Ginsenoside-Rg1 mediates a hypoxia-independent upregulation of hypoxia-inducible factor-1α to promote angiogenesis

Hypoxia-inducible factor (HIF-1) is the key transcription regulator for multiple angiogenic factors and is an appealing target. Ginsenoside-Rg1, a nontoxic saponin isolated from the rhizome of Panax ginseng, exhibits potent proangiogenic activity and has the potential to be developed as a new angiotherapeutic agent. However, the mechanisms by which Rg1 promotes angiogenesis are not fully understood. Here, we show that Rg1 is an effective stimulator of HIF-1α under normal cellular oxygen conditions in human umbilical vein endothelial cells. HIF-1α steady-state mRNA was not affected by Rg1. Rather, HIF-1α protein synthesis was stimulated by Rg1. This effect was associated with constitutive activation of phosphatidylinositol 3-kinase (PI3K)/Akt and its effector p70 S6 kinase (p70S6K), but not extracellular-signal regulated kinase 1/2. We further revealed that HIF-1α induction triggered the expression of target genes, including vascular endothelial growth factor (VEGF). The use of small molecule inhibitors LY294002 or rapamycin to inhibit PI3K/Akt and p70S6K activities, respectively, resulted in diminished HIF-1α activation and subsequent VEGF expression. RNA interference-mediated knockdown of HIF-1α suppressed Rg1-induced VEGF synthesis and angiogenic tube formation, confirming that the effect was HIF-1α specific. Similarly, the angiogenic phenotype could be reversed by inhibition of PI3K/Akt and p70S6K. These results define a hypoxia-independent activation of HIF-1α, uncovering a novel mechanism for Rg1 that could play a major role in angiogenesis and vascular remodeling

Imaging in assessing hepatic and peritoneal metastases of gastric cancer: a systematic review

<p>Abstract</p> <p>Background</p> <p>Hepatic and peritoneal metastases of gastric cancer are operation contraindications. Systematic review to provide an overview of imaging in predicting the status of liver and peritoneum pre-therapeuticly is essential.</p> <p>Methods</p> <p>A systematic review of relevant literatures was performed in Pubmed/Medline, Embase, The Cochrane Library and the China Biological Medicine Databases. QUADAS was used for assessing the methodological quality of included studies and the bivariate model was used for this meta-analysis.</p> <p>Results</p> <p>Totally 33 studies were included (8 US studies, 5 EUS studies, 22 CT studies, 2 MRI studies and 5 18F-FDG PET studies) and the methodological quality of included studies was moderate. The result of meta-analysis showed that CT is the most sensitive imaging method [0.74 (95% CI: 0.59-0.85)] with a high rate of specificity [0.99 (95% CI: 0.97-1.00)] in detecting hepatic metastasis, and EUS is the most sensitive imaging modality [0.34 (95% CI: 0.10-0.69) ] with a specificity of 0.96 (95% CI: 0.87-0.99) in detecting peritoneal metastasis. Only two eligible MRI studies were identified and the data were not combined. The two studies found that MRI had both high sensitivity and specificity in detecting liver metastasis.</p> <p>Conclusion</p> <p>US, EUS, CT and ¹⁸F-FDG PET did not obtain consistently high sensitivity and specificity in assessing liver and peritoneal metastases of gastric cancer. The value of laparoscopy, PET/CT, DW-MRI, and new PET tracers such as ¹⁸F-FLT needs to be studied in future.</p

Genome Sequence and Transcriptome Analysis of the Radioresistant Bacterium Deinococcus gobiensis: Insights into the Extreme Environmental Adaptations

