Plasma microRNAs as potential biomarkers for non-small-cell lung cancer

Non-small-cell lung cancer (NSCLC) is the leading cause of cancer-related death. Developing minimally invasive techniques that can diagnose NSCLC, particularly at an early stage, may improve its outcome. Using microarray platforms, we previously identified 12 microRNAs (miRNAs) the aberrant expressions of which in primary lung tumors are associated with early-stage NSCLC. Here, we extend our previous research by investigating whether the miRNAs could be used as potential plasma biomarkers for NSCLC. We initially validated expressions of the miRNAs in paired lung tumor tissues and plasma specimens from 28 stage I NSCLC patients by real-time quantitative reverse transcription PCR, and then evaluated diagnostic value of the plasma miRNAs in a cohort of 58 NSCLC patients and 29 healthy individuals. The altered miRNA expressions were reproducibly confirmed in the tumor tissues. The miRNAs were stably present and reliably measurable in plasma. Of the 12 miRNAs, five displayed significant concordance of the expression levels in plasma and the corresponding tumor tissues (all r>0.850, all P<0.05). A logistic regression model with the best prediction was defined on the basis of the four genes (miRNA-21, -126, -210, and 486-5p), yielding 86.22% sensitivity and 96.55% specificity in distinguishing NSCLC patients from the healthy controls. Furthermore, the panel of miRNAs produced 73.33% sensitivity and 96.55% specificity in identifying stage I NSCLC patients. In addition, the genes have higher sensitivity (91.67%) in diagnosis of lung adenocarcinomas compared with squamous cell carcinomas (82.35%) (P<0.05). Altered expressions of the miRNAs in plasma would provide potential blood-based biomarkers for NSCLC

Diagnosis of lung cancer in individuals with solitary pulmonary nodules by plasma microRNA biomarkers

<p>Abstract</p> <p>Background</p> <p>Making a definitive preoperative diagnosis of solitary pulmonary nodules (SPNs) found by CT has been a clinical challenge. We previously demonstrated that microRNAs (miRNAs) could be used as biomarkers for lung cancer diagnosis. Here we investigate whether plasma microRNAs are useful in identifying lung cancer among individuals with CT-detected SPNs.</p> <p>Methods</p> <p>By using quantitative reverse transcriptase PCR analysis, we first determine plasma expressions of five miRNAs in a training set of 32 patients with malignant SPNs, 33 subjects with benign SPNs, and 29 healthy smokers to define a panel of miRNAs that has high diagnostic efficiency for lung cancer. We then validate the miRNA panel in a testing set of 76 patients with malignant SPNs and 80 patients with benign SPNs.</p> <p>Results</p> <p>In the training set, miR-21 and miR-210 display higher plasma expression levels, whereas miR-486-5p has lower expression level in patients with malignant SPNs, as compared to subjects with benign SPNs and healthy controls (all P ≤ 0.001). A logistic regression model with the best prediction was built on the basis of miR-21, miR-210, and miR-486-5p. The three miRNAs used in combination produced the area under receiver operating characteristic curve at 0.86 in distinguishing lung tumors from benign SPNs with 75.00% sensitivity and 84.95% specificity. Validation of the miRNA panel in the testing set confirms their diagnostic value that yields significant improvement over any single one.</p> <p>Conclusions</p> <p>The plasma miRNAs provide potential circulating biomarkers for noninvasively diagnosing lung cancer among individuals with SPNs, and could be further evaluated in clinical trials.</p

Sisymbrium linifolium and Sisymbriopsis schugnana (Brassicaceae), two new records from Xinjiang, China

Sisymbrium linifolium and Sisymbriopsis schugnana, previously confined to western North America and Tajikistan, respectively, were discovered in Xinjiang during a recent field trip to this autonomous region of China. The identity of these two species was subsequently confirmed by extensive morphological and molecular studies. The biogeographical significance of these new floristic records is briefly addressed

New insights into the taxonomy of tribe Euclidieae (Brassicaceae), evidence from nrITS sequence data

As currently delimitated, the species-rich mustard tribe Euclidieae DC. (Brassicaceae) comprises 28 genera and 152 species distributed primarily in Asia. To date, no tribe-wide comprehensive phylogenetic analysis has been conducted. In this study, sequence data from the nuclear ribosomal internal transcribed spacer (nrITS) region of 82 species in all 28 genera of Euclidieae were used to test its monophyly and infer inter- and intra-generic relationships within. Phylogenetic analyses revealed that Rhammatophyllum and Sisymbriopsis are embedded within Solms-laubachia s.l., and Solms-laubachia lanuginosa (Eurycarpus lanuginosus) fell outside the tribe. Therefore, Solms-laubachia s.l. as currently recognized is not monophyletic and its generic delimitation needed further study. Besides, our results suggest that the genera Lepidostemon, Neotorularia, and Tetracme are polyphyletic

Sisymbrium linifolium and Sisymbriopsis schugnana (Brassicaceae), two new records from Xinjiang, China

Sisymbrium linifolium and Sisymbriopsis schugnana, previously confined to western North America and Tajikistan, respectively, were discovered in Xinjiang during a recent field trip to this autonomous region of China. The identity of these two species was subsequently confirmed by extensive morphological and molecular studies. The biogeographical significance of these new floristic records is briefly addressed

Molecular phylogeny reveals the non-monophyly of tribe Yinshanieae (Brassicaceae) and description of a new tribe, Hillielleae

