Pulmonary diseases induced by ambient ultrafine and engineered nanoparticles in twenty-first century.

Air pollution is a severe threat to public health globally, affecting everyone in developed and developing countries alike. Among different air pollutants, particulate matter (PM), particularly combustion-produced fine PM (PM2.5) has been shown to play a major role in inducing various adverse health effects. Strong associations have been demonstrated by epidemiological and toxicological studies between increases in PM2.5 concentrations and premature mortality, cardiopulmonary diseases, asthma and allergic sensitization, and lung cancer. The mechanisms of PM-induced toxicological effects are related to their size, chemical composition, lung clearance and retention, cellular oxidative stress responses and pro-inflammatory effects locally and systemically. Particles in the ultrafine range (<100 nm), although they have the highest number counts, surface area and organic chemical content, are often overlooked due to insufficient monitoring and risk assessment. Yet, ample studies have demonstrated that ambient ultrafine particles have higher toxic potential compared with PM2.5. In addition, the rapid development of nanotechnology, bringing ever-increasing production of nanomaterials, has raised concerns about the potential human exposure and health impacts. All these add to the complexity of PM-induced health effects that largely remains to be determined, and mechanistic understanding on the toxicological effects of ambient ultrafine particles and nanomaterials will be the focus of studies in the near future

Down-regulation of F-actin and paxillin by N-(3-(1Htetrazol- 1-yl)phenyl) isonicotinamide derivative inhibits proliferation of prostate cancer cells

Purpose: To investigate the effect of N-(3-(1H-tetrazol-1-yl)phenyl) isonicotinamide derivative (TPIN) on prostate cancer cells, and the mechanism involved.Methods: The cytotoxicity of TPIN in DU145 and PC3 cells was determined using Cell Counting Kit-8, while apoptosis induction was assayed by flow cytometry using Annexin V-fluorescein isothiocyanate dye. Changes in expressions of F-actin, RAC-α and paxillin were determined by western blot assay.Results: Cell proliferation was effectively inhibited by TPIN in the concentration range of 0.75-15 μM. The values of half-minimum inhibitory concentration (IC50) of TPIN for DU145 and PC3 cells at 48 h were 5.6 and 10.2 μM, respectively (p < 0.05). Treatment with 5.6 μM TPIN increased apoptosis to 59.64 % in DU145 cells, and 54.21% in PC3 cells. Cleaved caspase-3 and caspase-9 levels were increased by TPIN treatment in both cell lines (p < 0.05). Moreover, the levels of F-actin and paxillin were significantly downregulated by TPIN treatment in DU145 and PC3 cells (p < 0.05). In TPIN-treated DU145 and PC3 cells, cofilin-1expression was up-regulated, relative to control cells.Conclusion: TPIN exhibits cytotoxic effect on prostate cancer cells via activation of apoptosis. It elevates cofilin-1 and the expressions of targets F-actin and paxillin in prostate cancer cells. Thus, TPIN is a potential chemotherapeutic agent for prostate cancer. However, further investigations, including clinical trials are required to authenticate these findings. Keywords: Prostate cancer, F-actin, Paxillin, Apoptosis, Caspase

Monofunctional Platinum-DNA Adducts Are Strong Inhibitors of Transcription and Substrates for Nucleotide Excision Repair in Live Mammalian Cells

