Nifedipine promotes the proliferation and migration of breast cancer cells

Nifedipine is widely used as a calcium channel blocker (CCB) to treat angina and hypertension,but it is controversial with respect the risk of stimulation of cancers. In this study, we demonstrated that nifedipine promoted the proliferation and migration of breast cancer cells both invivo and invitro. However, verapamil, another calcium channel blocker, didn’t exert the similar effects. Nifedipine and high concentration KCl failed to alter the [Ca2+]i in MDA-MB-231 cells, suggesting that such nifedipine effect was not related with calcium channel. Moreover, nifedipine decreased miRNA-524-5p, resulting in the up-regulation of brain protein I3 (BRI3). Erk pathway was consequently activated and led to the proliferation and migration of breast cancer cells. Silencing BRI3 reversed the promoting effect of nifedipine on the breast cancer. In a summary, nifedipine stimulated the proliferation and migration of breast cancer cells via the axis of miRNA-524-5p-BRI3–Erk pathway independently of its calcium channel-blocking activity. Our findings highlight that nifedipine but not verapamil is conducive for breast cancer growth and metastasis, urging that the caution should be taken in clinic to prescribe nifedipine to women who suffering both hypertension and breast cancer, and hypertension with a tendency in breast cancers

20-Hydroxyecdysone (20E) Primary Response Gene \u3cem\u3eE75\u3c/em\u3e Isoforms Mediate Steroidogenesis Autoregulation and Regulate Developmental Timing in \u3cem\u3eBombyx\u3c/em\u3e

The temporal control mechanisms that precisely control animal development remain largely elusive. The timing of major developmental transitions in insects, including molting and metamorphosis, is coordinated by the steroid hormone 20-hydroxyecdysone (20E). 20E involves feedback loops to maintain pulses of ecdysteroid biosynthesis leading to its upsurge, whereas the underpinning molecular mechanisms are not well understood. Using the silkworm Bombyx mori as a model, we demonstrated that E75, the 20E primary response gene, mediates a regulatory loop between ecdysteroid biosynthesis and 20E signaling. E75 isoforms A and C directly bind to retinoic acid receptor-related response elements in Halloween gene promoter regions to induce gene expression thus promoting ecdysteroid biosynthesis and developmental transition, whereas isoform B antagonizes the transcriptional activity of isoform A/C through physical interaction. As the expression of E75 isoforms is differentially induced by 20E, the E75-mediated regulatory loop represents a fine autoregulation of steroidogenesis, which contributes to the precise control of developmental timing

Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis.

Aberrant activation of NLRP3 inflammasome has an important function in the pathogenesis of various inflammatory diseases. Although many components and mediators of inflammasome activation have been identified, how NLRP3 inflammasome is regulated to prevent excessive inflammation is unclear. Here we show NLRP3 inflammasome stimulators trigger Src homology-2 domain containing protein tyrosine phosphatase-2 (SHP2) translocation to the mitochondria, to interact with and dephosphorylate adenine nucleotide translocase 1 (ANT1), a central molecule controlling mitochondrial permeability transition. This mechanism prevents collapse of mitochondrial membrane potential and the subsequent release of mitochondrial DNA and reactive oxygen species, thus preventing hyperactivation of NLRP3 inflammasome. Ablation or inhibition of SHP2 in macrophages causes intensified NLRP3 activation, overproduction of proinflammatory cytokines IL-1β and IL-18, and increased sensitivity to peritonitis. Collectively, our data highlight that, by inhibiting ANT1 and mitochondrial dysfunction, SHP2 orchestrates an intrinsic regulatory loop to limit excessive NLRP3 inflammasome activation

Outreach syphilis testing services by different health providers to female sex workers in southern China.

Health providers have played important roles on delivering prevention and care services to control syphilis in China. The current study was aimed to evaluate the performance of different health providers in providing outreach syphilis testing services to female sex workers (FSWs). The current study carried out during April to August 2009 in Liuzhou was aimed to investigate the services delivered by two different types of clinics in China. A total of 1,808 FSWs recruited from sex work venues were included in the study. Prevalence of positive syphilis test (6.4%) among FSWs accessed by the local center for disease control outreach teams (CDC teams) was significantly lower than that (9.3%) among FSWs accessed by the local reproductive health hospital outreach teams (RHH teams). As compared with CDC teams, RHH teams had more FSWs to be successfully referred to the designated STD clinics for further syphilis confirmation and intervention (85.7% vs. 26.7%, P<0.001). These findings indicate that RHH teams may be more efficient than CDC teams to provide outreach-based services to FSWs. Participation of the reproductive health providers or other medical facilities in outreach services to FSWs should be considered in developing intervention programs in China

Scaling of pressure-induced and doping-induced superconductivity in the Ca10(PtnAs8)(Fe2As2)5 arsenides

The Ca10(PtnAs8)(Fe2As2)5 (n=3,4) compounds are a new type of iron pnictide superconductor whose structures consist of stacking Ca-PtnAs8-Ca-Fe2As2 layers in a unit cell. When n=3 (the 10-3-8 phase), the undoped compound is an antiferromagnetic (AFM) semiconductor, while, when n=4 (the 10-4-8 phase), the undoped compound is a superconductor (Tc=26K), a difference that has been attributed to the electronic character of the PtnAs8 intermediary layers. Here we report high-pressure studies on 10-3-8 and 10-4-8, using a combination of in-situ resistance, magnetic susceptibility, Hall coefficient and X-ray diffraction measurements. We find that the AFM order in undoped 10-3-8 is suppressed completely at 3.5 GPa and that superconductivity then appears in the 3.5-7 GPa pressure range with a classic dome-like behavior. In contrast, Tc in the 10-4-8 phase displays a monotonic decrease with increasing pressure. Our results allow for the establishment of a unique correspondence between pressure-induced and doping-induced superconductivity in the high-Tc iron pnictides, and also points the way to an effective strategy for finding new high-Tc superconductors.Comment: 25 pages, 5 figure