Targeting Nrf2 signaling pathways in the role of bladder cancer: From signal network to targeted therapy.

Bladder cancer (BC) is the most common malignancy of the urinary system and often recurs after tumor removal and/or is resistant to chemotherapy. In cancer cells, the activity of the signaling pathway changes significantly, affecting a wide range of cell activities from growth and proliferation to apoptosis, invasion and metastasis. Nrf2 is a transcription factor that plays an important role in cellular defense responses to a variety of cellular stresses. There is increasing evidence that Nrf2 acts as a tumor driver and that it is involved in the maintenance of malignant cell phenotypes. Abnormal expression of Nrf2 has been found to be common in a variety of tumors, including bladder cancer. Over-activation of Nrf2 can lead to DNA damage and the development of bladder cancer, and is also associated with various pathological phenomena of bladder cancer, such as metastasis, angiogenesis, and reduced toxicity and efficacy of therapeutic anticancer drugs to provide cell protection for cancer cells. However, the above process can be effectively inhibited or reversed by inhibiting Nrf2. Therefore, Nrf2 signaling may be a potential targeting pathway for bladder cancer. In this review, we will characterize this signaling pathway and summarize the effects of Nrf2 and crosstalk with other signaling pathways on bladder cancer progression. The focus will be on the impact of Nrf2 activation on bladder cancer progression and current therapeutic strategies aimed at blocking the effects of Nrf2. To better determine how to promote new chemotherapy agents, develop new therapeutic agents, and potential therapeutic targets.

[Impact of the freezing-thawing process on human sperm mitochondria].

OBJECTIVE: To study the structure and function of human sperm mitochondria before and after the freezing-thawing process. METHODS: Human sperm from healthy donors were subjected to the slow freezing-thawing process, and the sperm mitochondrion-related indexes compared before and after cryopreservation. The ultrastructural changes of the mitochondria were observed under the projection electron microscope, the mitochondrial membrane potential (MMP) and seminal adenosine triphosphate (ATP) content measured by immunofluorescence labeling and ELISA, respectively, and the sperm oxidative stress related indexes detected before and after sperm cryopreservation. RESULTS: Electron microscopy showed loose structures and widened crests of the sperm mitochondria, some with vacuole-like changes after the freezing-thawing process. The sperm after cryopreservation, compared with those before it, exhibited significantly increased contents of oxygen free radicals (ï¼»11.6 ± 3.8ï¼½% vs ï¼»9.6 ± 4.1ï¼½%, P < 0.05) and malondialdehyde (ï¼»3.2 ± 1.4ï¼½ vs ï¼»2.3 ± 1.2ï¼½ nmol/108, P < 0.05), but decreased antioxidant capacity (ï¼»0.6 ± 0.4ï¼½ vs ï¼»0.9 ± 0.4ï¼½ nmol/108, P < 0.05), superoxide dismutase activity (ï¼»0.9 ± 0.4ï¼½ vs ï¼»9.1 ± 3.9ï¼½ nmol/108, P < 0.05), MMP (ï¼»52.2 ± 6.2ï¼½% vs ï¼»55.7 ± 4.9ï¼½%, P = 0.026) and ATP production (ï¼»56.5 ± 9.0ï¼½ vs ï¼»61.3 ± 10.4ï¼½ pmol/106, P = 0.014). CONCLUSIONS: The freezing-thawing process can cause ultrastructural disorder of human sperm mitochondria, reduce their membrane potential and decrease their ATP production.