Microvesicles secreted by macrophages shuttle invasion-potentiating microRNAs into breast cancer cells

<p>Abstract</p> <p>Background</p> <p>Tumor-associated macrophages (TAMs) are alternatively activated cells induced by interleukin-4 (IL-4)-releasing CD4⁺T cells. TAMs promote breast cancer invasion and metastasis; however, the mechanisms underlying these interactions between macrophages and tumor cells that lead to cancer metastasis remain elusive. Previous studies have found microRNAs (miRNAs) circulating in the peripheral blood and have identified microvesicles, or exosomes, as mediators of cell-cell communication. Therefore, one alternative mechanism for the promotion of breast cancer cell invasion by TAMs may be through macrophage-secreted exosomes, which would deliver invasion-potentiating miRNAs to breast cancer cells.</p> <p>Results</p> <p>We utilized a co-culture system with IL-4-activated macrophages and breast cancer cells to verify that miRNAs are transported from macrophages to breast cancer cells. The shuttling of fluorescently-labeled exogenous miRNAs from IL-4-activated macrophages to co-cultivated breast cancer cells without direct cell-cell contact was observed. miR-223, a miRNA specific for IL-4-activated macrophages, was detected within the exosomes released by macrophages and was significantly elevated in the co-cultivated SKBR3 and MDA-MB-231 cells. The invasiveness of the co-cultivated breast cancer cells decreased when the IL-4-activated macrophages were treated with a miR-223 antisense oligonucleotide (ASO) that would inhibit miR-223 expression. Furthermore, results from a functional assay revealed that miR-223 promoted the invasion of breast cancer cells via the Mef2c-β-catenin pathway.</p> <p>Conclusions</p> <p>We conclude that macrophages regulate the invasiveness of breast cancer cells through exosome-mediated delivery of oncogenic miRNAs. Our data provide insight into the mechanisms underlying the metastasis-promoting interactions between macrophages and breast cancer cells.</p

Rapid and effective removal of copper, nitrate and trichloromethane from aqueous media by aluminium alloys

Zero-valent iron (ZVI) has been extensively studied for its efficacy in removing heavy metals, nitrate, and chlorinated organic compounds from contaminated water. However, its limited effectiveness due to rapid passivation and poor selectivity is prompting for alternative solutions, such as the use of aluminium alloys. In this study, the efficacy of five distinct aluminium alloys, namely Al–Mg, Al–Fe, Al–Cu, and Al–Ni, each comprising 50 % Al by mass at a concentration of 10 g/L, was assessed using copper, nitrate and trichloromethane (TCM) as model contaminants. Results show that chemical pollutants reacted immediately with Al–Mg. On the contrary, the remaining three alloys exhibited a delay of 24 h before demonstrating significant reactivity. Remarkably, Al–Mg alloy reduced nitrate exclusively to ammonium, indicating minimal preference for nitrate reduction to N2. In contrast, the Al–Cu, Al–Ni, and Al–Fe alloys exhibited N2 selectivity of 3 %, 5 %, and 19 %, respectively. The removal efficiency of copper, nitrate and TCM reached 99 % within 24 h, 95 % within 48h and 48 % within 48h, respectively. Noteworthy findings included the correlation between Fe concentration within the Al–Fe alloy and an increased N2 selectivity from 9.3 % to 24.1 %. This resulted in an increase of Fe concentration from 10 % to 58 % albeit with a concurrent reduction in reactivity. Cu2+ removal by Al–Fe alloy occurred via direct electron transfer, while the removal of nitrate and TCM was facilitated by atomic hydrogen generated by the alloy's hydrolysis. Intriguingly, nitrate and TCM suppressed Cu2+ reduction, whereas Cu2+ improved nitrate reduction and TCM degradation. These findings demonstrate the great potential of Al–Mg and Al–Fe alloys as highly efficient agents for water remediation

Effects of Casein, Chicken, and Pork Proteins on the Regulation of Body Fat and Blood Inflammatory Factors and Metabolite Patterns Are Largely Dependent on the Protein Level and Less Attributable to the Protein Source

