Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib,Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment

The CDK4/6 inhibitors (CDKi) palbociclib, ribociclib, and abemaciclib are currently approved in combination with anti-estrogen therapy for the treatment of advanced and/or metastatic hormone receptor-positive/HER2-neu-negative breast cancer patients. Given the high incidence of bone metastases in this population, we investigated and compared the potential effects of palbociclib, ribociclib, and abemaciclib on the breast cancer bone microenvironment. Primary osteoclasts (OCs) and osteoblasts (OBs) were obtained from human monocyte and mesenchymal stem cells, respectively. OC function was evaluated by tartrate-resistant acid phosphatase assay and real-time PCR; OB activity was assessed by an alizarin red assay. OB/breast cancer co-culture models were generated via the seeding of MCF-7 cells on a layer of OBs, and tumor cell proliferation was analyzed using flow cytometry. Here, we showed that ribociclib, palbociclib, and abemaciclib exerted similar inhibitory effects on the OC differentiation and expression of bone resorption markers without affecting OC viability. On the other hand, the three CDKi did not affect the ability of OB to produce bone matrix, even if the higher doses of palbociclib and abemaciclib reduced the OB viability. In OB/MCF-7 co-culture models, palbociclib demonstrated a lower anti-tumor effect than ribociclib and abemaciclib. Overall, our results revealed the direct effects of CDKi on the tumor bone microenvironment, highlighting differences potentially relevant for clinical practice.     

Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth

Connexin37 (Cx37) and Cx40 form intercellular channels between endothelial cells (EC), which contribute to the regulation of the functions of vessels. We previously documented the participation of both Cx in developmental angiogenesis and have further shown that loss of Cx40 decreases the growth of different tumors. Here, we report that loss of Cx37 reduces (1) the in vitro proliferation of primary human EC; (2) the vascularization of subcutaneously implanted matrigel plugs in Cx37−/− mice or in WT using matrigel plugs supplemented with a peptide targeting Cx37 channels; (3) tumor angiogenesis; and (4) the growth of TC-1 and B16 tumors, resulting in a longer mice survival. We further document that Cx37 and Cx40 function in a collaborative manner to promote tumor growth, inasmuch as the injection of a peptide targeting Cx40 into Cx37−/− mice decreased the growth of TC-1 tumors to a larger extent than after loss of Cx37. This loss did not alter vessel perfusion, mural cells coverage and tumor hypoxia compared to tumors grown in WT mice. The data show that Cx37 is relevant for the control of EC proliferation and growth in different tumor models, suggesting that it may be a target, alone or in combination with Cx40, in the development of anti-tumoral treatments.     

MicroRNA Cross-Involvement in Acne Vulgaris and Hidradenitis Suppurativa: A Literature Review

Acne Vulgaris (AV) and Hidradenitis suppurativa (HS) are common chronic inflammatory skin conditions that affect the follicular units that often coexist or are involved in differential diagnoses. Inflammation in both these diseases may result from shared pathways, which may partially explain their frequent coexistence. MicroRNAs (miRNAs) are a class of endogenous, short, non-protein coding, gene-silencing or promoting RNAs that may promote various inflammatory diseases. This narrative review investigates the current knowledge regarding miRNAs and their link to AV and HS. The aim is to examine the role of these molecules in the pathogenesis of AV and HS and to identify possible common miRNAs that could explain the similar characteristics of these two diseases. Five miRNA (miR-155 miR-223-, miR-21, and miRNA-146a) levels were found to be altered in both HS and AV. These miRNAs are related to pathogenetic aspects common to both pathologies, such as the regulation of the innate immune response, regulation of the Th1/Th17 axis, and fibrosis processes that induce scar formation. This review provides a starting point for further studies aimed at investigating the role of miRNAs in AV and HS for their possible use as diagnostic-therapeutic targets.     

An automatic procedure for the synthesis and optimization of very low-frequency Gm–C integrators

Fully integrated low frequency filters are critical cells that should be carefully designed in order to avoid excessive area occupation. In this work we propose an automatic procedure capable of optimizing the design of G_m?CC integrators, which constitute the basis of a wide class of G_m?CC filters. The optimization target is minimizing the cell area with constraints on input range and low frequency noise. Lower and upper bounds can be fixed to most quantities and design parameters in order to avoid solutions that are not compatible with the physical limitations of the process. The program has been developed within the MATLAB^? platform, exploiting the optimization toolbox. The effect of several important design parameters on the optimization of low frequency integrators has been investigated using the proposed routine. The strong interaction between noise and low frequency constraints has been demonstrated, showing the impressive impact of strict noise specifications on the occupied area. The actual effectiveness of parameters such as the current division factor or approaches such as flicker noise rejection by means of chopper modulation has been investigated. Examples of integrator synthesis, performed using the proposed procedure configured with the parameters of a commercial CMOS process, are presented. The consistence between the characteristics of the cells and the initial specifications has been checked using electrical simulations showing a maximum discrepancy with the initial specifications of nearly 80%. A semi-manual method to refine the synthesized cells and improve the accuracy is proposed.     

A systematic method for predetermined scanning electron microscope analysis in dental science

Scanning electron microscope evaluation could be criticized if the method adopted to correct for bias is not specified in the study design. Observers can draw conclusions from images unconsciously chosen to best support their research hypotheses, impairing the basic research principle of operator's impartiality. In this study, a systematic observation method has been described and verified for repeatability. The number and the observation points on a certain specimen have been predetermined using a scheme along with observation rules previously established in the research protocol. When our instrument is used at an operating magnification between 500× and 1,000× (corresponding to a frame of 250×190 µ and 120×90 µ, respectively), the method allowed 100% repeatable observation frames, with linear frame errors in finding an observation point of 12.5% in length and 16.8% in height. With modifications to accommodate research objective and statistical requirements, the method could be applied to many SEM observation study. SCANNING 32: 97–103, 2010. © 2010 Wiley Periodicals, Inc.     

Personal multimedia services over a common home and access networking environment

This article presents a new end-to-end architecture model that will enable the deployment of a plethora of different multimedia services from diverse suppliers competitively coexisting over a common access and home networking environment. The model is focused on personal multimedia communication services and terminals. The proposed model is a segmentation of the end-to-end multimedia chain into several business segments. The interfaces among segments and functional entities inside each segment are identified and defined in the work. In order to study the impact level of the results achieved, a comparison with the approximation to NGN provided by current standardization bodies in the field (3GPP and TISPAN) is also included in the article. This comparison highlights the advantages of using this model as a solution to offer PMC services.     

Recovery of anthocyanins from eggplant peel

Tartaric and malic acid solutions were tested to extract anthocyanins from eggplant peel by a discontinuous process to obtain a natural red colorant. Extraction optimization was carried out, using different solvents, acid concentration, temperature, time of extraction and solvent-to-solid ratio as independent variables. Tartaric acid was more efficient than malic acid in both extraction yield and rate. Comparative tests were carried out using acidified ethanol as solvent. Delphinidin-3-rutinoside was extracted and identified as the major anthocyanin in eggplant peel. Concentration of different extracts from eggplant peel was carried out using EXA-31, a methacrylic food grade resin, the best performing resin to obtain highly concentrated extracts.