To overcome drug resistance and reduce the side effects of cisplatin, a widely used antineoplastic agent, major efforts have been made to develop next generation platinum-based anticancer drugs. Because cisplatin–DNA adducts block RNA polymerase II unless removed by transcription-coupled excision repair, compounds that react similarly but elude repair are desirable. The monofunctional platinum agent pyriplatin displays antitumor activity in mice, a cytotoxicity profile in cell cultures distinct from that of cisplatin, and a unique in vitro transcription inhibition mechanism. In this study, we incorporated pyriplatin globally or site specifically into luciferase reporter vectors to examine its transcription inhibition profiles in live mammalian cells. Monofunctional pyriplatin reacted with plasmid DNA as efficiently as bifunctional cisplatin and inhibited transcription as strongly as cisplatin in various mammalian cells. Using repair-defective nucleotide excision repair (NER)-, mismatch repair-, and single-strand break repair–deficient cells, we show that NER is mainly responsible for removal of pyriplatin–DNA adducts. These findings reveal that the mechanism by which pyriplatin generates its antitumor activity is very similar to that of cisplatin, despite the chemically different nature of their DNA adducts, further supporting a role for monofunctional platinum anticancer agents in human cancer therapy. This information also provides support for the validity of the proposed mechanism of action of cisplatin and provides a rational basis for the design of more potent platinum anticancer drug candidates using a monofunctional DNA-damaging strategy.National Cancer Institute (U.S.) (Grant Number CA034992

Single nucleotide polymorphisms of one-carbon metabolism and cancers of the esophagus, stomach, and liver in a Chinese population.

One-carbon metabolism (folate metabolism) is considered important in carcinogenesis because of its involvement in DNA synthesis and biological methylation reactions. We investigated the associations of single nucleotide polymorphisms (SNPs) in folate metabolic pathway and the risk of three GI cancers in a population-based case-control study in Taixing City, China, with 218 esophageal cancer cases, 206 stomach cancer cases, 204 liver cancer cases, and 415 healthy population controls. Study participants were interviewed with a standardized questionnaire, and blood samples were collected after the interviews. We genotyped SNPs of the MTHFR, MTR, MTRR, DNMT1, and ALDH2 genes, using PCR-RFLP, SNPlex, or TaqMan assays. To account for multiple comparisons and reduce the chances of false reports, we employed semi-Bayes (SB) shrinkage analysis. After shrinkage and adjusting for potential confounding factors, we found positive associations between MTHFR rs1801133 and stomach cancer (any T versus C/C, SB odds-ratio [SBOR]: 1.79, 95% posterior limits: 1.18, 2.71) and liver cancer (SBOR: 1.51, 95% posterior limits: 0.98, 2.32). There was an inverse association between DNMT1 rs2228612 and esophageal cancer (any G versus A/A, SBOR: 0.60, 95% posterior limits: 0.39, 0.94). In addition, we detected potential heterogeneity across alcohol drinking status for ORs relating MTRR rs1801394 to esophageal (posterior homogeneity P = 0.005) and stomach cancer (posterior homogeneity P = 0.004), and ORs relating MTR rs1805087 to liver cancer (posterior homogeneity P = 0.021). Among non-alcohol drinkers, the variant allele (allele G) of these two SNPs was inversely associated with the risk of these cancers; while a positive association was observed among ever-alcohol drinkers. Our results suggest that genetic polymorphisms related to one-carbon metabolism may be associated with cancers of the esophagus, stomach, and liver. Heterogeneity across alcohol consumption status of the associations between MTR/MTRR polymorphisms and these cancers indicates potential interactions between alcohol drinking and one-carbon metabolic pathway

Air pollution dispersion from biomass stoves to neighboring homes in Mirpur, Dhaka, Bangladesh.