The impact of meat protein on metabolic regulation is still disputed and may be influenced by protein level. This study aimed to explore the effects of casein, pork, and chicken proteins at different protein levels (40% E vs 20% E) on body weight regulation, body fat accumulation, serum hormone levels, and inflammatory factors/metabolites in rats maintained on high-fat (45% E fat) diets for 84 d. Increased protein levels resulted in a significant reduction in body fat mass and an increase in the serum levels of the anti-inflammatory cytokine IL-10, independent of protein source. Analysis of blood via untargeted metabolomics analysis identified eight, four, and four metabolites significantly altered by protein level, protein source, and a protein level-source interaction, respectively. Together, the effects of casein, chicken, and pork protein on the regulation of body fat accumulation and blood metabolite profile are largely dependent on protein level and less attributable to the protein source

Markers of Tumor-Initiating Cells Predict Chemoresistance in Breast Cancer

PURPOSE: Evidence is lacking whether the number of breast tumor-initiating cells (BT-ICs) directly correlates with the sensitivity of breast tumors to chemotherapy. Here, we evaluated the association between proportion of BT-ICs and chemoresistance of the tumors. METHODS: Immunohistochemical staining(IHC) was used to examine the expression of aldehyde dehydrogenase 1 (ALDH1) and proliferating cell nuclear antigen, and TUNEL was used to detect the apoptosis index. The significance of various variables in patient survival was analyzed using a Cox proportional hazards model. The percentage of BT-ICs in breast cancer cell lines and primary breast tumors was determined by ALDH1 enzymatic assay, CD44(+)/CD24(-) phenotype and mammosphere formation assay. RESULTS: ALDH1 expression determined by IHC in primary breast cancers was associated with poor clinical response to neoadjuvant chemotherapy and reduced survival in breast cancer patients. Breast tumors that contained higher proportion of BT-ICs with CD44(+)/CD24(-) phenotype, ALDH1 enzymatic activity and sphere forming capacity were more resistant to neoadjuvant chemotherapy. Chemoresistant cell lines AdrR/MCF-7 and SK-3rd, had increased number of cells with sphere forming capacity, CD44(+)/CD24(-) phenotype and side-population. Regardless the proportion of T-ICs, FACS-sorted CD44(+)/CD24(-) cells that derived from primary tumors or breast cancer lines were about 10-60 fold more resistant to chemotherapy relative to the non- CD44(+)/CD24(-) cells and their parental cells. Furthermore, our data demonstrated that MDR1 (multidrug resistance 1) and ABCG2 (ATP-binding cassette sub-family G member 2) were upregulated in CD44(+)/CD24(-) cells. Treatment with lapatinib or salinomycin reduced the proportion of BT-ICs by nearly 50 fold, and thus enhanced the sensitivity of breast cancer cells to chemotherapy by around 30 fold. CONCLUSIONS: These data suggest that the proportion of BT-ICs is associated with chemotherapeutic resistance of breast cancer. It highlights the importance of targeting T-ICs, rather than eliminating the bulk of rapidly dividing and terminally differentiated cells, in novel anti-cancer strategies

Rectangular Coordination Polymer Nanoplates: Large-Scale, Rapid Synthesis and Their Application as a Fluorescent Sensing Platform for DNA Detection

In this paper, we report on the large-scale, rapid synthesis of uniform rectangular coordination polymer nanoplates (RCPNs) assembled from Cu(II) and 4,4′-bipyridine for the first time. We further demonstrate that such RCPNs can be used as a very effective fluorescent sensing platform for multiple DNA detection with a detection limit as low as 30 pM and a high selectivity down to single-base mismatch. The DNA detection is accomplished by the following two steps: (1) RCPN binds dye-labeled single-stranded DNA (ssDNA) probe, which brings dye and RCPN into close proximity, leading to fluorescence quenching; (2) Specific hybridization of the probe with its target generates a double-stranded DNA (dsDNA) which detaches from RCPN, leading to fluorescence recovery. It suggests that this sensing system can well discriminate complementary and mismatched DNA sequences. The exact mechanism of fluorescence quenching involved is elucidated experimentally and its use in a human blood serum system is also demonstrated successfully

Poly(m-Phenylenediamine) Nanospheres and Nanorods: Selective Synthesis and Their Application for Multiplex Nucleic Acid Detection