The desert is an excellent model for studying evolution under extreme environments. We present here the complete genome and ultraviolet (UV) radiation-induced transcriptome of Deinococcus gobiensis I-0, which was isolated from the cold Gobi desert and shows higher tolerance to gamma radiation and UV light than all other known microorganisms. Nearly half of the genes in the genome encode proteins of unknown function, suggesting that the extreme resistance phenotype may be attributed to unknown genes and pathways. D. gobiensis also contains a surprisingly large number of horizontally acquired genes and predicted mobile elements of different classes, which is indicative of adaptation to extreme environments through genomic plasticity. High-resolution RNA-Seq transcriptome analyses indicated that 30 regulatory proteins, including several well-known regulators and uncharacterized protein kinases, and 13 noncoding RNAs were induced immediately after UV irradiation. Particularly interesting is the UV irradiation induction of the phrB and recB genes involved in photoreactivation and recombinational repair, respectively. These proteins likely include key players in the immediate global transcriptional response to UV irradiation. Our results help to explain the exceptional ability of D. gobiensis to withstand environmental extremes of the Gobi desert, and highlight the metabolic features of this organism that have biotechnological potential

Clinical research evidence of cupping therapy in China: a systematic literature review

<p>Abstract</p> <p>Background</p> <p>Though cupping therapy has been used in China for thousands of years, there has been no systematic summary of clinical research on it.</p> <p>This review is to evaluate the therapeutic effect of cupping therapy using evidence-based approach based on all available clinical studies.</p> <p>Methods</p> <p>We included all clinical studies on cupping therapy for all kinds of diseases. We searched six electronic databases, all searches ended in December 2008. We extracted data on the type of cupping and type of diseases treated.</p> <p>Results</p> <p>550 clinical studies were identified published between 1959 and 2008, including 73 randomized controlled trials (RCTs), 22 clinical controlled trials, 373 case series, and 82 case reports. Number of RCTs obviously increased during past decades, but the quality of the RCTs was generally poor according to the risk of bias of the Cochrane standard for important outcome within each trials. The diseases in which cupping was commonly employed included pain conditions, herpes zoster, cough or asthma, etc. Wet cupping was used in majority studies, followed by retained cupping, moving cupping, medicinal cupping, etc. 38 studies used combination of two types of cupping therapies. No serious adverse effects were reported in the studies.</p> <p>Conclusions</p> <p>According to the above results, quality and quantity of RCTs on cupping therapy appears to be improved during the past 50 years in China, and majority of studies show potential benefit on pain conditions, herpes zoster and other diseases. However, further rigorous designed trials in relevant conditions are warranted to support their use in practice.</p

Ruthenium benzylidene and vinylidene complexes in a sulfur-rich coordination environment

Interaction of Ru(=CHPh)(PCy3)2Cl2 (Cy = cyclohexyl) with K[N(PPh2S)2] affords air-stable Ru(=CHPh)[N(PPh2S)2]2, 1, which has been characterized by X-ray diffraction. The Ru-Cα and average Ru-S distance for 1 are 1.88(2) and 2.377 Å, respectively. Reaction of 1 with CO gives sis-Ru(CO)2[N(PPh2S)2]2. Complex 1 undergoes metathesis with ethyl vinyl ether to give the methoxycarbene complex Ru(=CHOEt)[N(PPh2S)2]2, 3. Treatment of Ru(=CHPh)-(PCy3)2Cl2 with K[N(PPh2Se)2] affords Ru(=CHPh)[PPh2NP(Se)Ph2]2, 4, which has been characterized by X-ray crystallography. The Ru-C, average Ru-P, and average Ru-Se distances are 1.873(8), 2.383, and 2.450 Å, respectively. Reactions of Ru(=CHPh)(PCy3)2Cl2 with K[P(OR)2S2] afford cis-Ru(=CHPh)(PCy3)[P(OR)2S2]2 (R = Et (6) and i-Pr (7)). Reaction of Ru(=CHPh)(PCy3)2Cl2 with 1,4,7-trithiacyclononane ([9]aneS3) gives [([9]aneS3)Ru-(=CHPh)(PCy3)Cl]Cl, 8. Treatment of Ru(=C=CHPh)(PCy3)2Cl2 with K[N(PPh2S)2] or [9]aneS3 affords cis-Ru(=C=CHPh)(PCy3)[N(PPh2S)2]2 (9) or ([9]aneS3)Ru(PCy3)Cl2 (10), respectively. The Ru-C, Ru-P, and average Ru-S distances in 9 are 1.80(1), 2.420(3), and 2.479 Å, respectively. Complexes 1 and 8 are active catalysts for ring-opening metathesis polymerization of norbornene.link_to_subscribed_fulltex