Evidence of two distinct functionally specialized fibroblast lineages in breast stroma

BACKGROUND: The terminal duct lobular unit (TDLU) is the most dynamic structure in the human breast and the putative site of origin of human breast cancer. Although stromal cells contribute to a specialized microenvironment in many organs, this component remains largely understudied in the human breast. We here demonstrate the impact on epithelium of two lineages of breast stromal fibroblasts, one of which accumulates in the TDLU while the other resides outside the TDLU in the interlobular stroma. METHODS: The two lineages are prospectively isolated by fluorescence activated cell sorting (FACS) based on different expression levels of CD105 and CD26. The characteristics of the two fibroblast lineages are assessed by immunocytochemical staining and gene expression analysis. The differentiation capacity of the two fibroblast populations is determined by exposure to specific differentiating conditions followed by analysis of adipogenic and osteogenic differentiation. To test whether the two fibroblast lineages are functionally imprinted by their site of origin, single cell sorted CD271(low)/MUC1(high) normal breast luminal epithelial cells are plated on fibroblast feeders for the observation of morphological development. Epithelial structure formation and polarization is shown by immunofluorescence and digitalized quantification of immunoperoxidase-stained cultures. RESULTS: Lobular fibroblasts are CD105(high)/CD26(low) while interlobular fibroblasts are CD105(low)/CD26(high). Once isolated the two lineages remain phenotypically stable and functionally distinct in culture. Lobular fibroblasts have properties in common with bone marrow derived mesenchymal stem cells and they specifically convey growth and branching morphogenesis of epithelial progenitors. CONCLUSIONS: Two distinct functionally specialized fibroblast lineages exist in the normal human breast, of which the lobular fibroblasts have properties in common with mesenchymal stem cells and support epithelial growth and morphogenesis. We propose that lobular fibroblasts constitute a specialized microenvironment for human breast luminal epithelial progenitors, i.e. the putative precursors of breast cancer. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-016-0769-2) contains supplementary material, which is available to authorized users

Investigating PM2.5 toxicity in highly polluted urban and industrial areas in the Middle East: human health risk assessment and spatial distribution

Abstract Exposure to particulate matter (PM) can be considered as a factor affecting human health. The aim of this study was to investigate the concentration of PM2.5 and heavy metals and their influence on survival of A549 human lung cells in exposure to PM2.5 breathing air of Ahvaz city. In order to assess the levels of PM2.5 and heavy metals, air samples were collected from 14 sampling stations positioned across Ahvaz city during both winter and summer seasons. The concentration of heavy metals was determined using ICP OES. Next, the MTT assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] was employed to ascertain the survival rate of A549 cells. The findings from this research demonstrated that average PM2.5 of the study period was (149.5 μg/m3). Also, the average concentration of PM2.5 in the urban area in winter and summer was (153.3- and 106.9 μg/m3) and in the industrial area this parameter was (191.6 and 158.3 μg/m3). The average concentration of metals (ng/m3) of urban areas against industrial, Al (493 vs. 485), Fe (536 vs. 612), Cu (198 vs. 212), Ni (128 vs. 129), Cr (48.5 vs. 54), Cd (118 vs. 124), Mn (120 vs. 119), As (51 vs. 67), Hg (37 vs. 50), Zn (302 vs. 332) and Pb (266 vs. 351) were obtained. The results of the MTT assay showed that the highest percentage of cell survival according to the exposure concentration was 25 > 50 > 100 > 200. Also, the lowest percentage of survival (58.8%) was observed in the winter season and in industrial areas with a concentration of 200 μg/ml. The carcinogenic risk assessment of heavy metals indicated that except for Cr, whose carcinogenicity was 1.32E−03, other metals were in the safe range (10–4–10–6) for human health. The high concentration of PM2.5 and heavy metals can increase respiratory and cardiovascular diseases and reduce the public health level of Ahvaz citizens

Metal organic framework-based photocatalyst-assisted peroxone process for formaldehyde and acetaldehyde removal from waste air stream: intermediates and mineralization

Formaldehyde (FA) and acetaldehyde (AA) are known as the two major pollutants used at industrial processes. The BiOI@NH2-MIL-125 (Ti)@Zeolite heterostructures combined with UV-assisted peroxone process were investigated for oxidative degradation of the aldehydes in a continuous waste air stream. Different characterisation methods including XRD, FTIR, FESEM, EDS, EDS elemental mapping, BET, TEM and XPS were used to characterise the photocatalyst. This study focuses on optimising the parameters selected for removal of FA and AA using the one-factor-at-a-time (OFAT) technique. Therefore, the effects of operational parameters: air flow rate, ozone feeding rate, hydrogen peroxide (H2O2) concentration, relative humidity (RH), and initial concentrations on FA and AA removal efficiency were investigated and optimised using the OFAT procedure. The results showed the complete degradation of FA and AA were achieved at optimal conditions (air flow rate: 0.2 L/min, O3 dosage: 0.3 and 0.4 mg/min for FA and AA, respectively, H2O2 concentration: 150 and 200 ppm for FA and AA, respectively, RH of 35%, and an initial pollutant concentration of 5 ppm). In addition, kinetic models revealed that the FA and AA degradation process are fitted with first-order kinetic (R2 = 0.85). Mineralisation analysis revealed that the complete degradation of FA and AA were obtained at CO2 levels of 4.3 and 3.9 ppm, respectively. Overall, it could be concluded that the suggested treatment method has the capability to efficiently eliminate the aldehydes of interest from waste gases.</p

Burden of mortality attributed to PM2.5 exposure in cities of Iran; contribution of short-term pollution peaks

The objective of this study was to determine the population exposure to PM2.5, and to quantify the effect of eliminating short-term pollution peaks on the number of cause-specific deaths, the number of years of life lost (YLL), and economic losses attributed to exposure to PM2.5 in 25 Iranian cities with available air quality data. Number of deaths and YLL were estimated with AirQ + software tool using available concentration-response functions and life table approach. Furthermore, the value of lost life in each city were calculated using the Value of Statistical Life (VSL) method. Two scenarios were defined; Scenario A, considering actual observed concentrations to estimate the real health effects of PM2.5, and Scenario B, controlling for the effect of air pollution episodes. The results showed that the annual average concentrations of PM2.5 in cities were 1.5–6.1 times higher than the guideline value of WHO (10 μg/m³). The total number of all-cause deaths due to long-term exposure exceeding WHO air quality guideline level was 13321 (95% C.I.: 8837–17378) cases per year in all cities. The total numbers of chronic obstructive pulmonary disease (COPD), lung cancer, ischemic heart disease (IHD), and stroke deaths attributed to the exposure were 274, 315, 1536, and 963 cases, respectively. The total number of YLL over 10 years period in all 25 cities was 486,289 years and the loss of life expectancy ranged from 0.43 to 1.87 years. The sum of economic losses due to lost life exceeded 5.8 billion USD. Except for some cities, avoiding highly polluted days in Scenario B would result in only 5% reduction in overall health or economic effects. These results indicate an urgent need for new comprehensive plans to tackle air pollution in Iranian cities focused on reduction of long term average pollution levels since programs for avoiding highly polluted days lead to a limited health benefits only.The authors wish to thank Shahid Beheshti University of Medical Sciences (grant number #20330). We thank the Environmental and Occupational Health Centre of the Ministry of Health and Medical Education for providing data.Peer reviewe