A simple biomechanical test with real-time displacement and strain mapping is reported, which provides displacement vectors and principal strain directions during the mechanical characterization of heart valve tissues. The maps reported in the current study allow us to quickly identify the approximate strain imposed on a location in the samples. The biomechanical results show that the aortic valves exhibit stronger anisotropic mechanical behavior than that of the pulmonary valves before 18% strain equibiaxial stretching. In contrast, the pulmonary valves exhibit stronger anisotropic mechanical behavior than aortic valves beyond 28% strain equibiaxial stretching. Simple biochemical tests are also conducted. Collagens are extracted at different time points (24, 48, 72, and 120 h) at different locations in the samples. The results show that extraction time plays an important role in determining collagen concentration, in which a minimum of 72 h of extraction is required to obtain saturated collagen concentration. This work provides an easy approach for quantifying biomechanical and biochemical properties of semilunar heart valve tissues, and potentially facilitates the development of tissue engineered heart valves.
It is well documented that the tumor microenvironment profoundly impacts the etiology and progression of breast cancer, yet the contribution of the resident microbiome within breast tissue remains poorly understood. Tumor microenvironmental conditions, such as hypoxia and dense tumor stroma, predispose progressive phenotypes and therapy resistance, however the role of bacteria in this interplay remains uncharacterized. We hypothesized that the effect of individual bacterial secreted molecules on breast cancer viability and proliferation would be modulated by these tumor-relevant stressors differentially for cells at varying stages of progression. To test this, we incubated human breast adenocarcinoma cells (MDA-MB-231, MCF-DCIS.com) and non-malignant breast epithelial cells (MCF-10A) with N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL), a quorum-sensing molecule from Pseudomonas aeruginosa that regulates bacterial stress responses. This molecule was selected because Pseudomonas was recently characterized as a significant fraction of the breast tissue microbiome and OdDHL is documented to impact mammalian cell viability. After OdDHL treatment, we demonstrated the greatest decrease in viability with the more malignant MDA-MB-231 cells and an intermediate MCF-DCIS.com (ductal carcinoma in situ) response. The responses were also culture condition (i.e. microenvironment) dependent. These results contrast the MCF-10A response, which demonstrated no change in viability in any culture condition. We further determined that the observed trends in breast cancer viability were due to modulation of proliferation for both cell types, as well as the induction of necrosis for MDA-MB-231 cells in all conditions. Our results provide evidence that bacterial quorum-sensing molecules interact with the host tissue environment to modulate breast cancer viability and proliferation, and that the effect of OdDHL is dependent on both cell type as well as microenvironment. Understanding the interactions between bacterial signaling molecules and the host tissue environment will allow for future studies that determine the contribution of bacteria to the onset, progression, and therapy response of breast cancer.
23 24 the breast tissue microbiome and OdDHL is documented to have significant effects on 36 mammalian cells. We found differences in the MDA-MB-231 and MCF-DCIS.com viability 37 after OdDHL treatment that were cell type and culture condition (i.e. microenvironment) 38 dependent. This result was in contrast to the MCF-10A cells, which demonstrated no change in 39 viability over the OdDHL concentration range examined, in any culture condition. We further 40 determined that the observed trends in breast cancer viability were due to modulation of 41 proliferation for both cell types, as well as the induction of necrosis for MDA-MB-231 cells in 42 all conditions. Our results provide evidence that bacterial quorum-sensing molecules interact 43 with the host environment to modulate breast cancer viability and proliferation, and that the 44 effect of OdDHL is dependent on both cell type as well as microenvironment. Understanding the 45 interactions between bacterial signaling molecules and the host tissue environment will allow for 46 3 future studies that determine the contribution of bacteria to the onset, progression, and therapy 47 response of breast cancer. 48 49 Introduction The tumor microenvironment is now a widely recognized and well-studied 50 contributor to cancer dynamics, particularly for breast cancer. While increased matrix density, 51 programming of cancer-associated stromal cells, evolving gradients of oxygen and nutrients, and 52 leaky vasculature have all been implicated as key players in breast cancer progression (1-4), the 53 impact of the recently identified breast tissue resident microbiotic niche has received little 54 attention. Beyond the effects of pathogenic or tumorigenic bacteria such as Chlamydophila 55 pneumonia, Salmonella typhi, Streptococcus gallolyticus (5), Helicobacter pylori (6) and 56 Fusobacterium nucleatum (7), the majority of analyses of tumor-microbiome interactions have 57 centered on local cell-cell interactions within the gut microenvironment, or more systemic 58 immune effects influenced by gut microbiota (8). Only a handful of studies have been conducted 59 to investigate the influences of tissue-resident bacteria in other tumor sites, such as for breast 60 cancer (9-11). Even fewer have investigated how small molecules released from resident bacteria 61 may interact with cells in the presence of other critical microenvironmental factors, e.g. tumor 62 hypoxia, to regulate cancer progression. In an effort to address these questions, we investigated 63 interactions between the quorum-sensing molecule N-(3-oxododecanoyl)-L-homoserine lactone 64 (OdDHL) and the breast tumor relevant microenvironmental cues of a stiff collagen-derived 65 tissue mimic and hypoxia. This representative study will aid in our understanding of how the 66 understudied breast tissue microbiome may contribute to disease phenotypes, patient-to-patient 67 variability, and cancer progression. 68 69 131 For 2D experimental conditions, cells were seeded in 48-well polystyrene plates at a 132 concentration ...
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