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Transient receptor potential melastatin 7 (TRPM7) functions as a Mg2+/Ca2+-permeable channel fused with a kinase domain and regulates various physical processes and diseases. However, its effects on pathogenesis of human bladder cancer (BCa) has not been clarified yet. Our microarray analysis has suggested that calcium signaling pathway is connected with bladder cancer via MAPK pathway. Therefore, we aim to investigate the mechanism of TRPM7 in BCa tumorigenesis by using BCa tissues compared with normal bladder epithelium tissues, as well as using distinct BCa cell lines (EJ, 5637 and T24). We observed increased TRPM7 expression and dysregulation of proteins involved in Epithelial-Mesenchymal Transition (EMT) in BCa tissues. Moreover, knockdown of TRPM7 in BCa cells reversed the EMT status, accompanied by increase of reactive oxygen species (ROS). Furthermore, TRPM7 deficiency could inhibit BCa cell proliferation, migration and invasion, as well as induce p-ERK1/2 and suppress PI3K/AKT at the protein level. Downregulation of TRPM7 promoted cell cycle arrest at G0/G1 phase and apoptosis in vitro, which could be recovered by pre-treatment with U0126 to deactivate ERK1/2, suggesting a close correlation between TRPM7 and the MAPK signaling pathway. Furthermore, a NOD/SCID mouse model transplanted using the BCa cells was established, revealing delayed tumor growth by reduced protein activity and mRNA transcription of TRPM7 in vivo. Our results suggested TRPM7 might be essential for BCa tumorigenesis by interfering BCa cell proliferation, motility and apoptosis.

Actin polymerizes and forms filamentous structures (F-actin) in the cytoplasm of eukaryotic cells. It also exists in the nucleus and regulates various nucleic acid transactions, particularly through its incorporation into multiple chromatin-remodeling complexes. However, the specific structure of actin and the mechanisms that regulate its polymeric nature inside the nucleus remain unknown. Here, we report the crystal structure of nuclear actin (N-actin) complexed with actin-related protein 4 (Arp4) and the helicase-SANT-associated (HSA) domain of the chromatin remodeler Swr1. The inner face and barbed end of N-actin are sequestered by interactions with Arp4 and the HSA domain, respectively, which prevents N-actin from polymerization and binding to many actin regulators. The two major domains of N-actin are more twisted than those of globular actin (G-actin), and its nucleotide-binding pocket is occluded, freeing N-actin from binding to and regulation by ATP. These findings revealed the salient structural features of N-actin that distinguish it from its cytoplasmic counterpart and provide a rational basis for its functions and regulation inside the nucleus.nuclear actin | Arp4 | chromatin remodeling | crystal structure

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Quercetin is an important dietary flavonoid present in fruits and vegetables and has attracted attention because of its anti-inflammatory and anti-oxidative properties. Inflammation and oxidative stress play important roles in posttraumatic cardiomyocyte apoptosis, which contributes to secondary cardiac dysfunction. This study investigates the protective effect of quercetin on trauma-induced secondary cardiac injury and the mechanisms involved. Widely accepted nonlethal mechanical trauma models were established. In vivo, cardiomyocyte apoptosis and cardiac dysfunction in rats were assessed using TUNEL staining and a biological mechanic experiment system. In vitro, cell viability, tumour necrosis factor-α (TNF-α), reactive oxygen species (ROS) and [Ca2+]i of H9c2 cells were detected using an MTT assay, ELISA, and 2′,7′-dichlorofluorescin diacetate and fluo-4 acetoxymethyl ester assays respectively. Quercetin pretreatment (20 mg/kg i.p.; 0.5 h before trauma) significantly improved posttraumatic cardiomyocyte apoptosis and cardiac dysfunction. Pretreatment with quercetin (20 μM; 24 h before trauma plasma addition) significantly attenuated trauma-induced viability decreases, TNF-α increases, ROS overproduction and [Ca2+]i overload in H9c2 cells. In conclusion, quercetin may reverse posttraumatic cardiac dysfunction by reducing cardiomyocyte apoptosis through the suppression of TNF-α increases, ROS overproduction and Ca2+ overload in cardiomyocytes, representing a potential preventive approach for the treatment of secondary cardiac injury after mechanical trauma.

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Previous studies examining the association between job stress and blood lipids have produced mixed findings. We sought to investigate the association between job stress and blood lipids among Chinese workers. Methods: A total of 544 subjects (367 men and 177 women) without known diseases from the Stress and Health in Shenzhen Workers (SHISO) cross-sectional study were analyzed. Job stress was evaluated by the effort-reward imbalance (ERI) model. The associations between job stress and blood lipids, such as for total cholesterol (TCHO), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), were explored by multiple linear regression. The association between job stress and combined dyslipidemia was examined by multiple logistic regression. Results: Compared with their corresponding low level groups, groups with high levels of effort, overcommitment and ERI had a significantly increased risk of combined dyslipidemia with adjusted odd ratios (ORs) of 3.5 (95% CI 1.8-6.7), 4.2 (95% CI 2.3-7.7) and 2.7 (95% CI 1.5-5.1), respectively, whereas high rewards significantly reduced the risk of combined dyslipidemia (adjusted OR 0.3, 95% CI 0.2-0.6) compared with low rewards. Effort, overcommitment and ERI were significantly positively related to TG and LDL-C, while rewards were inversely related to them. No significant associations were observed between job stress and TCHO and HDL-C. The results were similar for men and women. Conclusions: Effort, overcommitment, low reward and ERI increased the risk of dyslipidemia among Chinese workers, and they were significantly associated with TG and LDL-C rather than TCHO or HDL-C. Increasing blood lipids may be the possible link between job stress and coronary heart disease. (J Occup Health 2011; 53: 334-342)

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