Activity

For lung adenocarcinoma, arm aneuploidy landscape among primary and metastatic sites, and among different driver and frequently mutated gene groups have not been previously studied. We collected the largest cohort of LUAD patients (n=3533) to date and analyzed the profiles of chromosome arm aneuploidy (CAA), and its association with different metastatic sites and mutated gene groups. Our results showed distant metastasis (bone, brain, liver) were characterized by high CAA burden and biased towards arm losses compared to regional metastasis (pleura, chest) and primary tumors. Moreover, EGFR, MET, PIK3CA, PKHD1 and RB1 mutant groups were found to have high CAA burden, while those with BRAF, ERBB2 and KRAS mutations belonged to the low CAA burden group. Comparing EGFR L858R and EGFR 19del mutants, distinct CAA co-occurrences were observed. Network-based stratification with population based genomic evolution analysis revealed two distinct subtypes of LUAD with different CAA signatures and unique CAA order of acquisition. In summary, our study presented a comprehensive characterization of arm aneuploidy landscape and evolutionary trajectories in lung adenocarcinoma, which could provide basis for both biological and clinical investigations in the future.Ischemic stroke is one of the leading causes of death and disability among adults. Despite the economic burden of the disease, available treatment options are still very limited. With the exception of anti-thrombolytics and hypothermia, current therapies fail to reduce neuronal injury, neurological deficits and mortality rates, suggesting that the development of novel and more effective therapies against ischemic stroke is urgent. In the present study, we found that artemether, which has been used in the clinic as an anti-malarial drug, was able to improve the neurological deficits, attenuate the infarction volume and the brain water content in a middle cerebral artery occlusion (MCAO) animal model. Furthermore, artemether treatment significantly suppressed cell apoptosis, stimulated cell proliferation and promoted the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), P90rsk and cAMP responsive element-binding protein (CREB). Artemether protective effect was attenuated by PD98059, an ERK1/2 inhibitor, administration. Similarly, in oxygen-glucose deprivation/reperfusion (OGD/RP) cell models, artemether pre-treatment induced the suppression of the intracellular ROS, the down-regulation of LDH activity, the reduction of caspase 3 activity and of the apoptosis cell rate and reversed the decrease of mitochondrial membrane potential. As with MCAO animal model, artemether promoted the activation of Erk1/2-P90rsk-CREB signaling pathway. This effect was blocked by the inhibition or knock-down of ERK1/2. The present study provides evidences of the neuroprotective effect of artemether unravelling its potential as a new therapeutic candidate for the prevention and treatment of stroke.The pharmaceutical equivalence between test (generic or similar) and reference medicine is evaluated through in vitro quality tests involving multiple compliance parameters. Despite efforts to ensure the reliability of the analytical results obtained in the pharmaceutical equivalence studies, measurement uncertainties lead to a risk of false decisions. Thus, the aim of this work was to evaluate the measurement uncertainties associated with the analytical results obtained in the pharmaceutical equivalence studies of different pharmaceutical forms and to estimate the risks of false decisions in the evaluation of pharmaceutical equivalence. The measurement uncertainties associated with the test results were evaluated using the bottom-up and top-down approaches. selleckchem The consumer’s or producer’s combined particular risks and combined total risks were estimated using the Monte Carlo method implemented in MS-Excel spreadsheet (available as supplemental material). Considering the seven pharmaceutical equivalence studies performed in this work, three studies were not conclusive (risk of false pharmaceutical equivalence decisions higher than 5 %). Moreover, we concluded pharmaceutical equivalence and pharmaceutical non-equivalence in one and three studies, respectively. The particular and total combined risks are useful to make decisions regarding the evaluation of pharmaceutical equivalence between the test (generic or similar) and reference medicines. Regulatory bodies and pharmaceutical equivalence centers are very interested in the estimation of the risks of false decisions, particularly to evaluate the quality of medicines that are not submitted to bioequivalence studies.As a kind of commonly used Traditional Chinese Medicine in clinical, Spatholobi Caulis (SPC) contains a wide variety of bioactive compounds, including protocatechuate (1), nicotinic acid (2), p-hydroxybenzoic acid (3), salicylic acid (4), 6,9-dihydroxy megastigma-4,7-dien-3-one (5), 8,9-dihydroxy megastigma-4,6-dien-3-one (6), daidzin (7), genistin (8), isolariciresinol (9), ononin (10), 4′,8-dimethoxy-7-O-β-d-glucopyranosyl isoflavone (11), 3′-methoxydaidzein (12), odoratin (13), spasuberol A (14), (+)-pinoresinol (15), 4-hydroxy-3-methoxy cinnamic acid methyl ester (16), (+)-epipinoresinol (17), calycosin (18), 8-O-methylretusin (19), formononetin sodium (20), formononetin (21), biochanin A (22), butesuperin A (23), homovanillyl-4-oxo-nonanoate (24) and (6aR,11aR)-maackiain (25). The pharmacokinetic characteristics of these twenty-five compounds in rat plasma were quantitatively and simultaneously studied using a fast, sensitive and precise ultra fast liquid chromatography combined with electrospray ionizat. This study provides reference values for the clinical application, in-depth study on new dosage forms and pharmacological activities of SPC.The radionuclides part of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) global network of International Monitoring System (IMS) is based on the measurement of particles and radioactive noble gases. Forty radionuclide stations are going to be equipped with radioxenon measurement components to monitor the nuclear explosion signatures around the world. Global coverage of the noble gas IMS stations has been investigated using atmospheric transport modelling. Two years of worldwide release for a hypothetical 1-kt underground nuclear explosion and detection of 133Xe in the IMS radioxenon station locations are considered. The present and completed status were supposed as two different scenarios to estimate the daily coverage of the network. The calculated quantities were evaluated corresponding to the whole latitude/longitude grid in image-base and numerical patterns. Although the fluctuation of daily coverage is varying in time, the cumulative minimum amounts were indicated that North America has stable high coverage in the present arrangement.