Acute kidney injury (AKI) is a common clinical problem, and patients who survive AKI have a high risk of chronic kidney disease (CKD). The mechanism of CKD post‐AKI, characterized by progressive renal fibrosis, is still unclear. Maladaptive tubular epithelial cells (TECs) after AKI are considered a leading cause of renal fibrosis post‐AKI. TECs under maladaptive repair manifest characteristics of senescence. Removing senescent TECs by genetic ablation has been proven effective in reducing renal fibrosis. Senolytics, which eliminate senescent cells by pharmacological intervention, have been studied in a series of degenerative diseases. To our knowledge, the effects of senolytics on renal fibrosis post‐AKI have not been verified before. Here, we confirmed renal senescence in the unilateral ischemia/reperfusion injury murine model. Senescent TECs could activate fibroblasts and senolytics specifically induced apoptosis of senescent TECs. Next, we demonstrated that senolytics could reduce renal senescence and ameliorate renal fibrosis in both unilateral renal ischemia/reperfusion injury and multiple‐cisplatin‐treatment murine models. Our results indicate senescent TECs as a vital factor in renal fibrosis progression, and senolytic therapy might be promising for treating CKD post‐AKI.
Objectives: Our research investigated the relationship between childhood leukemia and breastfeeding in the P. R. of China.Methods: We conducted a retrospective case-control study from March 2008 to April 2017 at the Children’s Hospital of Zhejiang University, Zhejiang province, P. R. of China, which reviewed 958 children who had been diagnosed with leukemia in case group and 785 healthy children in control group. Data were obtained from medical records, and if the medical records were incomplete, we called mothers of children by phone to complete the data.Results: Breastfeeding reduces the risk of childhood leukemia; the effect is greater, if feeding continued for 7–9 months (p = 0.002). In addition, we suggest that some factors such as maternal age, smoking during pregnancy, abortion history, genetic factors, parents use of hair dye, and the history of using birth control pills before pregnancy can increase the risk of childhood leukemia.Conclusions: This study indicates that promoting breastfeeding for 7–9 months may help lower the childhood leukemia incidence. Our study firstly demonstrates that breastfeeding has protective effects against childhood leukemia in the P. R. of China.Abbreviations: ALL: Acute lymphocytic leukemia; AML: Acute myeloid leukemia
The transforming growth factor-β (TGF-β)/Smads signal plays an important role in cancer metastasis by mediating the epithelial-mesenchymal transition (EMT) in cancer cells. lnc-TSI is a recently identified long noncoding RNA that negatively regulates the TGF-β/Smads signal. The present study was conducted to test the hypothesis that lnc-TSI inhibits metastasis in clear cell renal cell carcinoma (ccRCC) by regulating the TGF-β/Smad3 pathway. Herein, we show that lnc-TSI was upregulated in ccRCC cells and tissue and was associated with activation of the TGF-β/Smads signal. Depleting lnc-TSI enhanced tumor cell invasion and metastasis
in vitro
and ccRCC lung metastasis
in vivo
, whereas overexpressing lnc-TSI inhibited ccRCC cell invasion and tumor metastasis. Mechanistic studies indicated that lnc-TSI specifically inhibited the phosphorylation of Smad3 and subsequent EMT by binding with the MH2 domain of Smad3 to block the interaction between Smad3 and TGF-β receptor I in ccRCC cells. In a cohort of 150 patients with ccRCC, expression of lnc-TSI in tumors was negatively correlated with phosphorylated (p)Smad3 and activated EMT markers. Patients with expression of tumor lnc-TSI greater than or equal to the median at radical nephrectomy had a higher survival rate compared to those with lnc-TSI below the median during follow-up. These findings reveal a new regulatory mechanism of ccRCC metastasis and suggest a potential molecular target for the development of anti-cancer drugs.
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