ABSTRACT
The purpose of this study was to evaluate the role of 2-D speckle tracking imaging in assessing left ventricular diastolic function in patients with connective tissue disease (CTD). A total of 98 CTD patients and 32 healthy controls were prospectively recruited. Early (E) and late (A) diastolic velocities of the transmitral flow were measured by pulsed Doppler echocardiography. Peak early diastolic myocardial velocity (E') was calculated on tissue Doppler echocardiography. The longitudinal strain rate (SR) was calculated as the average of three apical views, while circumferential and radial SRs were measured in three short-axis views. Pulmonary arterial hypertension (PAH) was defined as systolic pulmonary arterial pressure (sPAP) >36 mm Hg. Compared with the control group, CTD patients exhibited significant impairment of left ventricular diastolic function, manifested as lower global SR during early diastole (SRe) in the longitudinal deformation and higher E/SRe in both longitudinal and radial deformation. CTD-PAH patients had significantly lower SRe and higher E/SRe values in both the longitudinal and radial deformation compared with the patients with CTD without PAH. Pearson's correlation analysis revealed that sPAP levels correlated positively with E/E', longitudinal E/SRe, circumferential E/SRe and radial SRe, and it correlated negatively with septal E' and radial E/SRe. Receiver operating characteristic curve analysis suggested that E/E', longitudinal E/SRe and radial SRe could be used to predict PAH. The present study indicates that 2-D speckle tracking imaging is a useful method for evaluation of left ventricular diastolic function, and these derived parameters can serve as good predictors of PAH, but it may not be superior to the commonly used E/E' in CTD patients.
Subject(s)
Connective Tissue Diseases/physiopathology , Echocardiography/methods , Pulmonary Arterial Hypertension/physiopathology , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/physiopathology , Adult , Blood Flow Velocity , Case-Control Studies , Connective Tissue Diseases/complications , Diastole , Female , Humans , Male , Middle Aged , Observer Variation , Prospective Studies , Pulmonary Arterial Hypertension/etiology , ROC Curve , Reproducibility of Results , Ventricular Dysfunction, Left/etiologyABSTRACT
A new 19-oxo-18,19-seco-ursane-type triterpeonoid saponin, laevigin E (8), together with 17 known compounds (1 - 7 and 9 - 18) were isolated from the root bark of Ilex rotunda Thunb. Their structures were determined by various spectroscopic analysis. Among them, compounds 6, 9, 11, and 18 were isolated from this species for the first time, while compounds 10 and 12 were firstly isolated from the family Aquifoliaceae. Biological activity assay showed that all triterpenoids exhibit moderate cytotoxic activities against MCF7, A549, HeLa and LN229 cell lines. The four triterpenoid saponins (3, 4, 6, and 8) exhibit slightly better activities compared to the four triterpenoid sapogenins (1, 2, 5, and 7). Compound 8 showed the best cytotoxicity against A549, HeLa and LN229 cell lines with IC50 of 17.83, 22.58 and 30.98 µm, respectively.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Cell Proliferation/drug effects , Ilex/chemistry , Plant Bark/chemistry , Plant Roots/chemistry , Saponins/pharmacology , Triterpenes/pharmacology , HeLa Cells , Humans , Molecular StructureABSTRACT
We obtain an expectation formula and give the probabilistic proofs of some summation and transformation formulas of q-series based on our expectation formula. Although these formulas in themselves are not the probability results, the proofs given are based on probabilistic concepts.
Subject(s)
Models, Statistical , ProbabilityABSTRACT
The ellipsoid egg, the second recessive gene of chocolate larvae, and melanism are controlled by three recessive genes, elp, ch-2, and mln in silkworm, respectively. Their order and genetic distance have been scheduled in established linkage group. Owing to lack of crossing over in females, the reciprocal backcrossed F1(BC1) progenies were bred for linkage analysis using the wild type silkworm strain P50(+elp+ch-2+mln /+elp+ch-2+mln) and W18 with ellipsoid egg, the second recessive gene of chocolate larvae, and melanism (elp ch-2 mln / elp ch-2 mln). In this research, we mapped three mutant genes, elp, ch-2, and mln on the chromosome 18 based on the SSR linkage map and STS markers designed based on silkworm genome sequence. The established linkage group, molecular linkage group, and the physic map of chromosome 18 had been corresponded. The genetic distance for this chromosome in this research was 94.2 cM, and the order of the mutants and molecular markers were consistent with the established silkworm linkage maps and the fine genome sequences. This research will lay important bases for map-based cloning for other mutants on chromosome 18.
Subject(s)
Bombyx/genetics , Chromosome Mapping , Chromosomes, Insect , Genes, Insect , Genes, Recessive , Genetic Linkage , Animals , Crossing Over, Genetic , Female , Genetic Markers , Male , PhenotypeABSTRACT
The insulin-like growth factor I receptor (IGFIR) has emerged as a key therapeutic target in many human malignancies, including childhood cancers such as Ewing family tumors (EFT). In this study, we show that IGFIR is constitutively activated in EFTs and that the major catechin derivative found in green tea, (-)-epigallocatechin gallate (EGCG), can inhibit cell proliferation and survival of EFT cells through the inhibition of IGFIR activity. Treatment of EFT cell lines with EGCG blocked the autophosphorylation of IGFIR tyrosine residues and inhibited its downstream pathways including phosphoinositide 3-kinase-Akt, Ras-Erk, and Jak-Stat cascades. EGCG treatment was associated with dose- and time-dependent inhibition of cellular proliferation, viability, and anchorage-independent growth, as well as with the induction of cell cycle arrest and apoptosis. Apoptosis in EFT cells by EGCG correlated with altered expression of Bcl-2 family proteins, including increased expression of proapoptotic Bax and decreased expression of prosurvival Bcl2, Bcl-XL, and Mcl-1 proteins. Our results provide further evidence that IGFIR is an attractive therapeutic target in EFTs and that EGCG is an effective inhibitor of this receptor tyrosine kinase. EGCG may be a useful agent for targeting IGFIR, either alone or in combination, with other potentially more toxic IGFIR inhibitors for the management of EFTs.
Subject(s)
Bone Neoplasms/pathology , Catechin/analogs & derivatives , Cell Proliferation/drug effects , Receptor, IGF Type 1/antagonists & inhibitors , Sarcoma, Ewing/pathology , Anticarcinogenic Agents/pharmacology , Apoptosis/drug effects , Catechin/pharmacology , Cell Adhesion/drug effects , Cell Death/drug effects , Cell Line, Tumor , Cells, Cultured , Drug Evaluation, Preclinical , Humans , MAP Kinase Signaling System/drug effects , Oncogene Protein v-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Phosphorylation/drug effects , Receptor, IGF Type 1/metabolismABSTRACT
RNA interference (RNAi) is rapidly becoming the method of choice for the elucidation of gene function and the identification of drug targets. As with other oligonucleotide-based strategies, RNAi is envisioned to ultimately be useful as a human therapeutic. Unlike previous nucleic acid therapeutics, small interfering RNAs have the potential to elicit immune responses via interactions with Toll-like receptor 3 and trigger interferon responses like long, double-stranded RNA and its analogs, such as poly(I:C). Recently, the safety of siRNAs has been questioned because they have been shown to trigger an interferon response in cultured cells. We show here that it is possible to administer naked, synthetic siRNAs to mice and downregulate an endogenous or exogenous target without inducing an interferon response.