BACKGROUND: Indoor air pollution, including fine particulate matter (PM2.5) and carbon monoxide (CO), is a major risk factor for pneumonia and other respiratory diseases. Biomass-burning cookstoves are major contributors to PM2.5 and CO concentrations. However, high concentrations of PM2.5 (> 1000 μg/m3) have been observed in homes in Dhaka, Bangladesh that do not burn biomass. We described dispersion of PM2.5 and CO from biomass burning into nearby homes in a low-income urban area of Dhaka, Bangladesh. METHODS: We recruited 10 clusters of homes, each with one biomass-burning (index) home, and 3-4 neighboring homes that used cleaner fuels with no other major sources of PM2.5 or CO. We administered a questionnaire and recorded physical features of all homes. Over 24 h, we recorded PM2.5 and CO concentrations inside each home, near each stove, and outside one neighbor home per cluster. During 8 of these 24 h, we conducted observations for pollutant-generating activities such as cooking. For each monitor, we calculated geometric mean PM2.5 concentrations at 5-6 am (baseline), during biomass burning times, during non-cooking times, and over 24 h. We used linear regressions to describe associations between monitor location and PM2.5 and CO concentrations. RESULTS: We recruited a total of 44 homes across the 10 clusters. Geometric mean PM2.5 and CO concentrations for all monitors were lowest at baseline and highest during biomass burning. During biomass burning, linear regression showed a decreasing trend of geometric mean PM2.5 and CO concentrations from the biomass stove (326.3 μg/m3, 12.3 ppm), to index home (322.7 μg/m3, 11.2 ppm), neighbor homes sharing a wall with the index home (278.4 μg/m3, 3.6 ppm), outdoors (154.2 μg/m3, 0.7 ppm), then neighbor homes that do not share a wall with the index home (83.1 μg/m3,0.2 ppm) (p = 0.03 for PM2.5, p = 0.006 for CO). CONCLUSION: Biomass burning in one home can be a source of indoor air pollution for several homes. The impact of biomass burning on PM2.5 or CO is greatest in homes that share a wall with the biomass-burning home. Eliminating biomass burning in one home may improve air quality for several households in a community

Herramienta pedag?gica para la ense?anza de las ciencias naturales

48 P?ginasRecurso Electr?nicoEl presente proyecto est? basado en la implementaci?n de una Herramienta Pedag?gica en el ?rea de las Ciencias Naturales en el grado s?ptimo (A, B y C) de la Instituci?n Escuela Normal Superior Santa Teresita. Esta instituci?n no cuenta con proyectos sobre las herramientas pedag?gicas, pero es de resaltar que la instituci?n es netamente pedag?gica y que se fundamenta en el pedagogo Celestin Freinet, el cual plantea el texto libre y la UAI. Teniendo en cuenta los Lineamientos curriculares, los cuales proponen ejes fundamentales como son los procesos de pensamiento y acci?n y conocimiento cient?fico b?sico, se realiza la Cartilla ?EXPLOREMOS 7?? ?La C?lula?, con el fin de que los estudiantes participen de un aprendizaje activo y significativo. Para la realizaci?n de este proyecto, las investigadoras se centraron en varios autores como Koock, Ville, Helena Curt?s, Sneider y Chowan, quienes dieron aportes significativos a esta tesis de grado. Con esta Herramienta Pedag?gica se busca mejorar los procesos de aprendizaje de los estudiantes, mejorando la actividad educativa evidenciando mediante la pr?ctica resultados positivos de aprendizaje.ABSTRACT. This project is based on the implementation of a Pedagogical Tool in the area of natural science in seventh grade (A, B and C) of the Superior Normal School Institution Theresa. This institution has no projects on educational tools, but it is noteworthy that the institution is purely educational and is based on the pedagogue Celestin Freinet, which raises the free text and IAU. Given the curriculum guidelines, which are proposed as the cornerstones of thought and action processes and basic scientific knowledge, the Primer is done "EXPLORATIONS 7th" "The Cell" in order to engage students in learning active and meaningful. For this project, the researchers focused on several authors as Koock, Ville, Helena Curtis, Sneider and Chowan, who gave significant contributions to this thesis. This pedagogical tool is to improve the learning processes of students, improving the educational activity showing positive results through practical learning.INTRODUCCI?N 11 1. MARCO CONTEXTUAL 12 2. ANTECEDENTES 13 3. FORMULACI?N DEL PROBLEMA 15 4. PREGUNTA PROBLEMATIZADORA 16 5. JUSTIFICACI?N 17 6. OBJETIVOS 18 6.1 OBJETIVO GENERAL 18 6.2 OBJETIVOS ESPEC?FICOS 18 7. MARCO TE?RICO 19 7.1 LEY GENERAL DE EDUCACI?N 19 7.2 LINEAMIENTOS Y EST?NDARES CURRICULARES 19 7.2.1 Procesos de pensamiento y acci?n grado s?ptimo 20 7.2.2 Conocimiento de procesos biol?gicos 20 7.3 CONSTRUCTIVISMO 21 7.4 DID?CTICA 21 7.5 ESTRATEGIA 22 7.6 ESTRATEGIAS DID?CTICAS 23 7.7 APRENDIZAJE SIGNIFICATIVO 23 7.8 ENSE?ANZA 26 7.9 PEDAGOG?AS ACTIVAS 26 7.10 CELESTIN FREINET 27 7.11 HELENA CURTIS 29 7.12 N. SUE BARNES 30 7.13 ADRIANA SCHNEK 30 8. DISE?O METODOL?GICO 31 8.1 TIPO DE INVESTIGACI?N 31 8.2 FASES DE LA INVESTIGACI?N 32 8.3 POBLACI?N 33 8.4 MUESTRA 33 8.5 CATEGOR?AS 33 8.6 INSTRUMENTOS PARA LA RECOLECCI?N DE INFORMACI?N 33 8.6.1 Observaci?n participativa 34 8.6.2 Taller 34 9. CRONOGRAMA DE ACTIVIDADES 35 10. AN?LISIS DE RESULTADOS 36 10.1 PRE-T?S TALLER DE DIAGN?STICO 36 10.2 POST-TEST. PRUEBA FINAL 37 10.3 AN?LISIS COMPARATIVO 39 10.3.1 Diferencias de la c?lula animal y la c?lula vegetal 39 10.3.2 Funciones de la c?lula animal y vegetal 39 11. CONCLUSIONES 41 RECOMENDACIONES 42 REFERENCIAS 43 ANEXOS 4