In this paper, we demonstrate for the first time that poly(m-phenylenediamine) (PMPD) nanospheres and nanorods can be selectively synthesized via chemical oxidation polymerization of m-phenylenediamine (MPD) monomers using ammonium persulfate (APS) as an oxidant at room temperature. It suggests that the pH value plays a critical role in controlling the the morphology of the nanostructures and fast polymerization rate favors the anisotropic growth of PMPD under homogeneous nucleation condition. We further demonstrate that such PMPD nanostructures can be used as an effective fluorescent sensing platform for multiplex nucleic acid detection. A detection limit as low as 50 pM and a high selectivity down to single-base mismatch could be achieved. The fluorescence quenching is attributed to photoinduced electron transfer from nitrogen atom in PMPD to excited fluorophore. Most importantly, the successful use of this sensing platform in human blood serum system is also demonstrated

Double Burden of Malnutrition among Chinese Women of Reproductive Age and Their Social Determinants

This study aimed to examine the impact of a wide range of demographic, socioeconomic, and community factors on the double burden of malnutrition among women of reproductive age using longitudinal data. We used data about 11,348 women of reproductive age who participated in the China Health and Nutrition Survey (CHNS), a longitudinal survey, between 1989 and 2015. Nutritional outcomes were categorized into four groups, namely underweight, normal weight, overweight, and obesity, with normal weight as reference. A multinomial logit model was fitted due to geographic clustering and repeated observations of individuals. The prevalence of underweight decreased over time from 1991 but has tended to rise again since 2004, while the prevalence of overweight/obesity continued to rise between 1991 and 2015. Improved individual factors, socioeconomic status, and community urbanization reduced the risk of underweight but elevated the risk of overweight and obesity. The medium levels, rather than the highest levels, of household income and community urbanization are associated with a higher risk of overweight and obesity. The notable increase in underweight prevalence is a cause for concern to be addressed along with efforts to curb the rising tide of overweight. In order to enhance the nutritional status of women of reproductive age, it is essential to improving the community environment, levels of education, and living environment from a wider context. Long-term and targeted plans are urgently needed for nutrition improvements among the different populations

Drift-off warning limits for deepwater drilling platform/riser coupling system

The drift-off dynamic model of deepwater drilling platform and riser coupling system was established. An analysis method on drift-off warning limits of deepwater drilling platform and riser coupling system was proposed, and a deepwater drilling platform/riser system was taken for case study. The analysis model of deepwater riser, wellhead and conductor coupling system and the drift-off dynamic model of platform were established respectively. The drift-off dynamic solver of deepwater platform was developed. The coupling dynamic characteristics and coupling effect of the deepwater drilling platform and riser system were analyzed in combination with example, and the analysis method for drift-off warning limits was described. The results show that: the riser load acting on platform plays a driving role in the platform drift-off in the initial drift-off stage, and begins to inhibit the platform drift-off gradually as the drift-off displacement increases; During the platform drift-off, the transient response speed of upper riser parameters is high, while the transient response of lower riser parameters presents an obvious hysteresis effect; As the current speed increases or water depth decreases, the drift-off warning limits of deepwater drilling platform/riser coupling system decrease and the deepwater drilling riser should be disconnected earlier. Key words: deepwater drilling, drilling platform, riser, drift-off dynamic model, drift-off warning limit

Contextual Features and Information Bottleneck-Based Multi-Input Network for Breast Cancer Classification from Contrast-Enhanced Spectral Mammography

In computer-aided diagnosis methods for breast cancer, deep learning has been shown to be an effective method to distinguish whether lesions are present in tissues. However, traditional methods only classify masses as benign or malignant, according to their presence or absence, without considering the contextual features between them and their adjacent tissues. Furthermore, for contrast-enhanced spectral mammography, the existing studies have only performed feature extraction on a single image per breast. In this paper, we propose a multi-input deep learning network for automatic breast cancer classification. Specifically, we simultaneously input four images of each breast with different feature information into the network. Then, we processed the feature maps in both horizontal and vertical directions, preserving the pixel-level contextual information within the neighborhood of the tumor during the pooling operation. Furthermore, we designed a novel loss function according to the information bottleneck theory to optimize our multi-input network and ensure that the common information in the multiple input images could be fully utilized. Our experiments on 488 images (256 benign and 232 malignant images) from 122 patients show that the method&rsquo;s accuracy, precision, sensitivity, specificity, and f1-score values are 0.8806, 0.8803, 0.8810, 0.8801, and 0.8806, respectively. The qualitative, quantitative, and ablation experiment results show that our method significantly improves the accuracy of breast cancer classification and reduces the false positive rate of diagnosis. It can reduce misdiagnosis rates and unnecessary biopsies, helping doctors determine accurate clinical diagnoses of breast cancer from multiple CESM images