ZEB1 induces LOXL2-mediated collagen stabilization and deposition in the extracellular matrix to drive lung cancer invasion and metastasis.

Lung cancer is the leading cause of cancer-related deaths, primarily due to distant metastatic disease. Metastatic lung cancer cells can undergo an epithelial-to-mesenchymal transition (EMT) regulated by various transcription factors, including a double-negative feedback loop between the microRNA-200 (miR-200) family and ZEB1, but the precise mechanisms by which ZEB1-dependent EMT promotes malignancy remain largely undefined. Although the cell-intrinsic effects of EMT are important for tumor progression, the reciprocal dynamic crosstalk between mesenchymal cancer cells and the extracellular matrix (ECM) is equally critical in regulating invasion and metastasis. Investigating the collaborative effect of EMT and ECM in the metastatic process reveals increased collagen deposition in metastatic tumor tissues as a direct consequence of amplified collagen gene expression in ZEB1-activated mesenchymal lung cancer cells. In addition, collagen fibers in metastatic lung tumors exhibit greater linearity and organization as a result of collagen crosslinking by the lysyl oxidase (LOX) family of enzymes. Expression of the LOX and LOXL2 isoforms is directly regulated by miR-200 and ZEB1, respectively, and their upregulation in metastatic tumors and mesenchymal cell lines is coordinated to that of collagen. Functionally, LOXL2, as opposed to LOX, is the principal isoform that crosslinks and stabilizes insoluble collagen deposition in tumor tissues. In turn, focal adhesion formation and FAK/SRC signaling is activated in mesenchymal tumor cells by crosslinked collagen in the ECM. Our study is the first to validate direct regulation of LOX and LOXL2 by the miR-200/ZEB1 axis, defines a novel mechanism driving tumor metastasis, delineates collagen as a prognostic marker, and identifies LOXL2 as a potential therapeutic target against tumor progression.

The miR-200 family and the miR-183~96~182 cluster target Foxf2 to inhibit invasion and metastasis in lung cancers.

Metastatic lung cancer is one of the most lethal forms of cancer and molecular pathways driving metastasis are still not clearly elucidated. Metastatic cancer cells undergo an epithelial-mesenchymal transition (EMT) where they lose their epithelial properties and acquire a migratory and invasive phenotype. Here we identify that the expression of microRNAs from the miR-200 family and the miR-183~96~182 cluster are significantly co-repressed in non-small cell lung cancer cell lines and primary tumors from multiple TCGA dataset with high EMT scores. Ectopic expression of the miR-183~96~182 cluster inhibited cancer cell migration and invasion, whereas its expression was tightly modulated by miR-200. We identified Foxf2 as a common, novel and direct target of both these microRNA families. Foxf2 expression tightly correlates with the transcription factor Zeb1 and is elevated in mesenchymal-like metastatic lung cancer cells. Foxf2 expression induced robust EMT, migration, invasion and metastasis in lung cancer cells, whereas Foxf2 inhibition significantly repressed these phenotypes. We also demonstrated that Foxf2 transcriptionally represses E-cadherin and miR-200, independent of Zeb1, to form a double-negative feedback loop. We, therefore, identified a novel mechanism whereby the miR-200 family and the miR-183~96~182 cluster inhibit lung cancer invasion and metastasis by targeting Foxf2.

SunSmart: evaluation of a pilot school-based sun protection intervention in Hispanic early adolescents.

The incidence of melanoma is rising among Hispanic populations in the United States. The purpose of this study is to evaluate the impact of a pilot sun safety educational intervention conducted from 2006 to 2012 on Hispanic early adolescents in a high ultraviolet environment. Nineteen schools with high Hispanic enrollment were recruited from urban neighborhoods in Los Angeles. The analytic sample was restricted to students identifying as Hispanic or Latino (n = 777). A mixed effects linear model was used to test mean changes from pre- to posttest on students' sun protection knowledge, attitudes and behaviors. Significant improvements were observed across several cognitive outcomes related to sun protection, including knowledge of and attitudes toward sun protection and self-efficacy to wear sunscreen. However, changes in sun protective behaviors were not achieved. Although some improvements were observed, future studies should identify the factors that motivate sun protection in this population and develop tailored prevention strategies, as improving the sun safe behaviors of Hispanic youths may aid in reducing the risk of melanoma in adulthood in this population.

Value of dual-source computed tomography in evaluating left ventricular function in patients with coronary heart disease.

