Doxorubicin (Dox)-induced cardiotoxicity has been a well‑known phenomenon to clinicians and scientists for decades. It has been confirmed that Dox‑dependent cardiotoxicity is accompanied by cardiac cellular senescence. However, the molecular mechanisms underlying Dox cardiotoxicity remains to be fully elucidated. Long non‑coding (lnc) RNAs regulate gene transcription and the fate of post‑transcriptional mRNA, which affects a broad range of age‑associated physiological and pathological conditions, including cardiovascular disease and cellular senescence. However, the functional role of lncRNAs in Dox‑induced cardiac cellular senescence remains largely unknown. Using the reverse transcription‑quantitative polymerase chain reaction method, the present study indicated that long intergenic non‑coding (linc) RNA‑p21 was highly expressed in Dox‑treated HL‑1 murine cardiomyocytes. Dox‑induced cardiac senescence was accompanied by decreased cellular proliferation and viability, increased expression of p53 and p16, and decreased telomere length and telomerase activity, while these effects were relieved by silencing endogenous lincRNA‑p21. We found that lincRNA‑p21 interacted with β‑catenin and that silencing β‑catenin abolished the anti‑senescent effect of lincRNA‑p21 silencing. It was observed that modulating lincRNA‑p21 to exert an anti‑senescent effect was dependent on decreasing oxidant stress. To conclude, the present findings suggest that lincRNA‑p21 may be involved in Dox‑associated cardiac cellular senescence and that silencing lincRNA‑p21 effectively protects against Dox cardiotoxicity by regulating the Wnt/β‑catenin signaling pathway and decreasing oxidant stress. Furthermore, modulating lincRNA‑p21 may have cardioprotective potential in patients with cancer receiving Dox treatment.

The AMPK-dependent induction of autophagy contributes to the neuroprotection of EPO on SCI.

Background. Thioredoxin-1 (Trx-1) is a small redox protein, which plays an important role in many biological processes. Although increased expression of Trx-1 in various solid tumors has been reported, the prognostic significance and function of Trx-1 in human gastric cancer (GC) are still unclear. Here, we investigated the clinical and prognostic significance of Trx-1 expression and the function and mechanism of Trx-1 in human GC. Methods. We analyzed Trx-1 mRNA expression from the GEO database and Trx-1 protein expression in 144 GC tissues using immunohistochemistry. Effects of Trx-1 on GC cell were assessed in vitro and in vivo through Trx-1 knockdown or overexpression. The antitumor effects of the Trx-1 inhibitor, PX-12, on GC cells were investigated. PTEN and p-AKT expressions were evaluated by Western blotting. Results. Increased Trx-1 expression was found in GC tissues and associated with poor prognosis and aggressive clinicopathological characteristics in patients with GC. High Trx-1 expression predicted poor prognosis, and its expression was an independent prognostic factor for overall survival of GC patients. Knockdown of Trx-1 expression inhibited GC cell growth, migration, and invasion in vitro and tumor growth and lung metastasis in vivo. Conversely, overexpression of Trx-1 promoted GC cell growth, migration, and invasion. We also found that PX-12 inhibited GC cell growth, migration, and invasion. Overexpression of Trx-1 caused a decrease in PTEN and increase in p-AKT levels whereas silencing Trx-1 caused an increase in PTEN and decrease in p-AKT levels in GC cells. Inhibition of AKT signaling pathway by MK2206 also inhibited GC cell growth, migration, and invasion. Conclusion. Our results indicate that Trx-1 may be a promising prognostic indicator and therapeutic target for GC patients.

Sarcopenia is an independent predictor of IAI. Our nomogram was a simple and practical instrument to quantify the individual risk of IAI and could be used to identify patients at a high risk.

The E3 ubiquitin protein UBR5 has been implicated in the regulation of multiple biological functions and has recently emerged as a key regulator of the ubiquitin-proteasome system (UPS) in cancer. However, the clinical significance and biological function of UBR5 in colorectal cancer (CRC) are poorly understood. In this study, we compared the expression pattern of UBR5 between CRC and adjacent normal tissues and found that UBR5 expression was frequently elevated in CRC, possibly through chromosomal gains. Using three CRC patient cohorts, we found that patients with high UBR5 mRNA levels, UBR5 gene amplification, or high nuclear UBR5 protein levels had poor prognoses. Multivariate analysis showed that the alterations in UBR5 were independent predictors of CRC prognosis with the TNM stage as a confounding factor. Furthermore, knockdown of UBR5 prevented the proliferation, colony formation, migration, and invasion of CRC cells in cell culture models. An in vivo animal model further confirmed that UBR5 knockdown reduced the growth of CRC tumors. In conclusion, our study is the first to systematically investigate the clinical and biological significance of UBR5 and to conclude that an elevated UBR5 level plays an oncogenic role and may be a potential prognostic marker in CRC.