DRG2 Depletion Promotes Endothelial Cell Senescence and Vascular Endothelial Dysfunction.

Endothelial cell senescence is involved in endothelial dysfunction and vascular diseases. However, the detailed mechanisms of endothelial senescence are not fully understood. Here, we demonstrated that deficiency of developmentally regulated GTP-binding protein 2 (DRG2) induces senescence and dysfunction of endothelial cells. DRG2 knockout (KO) mice displayed reduced cerebral blood flow in the brain and lung blood vessel density. We also determined, by Matrigel plug assay, aorta ring assay, and in vitro tubule formation of primary lung endothelial cells, that deficiency in DRG2 reduced the angiogenic capability of endothelial cells. Endothelial cells from DRG2 KO mice showed a senescence phenotype with decreased cell growth and enhanced levels of p21 and phosphorylated p53, γH2AX, senescence-associated ß-galactosidase (SA-ß-gal) activity, and senescence-associated secretory phenotype (SASP) cytokines. DRG2 deficiency in endothelial cells upregulated arginase 2 (Arg2) and generation of reactive oxygen species. Induction of SA-ß-gal activity was prevented by the antioxidant N-acetyl cysteine in endothelial cells from DRG2 KO mice. In conclusion, our results suggest that DRG2 is a key regulator of endothelial senescence, and its downregulation is probably involved in vascular dysfunction and diseases.

A Sulfur-Infused Separator for Boosting Areal Capacity of Li-S Batteries.

This study presents a new approach for enabling the development of high-performance lithium-sulfur (Li-S) cells by simply inserting a sulfur-infused separator (SIS) between a common S cathode and a Li metal anode. All solid sulfur electrically isolated from the cathode is electrochemically reduced to polysulfides during the first discharge. Notably, scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM-EDS) studies have demonstrated that the S in the separator disappears completely even when the cell is discharged to 2.1 V in the first cycle. The combination of a SIS with a typical S cathode results in the doubling of the areal capacity with superior cycling stability upon comparison with the control cell. This result demonstrates that the introduction of additional active materials, such as elemental sulfur, to a separator is a highly effective method for the fabrication of Li-S cells with a high areal capacity.

Tristetraprolin posttranscriptionally downregulates PFKFB3 in cancer cells.

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases 3 (PFKFB3) catalyzes the first committed rate-limiting step of glycolysis and is upregulated in cancer cells. The mechanism of PFKFB3 expression upregulation in cancer cells has not been fully elucidated. The PFKFB3 3'-UTR is reported to contain AU-rich elements (AREs) that are important for regulating PFKFB3 mRNA stability. However, the mechanisms by which PFKFB3 mRNA stability is determined by its 3'-UTR are not well known. We demonstrated that tristetraprolin (TTP), an ARE-binding protein, has a critical function regulating PFKFB3 mRNA stability. Our results showed that PFKFB3 mRNA contains three AREs in the 3'-UTR. TTP bound to the 3rd ARE and enhanced the decay of PFKFB3 mRNA. Overexpression of TTP decreased PFKFB3 expression and ATP levels but increased GSH level in cancer cells. Overexpression of PFKFB3 cDNA without the 3'-UTR rescued ATP level and GSH level in TTP-overexpressing cells. Our results suggested that TTP post-transcriptionally downregulated PFKFB3 expression and that overexpression of TTP may contribute to suppression of glycolysis and energy production of cancer cells in part by downregulating PFKFB3 expression.

Percutaneous balloon compression of trigeminal ganglion for the treatment of idiopathic trigeminal neuralgia : experience in 50 patients.

OBJECTIVE: We assessed the surgical results of percutaneous balloon compression in 50 patients with idiopathic trigeminal neuralgia. METHODS: Fifty patients with follow-up period of more than 12 months were retrospectively analyzed. The mean follow-up period was 42 months (range, 12-82). The mean age was 65.8 years (range, 27-83). Seventeen patients (34%) had other previous surgical procedures. The balloon was inflated by injecting radio-contrast media under brief general anesthesia according to Mullan's technique. The mean inflating time was 88 seconds (range, 60-120). The whole procedure took about 20 minutes. RESULTS: We reported excellent and good results in 70% of the cases, poor in 6% as annoying dysesthesia, recurrence in 16%, and 8% failure due to technical deficiencies. Forty-six patients (92%) were initially relieved of their pain. There were permanent motor weakness of the masseter muscle in 4% of patients and transitory diplopia in 8%. Neither anesthesia dolorosa nor keratitis occurred. Almost all patients (92%) were discharged postoperatively within two days. CONCLUSION: These results indicate that balloon compression would be an effective method with acceptable morbidity, technically, it can be performed rapidly and simply in the treatment of idiopathic trigeminal neuralgia.