Mammary adipocytes promote breast tumor cell invasion and angiogenesis in the context of menopause and obesity.

The mechanism(s) underlying obesity-related postmenopausal (PM) breast cancer (BC) are not clearly understood. We hypothesized that the increased local presence of 'obese' mammary adipocytes within the BC microenvironment promotes the acquisition of an invasive and angiogenic BC cell phenotype and accelerates tumor proliferation and progression. BC cells, treated with primary mammary adipocyte secretome from premenopausal (Pre-M) and PM obese women (ObAdCM; obese adipocyte conditioned-media) upregulated the expression of several pro-tumorigenic factors including VEGF, lipocalin-2 and IL-6. Both Pre-M and PM ObAdCM stimulated endothelial cell recruitment and proliferation and significantly stimulated BC cell proliferation, migration and invasion. IL-6 and LCN2 induced STAT3/Akt signaling in BC cells and STAT3 inhibition abrogated the ObAdCM-stimulated BC cell proliferation and migration. Expression of proangiogenic regulators including VEGF, NRP1, NRP2, IL8RB, TGFß2, and TSP-1 were found to be differentially regulated in mammary adipocytes from obese PM women. Comparative RNAseq indicated an upregulation of PI3K/Akt signaling, ECM-receptor interactions and lipid/fatty acid metabolism in PM versus Pre-M mammary adipocytes. Our results demonstrate that irrespective of menopausal status, cross-talk between obese mammary adipocytes and BC cells promotes tumor aggressiveness and suggest that targeting the LCN2/IL-6/STAT3 signaling axis may be a useful strategy in obesity-driven breast tumorigenesis.

Identification and Characterization of Human Breast Milk and Infant Fecal Cultivable Lactobacilli Isolated in Bulgaria: A Pilot Study.

During the last few decades, the main focus of numerous studies has been on the human breast milk microbiota and its influence on the infant intestinal microbiota and overall health. The presence of lactic acid bacteria in breast milk affects both the quantitative and qualitative composition of the infant gut microbiota. The aim of this study was to assess the most frequently detected cultivable rod-shaped lactobacilli, specific for breast milk of healthy Bulgarian women and fecal samples of their infants over the first month of life, in 14 mother-infant tandem pairs. Additionally, we evaluated the strain diversity among the most common isolated species. A total of 68 Gram-positive and catalase-negative strains were subjected to identification using the MALDI-TOF technique. Predominant cultivable populations belonging to the rod-shaped lactic acid bacteria have been identified as Lacticaseibacillus rhamnosus, Limosilactobacillus fermentum, Lacticaseibacillus paracasei, and Limosilactobacillus reuteri. Also, we confirmed the presence of Lactiplantibacillus plantarum and Lactobacillus gasseri. Up to 26 isolates were selected as representatives and analyzed by 16S rRNA sequencing for strain identity confirmation and a phylogenetic tree based on 16S rRNA gene sequence was constructed. Comparative analysis by four RAPD primers revealed genetic differences between newly isolated predominant L. rhamnosus strains. This pilot study provides data for the current first report concerning the investigation of the characteristic cultivable lactobacilli isolated from human breast milk and infant feces in Bulgaria.

Host-guest complexation of cucurbit[7]uril and cucurbit[8]uril with the antimuscarinic drugs tropicamide and atropine.

Cucurbiturils are useful excipients in eye drop formulations: they can increase the water solubility of the drug, enhance drug absorption into the eye, improve aqueous stability and reduce local irritation. Effective and safe drug delivery is, however, a challenge and the information on the host (CBs)/guest (tropicamide and atropine) interactions can help improving the existing treatments and develop novel therapies not limited only to eye diseases/conditions. Since this carrier system can easily modify the properties of the drug and ensure its delivery at the targeted ocular tissue, further insight into the intimate mechanism of the host-guest recognition is crucial. The present DFT/SMD study focuses on the role of numerous factors governing this process, namely the specific position of the guest molecule in the cavity of the cucurbituril, the ionization form (non/protonated) of the antimuscarinic drug, the dielectric constant of the medium, and the size of the cavitant pore. The obtained results are in line with experimental observations and shed light on the mechanism, at atomic resolution, of recognition between the CBs and the two parasympatholytic drugs.