Functional evaluation of constructed pseudo-endogenous microRNA-targeted myocardial ultrasound nanobubble

BackgroundStem cell transplantation is one of the treatment methods for acute myocardial infarction (AMI). MicroRNA-1 contributes to the study of the essential mechanisms of stem cell transplantation for treating AMI by targeted regulating the myocardial microenvironment after stem cell transplantation at the post-transcriptional level. Thus, microRNA-1 participates in regulating the myocardial microenvironment after stem cell transplantation, a promising strategy for the Stem cell transplantation treatment of AMI. However, the naked microRNA-1 synthesized is extremely unstable and non-targeting, which can be rapidly degraded by circulating RNase. Herein, to safely and effectively targeted transport the naked microRNA-1 synthesized into myocardial tissue, we will construct pseudo-endogenous microRNA-targeted myocardial ultrasound nanobubble pAd-AAV-9/miRNA-1 NB and evaluate its characteristics, targeting, and function.MethodsThe pAd-AAV-9/miRNA-1 gene complex was linked to nanobubble NBs by the “avidin-biotin bridging” method to prepare cardiomyocyte-targeted nanobubble pAd-AAV-9/miRNA-1 NB. The shape, particle size, dispersion, and stability of nanobubbles and the connection of pAd-AAV-9/miRNA-1 gene complex to nanobubble NB were observed. The virus loading efficiency was determined, and the myocardium-targeting imaging ability was evaluated using contrast-enhanced ultrasound imaging in vivo. The miRNA-1 expression level in myocardial tissue and other vital organs ex vivo of SD rats was considered by Q-PCR. Also, the cytotoxic effects were assessed.ResultsThe particle size of NBs was 504.02 ± 36.94 nm, and that of pAd-AAV-9/miRNA-1 NB was 568.00 ± 37.39 nm. The particle size and concentration of pAd-AAV-9/miRNA-1 NBs did not change significantly within 1 h at room temperature (p > 0.05). pAd-AAV-9/miRNA-1 NB had the highest viral load rate of 86.3 ± 2.2% (p < 0.05), and the optimum viral load was 5 μL (p < 0.05). pAd-AAV-9/miRNA-1 NB had good contrast-enhanced ultrasound imaging in vivo. Quantitative analysis of miRNA-1 expression levels in vital organs ex vivo of SD rats by Q-PCR showed that pAd-AAV-9/miRNA-1 NB targeted the myocardial tissue. Q-PCR indicated that the expression level of miRNA-1 in the myocardium of the pAd-AAV-9/miRNA-1 NB + UTMD group was significantly higher than that of the pAd-AAV-9/miRNA-1 NB group (p < 0.05). pAd-AAV-9/miRNA-1 NB had no cytotoxic effect on cardiomyocytes (p > 0.05).ConclusionThe pAd-AAV-9/miRNA-1 NB constructed in this study could carry naked miRNA-1 synthesized in vitro for targeted transport into myocardial tissue successfully and had sound contrast-enhanced imaging effects in vivo

