Autophagy related 4B, upregulated by HIF-1α, attenuates the sensitivity to cisplatin in nasopharyngeal carcinoma cells.

OBJECTIVE: Increasing evidence has shown that autophagy related proteins and hypoxia-inducible factor-1α (HIF-1α) are both involved in the malignant progress of nasopharyngeal carcinoma (NPC), and HIF-1α plays an emerging role in the chemosensitivity of NPC cells. However, it is still unknown whether autophagy related proteins are associated with HIF-1α in regulating the chemosensitivity of NPC cells. MATERIALS AND METHODS: Quantitative Real-time PCR (qPCR) was applied to determine mRNA levels of HIF-1α and the autophagy related proteins, such as ATG3, ATG4B, ATG5, Beclin1, ATG7, ATG10, ATG12 and ATG16L1. Western blot was applied to determine protein levels of HIF-1α, ATG4B and cleaved Caspase-3. Cell viability and death were investigated by cell counting kit-8 and trypan blue exclusion assay. In addition, Caspase-3 activity was detected to reflect apoptosis. Furthermore, Luciferase reporter assay was applied to explore the mechanism by which HIF-1α transcriptionally upregulated ATG4B expression. RESULTS: Our study reveals that HIF-1α increased ATG4B expression in NPC cells, and in turn upregulated the cisplatin (DDP)-induced protective autophagy, resulting in enhanced killing effect of DDP to NPC cells. In mechanism, reporter assay showed that HIF-1α upregulated ATG4B expression by activating its gene promoter region. The binding site (-225 to -216) was required for HIF-1α-induced increase of ATG4B gene promoter activity. CONCLUSIONS: These results indicate that HIF-1α elevates ATG4B via promoting its transcription, which alleviates the sensitivity of DDP in NPC cells through enhancing protective autophagy, suggesting that ATG4B, upregulated by HIF-1α, may be a novel target for DDP sensitization in the treatment of NPC in clinic.

Anterior-posterior and rotational displacement of the tibia elicited by quadriceps contraction.

The anterior-posterior displacement and rotation of the tibia elicited by isolated loading of the quadriceps muscle was determined as a function of joint angle and muscle load using a computerized radiographic technique. Data collected from 12 fresh-frozen cadaveric knees demonstrated that quadriceps contraction can result in significant (less than 7 mm) anterior displacement of the tibia in the range of 0 degrees to 80 degrees of flexion, and a mild (less than 2 mm) posterior displacement in the range of 80 degrees to 120 degrees of flexion. Peak anterior displacement of 6.3 mm was observed at 30 degrees of flexion under a 12 kg load in the quadriceps, while a constant 1.5 mm posterior displacement was observed throughout flexion angles exceeding 80 degrees. It was further shown that the magnitude of the anterior displacement increased nonlinearly as the quadriceps force increased. Loading of the quadriceps also resulted in internal rotation of the tibia in the range of 0 degrees to 90 degrees of flexion, and in external rotation of the tibia in the range of 90 degrees to 120 degrees. Peak internal rotation of 7 degrees was observed at 15 degrees of flexion and a peak external rotation of 1 degrees was detected at 120 degrees of flexion. Larger quadriceps load resulted in larger rotation. We concluded that quadriceps contraction during knee extension has direct impact on anterior displacement and rotation of the tibia and therefore on anterior cruciate ligament stress, increasing it as the muscle's force is increased during knee extension.(ABSTRACT TRUNCATED AT 250 WORDS)

Hair chromium levels in patients with vascular diseases.

The chromium levels in the hair of patients with hyperlipemia and coronary heart disease were found to be similar to those of healthy controls (p greater than 0.2). In patients with cerebral hemorrhage and cerebral thrombosis, significantly higher hair chromium values were observed than in healthy subjects (p less than 0.001). The possible significance of these findings is discussed.