The taxonomic treatment within the unigeneric tribe Yinshanieae (Brassicaceae) is controversial, owing to differences in generic delimitation applied to its species. In this study, sequences from nuclear ITS and chloroplast trnL-F regions were used to test the monophyly of Yinshanieae, while two nuclear markers (ITS, ETS) and four chloroplast markers (trnL-F, trnH-psbA, rps16, rpL32-trnL) were used to elucidate the phylogenetic relationships within the tribe. Using maximum parsimony, maximum likelihood, and Bayesian inference methods, we reconstructed the phylogeny of Brassicaceae and Yinshanieae. The results show that Yinshanieae is not a monophyletic group, with the taxa splitting into two distantly related clades: one clade contains four taxa and falls in Lineage I, whereas the other includes all species previously placed in Hilliella and is embedded in the Expanded Lineage II. The tribe Yinshanieae is redefined, and a new tribe, Hillielleae, is proposed based on combined evidence from molecular phylogeny, morphology, and cytology

Mechanistic study of the ligand controlled regioselectivity in iridium catalyzed C- H borylation of aromatic imines

As a major challenge in C-H borylation, how to control the selectivity has attracted lots of attention, however, the related mechanistic information still needs to be uncovered. Herein, density functional theory (DFT) has been used to study the mechanism for the ligand controlled regioselectivity in the iridium-catalyzed C-H borylation of aromatic imines, which is inspired by experimental observations (R. Bisht, B. Chattopadhyay, J. Am. Chem. Soc., 2016, 138, 84-87). The proposed Ir(i)-Ir(iii) catalytic cycle includes (i) the oxidative addition of the C-H bond to iridium(i); (ii) the reductive elimination of a C-B bond; (iii) the oxidative addition of B(2)pin(2) to an iridium(i) hydride complex; and (iv) the reductive elimination of a B-H bond. The oxidative addition of a C-H bond to the iridium center is the determining step. For the ligand AQ, ortho-selectivity is proposed to be attributed to the decreased steric hindrance and increased electron donating effect of AQ (8-aminoquinoline) which promotes proton-transfer in the ortho-transition state of C-H activation. While, for the TMP ligand, the steric repulsion between the TMP (4,5,7,8-tetramethyl-1, 10-phenanthroline) ligand and the ortho-substituted imine hinders the ortho C-H activation and favors meta borylation. Our calculations provide insights into further ligand design to achieve different regioselective borylation of aromatics. Guided by the results, the regioselectivity in the borylation of aromatics may be achieved by accordingly modifying the electronic and steric substituents of the ligand

Apoptosis induced by Ginkgo biloba (EGb761) in melanoma cells is Mcl-1-dependent.

Melanoma is an aggressive skin cancer. Unfortunately, there is currently no chemotherapeutic agent available to significantly prolong the survival of the most patients with metastatic melanomas. Here we report that the Ginkgo biloba extract (EGb761), one of the most widely sold herbal supplements in the world, potently induces apoptosis in human melanoma cells by disturbing the balance between pro- and anti-apoptosis Bcl-2 family proteins. Treatment with EGb761 induced varying degrees of apoptosis in melanoma cell lines but not in melanocytes. Induction of apoptosis was caspase-dependent and appeared to be mediated by the mitochondrial pathway, in that it was associated with reduction in mitochondrial membrane potential and activation of Bax and Bak. Although EGb761 did not cause significant change in the expression levels of the BH3-only Bcl-2 family proteins Bim, Puma, Noxa, and Bad, it significantly downregulated Mcl-1 in sensitive but not resistant melanoma cells, suggesting a major role of Mcl-1 in regulating apoptosis of melanoma cells induced by EGb761. Indeed, siRNA knockdown of Mcl-1 enhanced EGb761-induced apoptosis, which was associated with increased activation of Bax and Bak. Taken together, these results demonstrate that EGb761 kills melanoma cells through the mitochondrial apoptotic pathway, and that Mcl-1 is a major regulator of sensitivity of melanoma cells to apoptosis induced by EGb761. Therefore, EGb761 with or without in combination with targeting Mcl-1 may be a useful strategy in the treatment of melanoma

Magma chamber-related transition from magmatic to solid-state fabrics within the Late Triassic granitic Dushan pluton (North China)

International audienceSUMMARY Penetrative petro-fabrics in plutons, particularly late-stage solid-state fabrics, are usually considered to record regional tectonism. However, these fabrics are fundamentally ambiguous to correlate with magma-chamber processes or regional tectonics. Understanding the processes of fabric formation requires a proper understanding of pluton formation and emplacement mechanism. In this paper, we provide a case study of a transition from magma chamber-related magmatic to solid-state fabrics within the Late Triassic granitic Dushan pluton (North China) based on a multidisciplinary investigation of its emplacement mechanism, including structural geology, isotope chronology, AMS data measurement, and gravity modeling. The Dushan pluton varies in a southwest direction from a megascopically isotropic monzogranite in the northeast to an arc-shaped gneissic monzogranite with locally mylonitic zones along the southwest margin. The compatible outward dipping mesoscopic and magnetic susceptibility foliations define a dome-like roof with a NE-SW long axis. Considering the absence of similar penetrative fabrics in the country rocks, a continuum of magma chamber-related fabric variations within the pluton, from magmatic to solid-state conditions, probably formed during pluton emplacement. Gravity modeling suggests that the Dushan pluton has a NE-SW trending tongue-like shape with a northeast positioned root. We propose a model in which the Dushan pluton was emplaced through a northeast feeder zone, beginning probably as a sill then evolving by inflation via several magma batches. Later magma batches inflated the country rocks to form the final pluton. Magma inflation deformed the former semi-solid magma, forming a curved gneissic to mylonitic foliation along the southwest margin of the pluton. Several multidisciplinary studies show that the North China Craton (NCC) experienced a Late Triassic regional crustal extension attending the Dushan pluton emplacement. Both mesoscopic and magnetic susceptibility fabrics of the pluton could be more related to magmatic process rather than regional tectonics, implying that such fabrics within plutons need to be used with caution for inferring regional tectonics