Raw Garlic Consumption and Risk of Liver Cancer: A Population-Based Case-Control Study in Eastern China.

Although the major risk factors for liver cancer have been established, preventive factors for liver cancer have not been fully explored. We evaluated the association between raw garlic consumption and liver cancer in a large population-based case-control study in Eastern China. The study was conducted in Jiangsu, China, from 2003 to 2010. A total of 2011 incident liver cancer cases and 7933 randomly selected population-controls were interviewed. Epidemiological data including raw garlic intake and other exposures were collected, and serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection were assayed. Overall, eating raw garlic twice or more per week was inversely associated with liver cancer, with an adjusted odds ratio (aOR) of 0.77 (95% confidence interval (CI): 0.62-0.96) compared to those ingesting no raw garlic or less than twice per week. In stratified analyses, high intake of raw garlic was inversely associated with liver cancer among Hepatitis B surface antigen (HBsAg) negative individuals, frequent alcohol drinkers, those having history of eating mold-contaminated food or drinking raw water, and those without family history of liver cancer. Marginal interactions on an additive scale were observed between low raw garlic intake and HBsAg positivity (attributable proportion due to interaction (AP) = 0.31, 95% CI: -0.01-0.62) and heavy alcohol drinking (AP = 0.28, 95% CI: 0.00-0.57). Raw garlic consumption is inversely associated with liver cancer. Such an association shed some light on the potential etiologic role of garlic intake on liver cancer, which in turn might provide a possible dietary intervention to reduce liver cancer in Chinese population

Positive Relationship between Total Antioxidant Status and Chemokines Observed in Adults

Objective. Human evidence is limited regarding the interaction between oxidative stress biomarkers and chemokines, especially in a population of adults without overt clinical disease. The current study aims to examine the possible relationships of antioxidant and lipid peroxidation markers with several chemokines in adults. Methods. We assessed cross-sectional associations of total antioxidant status (TAS) and two lipid peroxidation markers malondialdehyde (MDA) and thiobarbituric acid reactive substances (TBARS) with a suite of serum chemokines, including CXCL-1 (GRO-α), CXCL-8 (IL-8), CXCL-10 (IP-10), CCL-2 (MCP-1), CCL-5 (RANTES), CCL-8 (MCP-2), CCL-11 (Eotaxin-1), and CCL-17 (TARC), among 104 Chinese adults without serious preexisting clinical conditions in Beijing before 2008 Olympics. Results. TAS showed significantly positive correlations with MCP-1 (r=0.15751, P=0.0014), MCP-2 (r=0.3721, P=0.0001), Eotaxin-1 (r=0.39598, P<0.0001), and TARC (r=0.27149, P=0.0053). The positive correlations remained unchanged after controlling for age, sex, body mass index, smoking, and alcohol drinking status. No associations were found between any of the chemokines measured in this study and MDA or TBARS. Similar patterns were observed when the analyses were limited to nonsmokers. Conclusion. Total antioxidant status is positively associated with several chemokines in this adult population