CI: 1.15-2.42, P = 0.007) but not progression-free survival (PFS, HR: 1.21, 95% CI: 0.89-1.64; P = 0.235). The results were similar for low stage patients treated with surgery alone. Moreover, a pretreatment thrombocytosis status was significantly associated with higher clinical stage (odd ratio [OR]: 2.39, 95% CI: 1.68-3.38, P < 0.001), positive pelvic node status (OR: 1.58, 95% CI: 1.01- 2.45, P = 0.044) and larger tumor size (OR: 2.32, 95% CI: 1.39-3.87, P = 0.001). Pretreatment thrombocytosis is an independent prognosis predictor in cervical cancer patients. It may be used as a readily available biomarker to refine clinical outcome prediction for cervical cancer patients.