We aimed to assess parameters reflecting left ventricular function by dual-source computed tomography (DSCT) with echocardiography (ECG) as control. Fifty-eight patients with coronary heart disease (CHD) were recruited from January to June 2011; 29 CHD patients had type II diabetes. All patients were assessed by cardiac DSCT and ECG examination. DSCT and ECG correlated well for ejection fraction (EF) (r = 0.70), end-systolic volume (ESV) (r = 0.87), stroke volume (SV) (r = 0.83), and end-diastolic volume (EDV) (r = 0.90). The mean ESV and EDV values measured by the two methods in CHD patients with type II diabetes were higher than those in non-diabetic patients, whereas the mean EF was lower. DSCT is an accurate and practical method for assessing left ventricular function.

[Effect of 3,4-dihydroxyacetophenone on phospholipid components of platelet membrane in aged rats].

3,4-Dihydroxyacetophenone (DHAP) is one of the constituents of Ilex pubescence Hook. et Arn. var. glaber Chang. The effects of DHAP on the composition of blood platelet membrane in aged rats was examined. No change of total lipid and cholesterol contents was observed in aged rats. While a slight but significant decrease of phospholipid in platelet membrane was found, which lead to diminution of the ratio of phospholipid to cholesterol. The contents of phosphatidylethanolamine and phosphatidylcholine decreased markedly by as less as 23.0% and 19%, respectively, compared with the young group. Whereas the degree of reduction of phospholipid, the ratio of phospholipid to cholesterol, phosphatidylethanolamine and phosphatidylcholine were significantly lightened after irrigation with DHAP 100 mg.kg-1 for 10 weeks. In the treatment group, the values of phosphatidylethanolamine and phosphatidylcholine of platelet membrane were reduced by 8.0% and 10.5%, respectively, vs the group of aged rats. It is concluded that reduced phospholipid hydrolysis is involved in mediating DHAP inhibition of platelet function.

[Ultrastructural observation on the spermiogenesis of Pagumogonimus skrjabini].

The spermiogenesis of Pagumogonimus skrjabini was observed on the ultrastructural level by transmission electron microscopy. The development and the morphological characteristics of spermatids and sperm were studied. The Golgi comples was located near the anterior region of the spermatid nucleus and developed into an acrosomal cap of the sperm. Accordingly, an acrosomal structure of P. skrjabini was recognized in this study. The mature sperm of P.s. was composed of head and tail. The head part was filled with dense nucleus and the nucleoplasma extended into the anterior end of the median part of the sperm tail. A conjunction part was seen between the head and the tail. The tail was composed of a median part and a terminal part. At the beginning of median part of the tail, two axial filaments were found on each side. Each axial filament was composed of two central filaments and nine pairs of cuter filaments. The two central filaments were surrounded by fibrous sheath, both of which were connected with spoke-like structures. Mitochondria were arranged in a line in the ventral portion of the central filaments. At the terminal part of the tail, two axial filaments lay closely together.

[Symptomatic case findings of pulmonary tuberculosis].

One of the major way to find pulmonary tuberculosis cases, especially cases with positive sputum, is "by symptoms". This clinic, together with the medical staffs at various health institutions, took five years to set up a tbc finding network in this city. The definite range of duties and a series of grading and examining criteria were put out. This efficient network shortened the average time that patients were transferred from general hospitals to antituberculosis clinic from 34.6 days in 1983 to 19.4 days in 1987. Consequently, the rate of medical delay decreased also, from 40.5% to 33.0%. Although the prevalence rate of tbc. cases reduced yearly in this city, the case finding rate of patients with positive sputum increased, from 1.5/10,000 to 2.0/10,000. It is confirmed by 5 years' practice that this network could raise the efficacy of case finding.

[Ultrastructural observation on the body wall of Pagumogonimus skrjabini].

This paper deals with the ultrastructure of the body wall of adult Pagumogonimus skrjabini by transmission electron microscopy. Infected crabs were collected from Siyen, Hubei Province, and adult worms were obtained from the lungs of experimentally infected dogs 90 days post-infection. The normal structure of body wall of the P. skrjabini is composed of tegument, tegument cell, muscle muscle cell and protoplasmic tubules, all of which form together syncytium. The tegument contains external plasma membrane, tegument matrix and basal plasma membrane. The cell coat in fine granules is distributed over the whole external plasma membrane surface. The tegument matrix contains various secretory bodies, vesicles and mitochondria. The tegument cell is irregular in shape. Golgi complex, ribosome, autolysosome are seen in the cytoplasm. There are two layers of muscle, the external circular muscle and the inner longitudinal muscle layers. The nucleus of immature muscle cell has many heterochromatins, while the nucleus of mature muscle cell is large and round in shape. Mitochondria and glycogen granules are transmitted from muscle cell proper to the muscle by protoplasmic tubules (Figs. 1 approximately 7).