The traditional Mediterranean diet (MD) is associated with long life and lower prevalence of cardiovascular disease and cancers. The main components of this diet include high intake of fruit, vegetables, red wine, extra virgin olive oil (EVOO) and fish, low intake of dairy and red meat. Olive oil has gained support as a key effector of health benefits and there is evidence that this relates to the polyphenol content. Olive leaf extract (OLE) contains a higher quantity and variety of polyphenols than those found in EVOO. There are also important structural differences between polyphenols from olive leaf and those from olive fruit that may improve the capacity of OLE to enhance health outcomes. Olive polyphenols have been claimed to play an important protective role in cancer and other inflammation-related diseases. Both inflammatory and cancer cell models have shown that olive leaf polyphenols are anti-inflammatory and protect against DNA damage initiated by free radicals. The various bioactive properties of olive leaf polyphenols are a plausible explanation for the inhibition of progression and development of cancers. The pathways and signaling cascades manipulated include the NF-κB inflammatory response and the oxidative stress response, but the effects of these bioactive components may also result from their action as a phytoestrogen. Due to the similar structure of the olive polyphenols to oestrogens, these have been hypothesized to interact with oestrogen receptors, thereby reducing the prevalence and progression of hormone related cancers. Evidence for the protective effect of olive polyphenols for cancer in humans remains anecdotal and clinical trials are required to substantiate these claims idea. This review aims to amalgamate the current literature regarding bioavailability and mechanisms involved in the potential anti-cancer action of olive leaf polyphenols.

Correct development of the placenta is critical to establishing pregnancy and inadequate placentation leads to implantation failure and miscarriage, as well as later gestation pregnancy disorders. Much attention has been focused on the placental trophoblasts and it is clear that the trophoblast lineages arise from the trophectoderm of the blastocyst. In contrast, the cells of the placental mesenchyme are thought to arise from the inner cell mass, but the details of this process are limited. Due to ethical constraints and the inaccessibility of very early implantation tissues, our knowledge of early placentation has been largely based on historical histological sections. More recently, stem cell technologies have begun to shed important new light on the origins of the placental mesenchymal lineages. This review aims to amalgamate the older and more modern literature regarding the origins of the non-trophoblast lineages of the human placenta. We highlight ways in which rapidly developing stem cell technologies may shed new light on these crucial peri-implantation events. Relevant articles were identified using the PubMed database and Google Scholar search engines. A pearl growing method was used to expand the scope of papers relevant to the cell differentiation events of non-trophoblast placental lineages. At the start of pregnancy, cells of the extraembyronic mesoderm migrate to underlie the primitive trophoblast layers forming the first placental villi. The mesenchymal cells in the villus core most likely originate from the hypoblast of the embryo, but whether cells from the epiblast also contribute is yet to be determined. This is important because, following the formation of the villus core, vasculogenesis and haematopoiesis take place in the nascent placenta before it is connected to the embryonic circulation, making it likely that haematopoietic foci, placental macrophages, endothelial cells and vascular smooth muscle cells all arise in the placenta de novo. Evidence from the stem cell field indicates that these cells could directly differentiate from the extraembryonic mesoderm. However, the lineage hierarchy involved in cell fate decisions has not been well-established. Mesodermal progenitors capable of differentiating into both vascular and haematopoietic lineages can be derived from human embryonic stem cells, but the identification of such stem cells in the placenta is lacking. Future work profiling rare progenitor populations in early placentae will aid our understanding of early placentation. Understanding the origins of the cell lineages of the normal placenta will help us understand why so many pregnancies fail and address mechanisms that may salvage some of these losses.

Olive leaf extract (OLE) has been used for many years for its putative health benefits, but, to date, scientific evidence for the basis of these effects has been weak. Although recent literature has described a link between ailments such as cardiovascular disease, diabetes and cancer and a protective effect of polyphenols in the OLE, the mode of action is still unclear. Here, we describe a double-blinded placebo (PBO)-controlled trial, in which gene expression profiles of peripheral blood mononuclear cells from healthy male volunteers (n = 29) were analysed to identify genes that responded to OLE, following an eight-week intervention with 20 mL daily consumption of either OLE or PBO. Differences between groups were determined using an adjusted linear model. Subsequent analyses indicated downregulation of genes important in inflammatory pathways, lipid metabolism and cancer as a result of OLE consumption. Gene expression was verified by real-time PCR for three genes (EGR1, COX-2 and ID3). The results presented here suggest that OLE consumption may result in health benefits through influencing the expression of genes in inflammatory and metabolic pathways. Future studies with a larger study group, including male and female participants, looking into direct effects of OLE on lipid metabolism and inflammation are warranted.

Single-cell technologies (RNA-sequencing, flow cytometry) are critical tools to reveal how cell heterogeneity impacts developmental pathways. The placenta is a fetal exchange organ, containing a heterogeneous mix of mesenchymal cells (fibroblasts, myofibroblasts, perivascular, and progenitor cells). Placental mesenchymal stromal cells (pMSC) are also routinely isolated, for therapeutic and research purposes. However, our understanding of the diverse phenotypes of placental mesenchymal lineages, and their relationships remain unclear. We designed a 23-colour flow cytometry panel to assess mesenchymal heterogeneity in first-trimester human placentae. Four distinct mesenchymal subsets were identified; CD73⁺CD90⁺ mesenchymal cells, CD146⁺CD271⁺ perivascular cells, podoplanin⁺CD36⁺ stromal cells, and CD26⁺CD90⁺ myofibroblasts. CD73⁺CD90⁺ and podoplanin + CD36+ cells expressed markers consistent with cultured pMSCs, and were explored further. Despite their distinct ex-vivo phenotype, in culture CD73⁺CD90⁺ cells and podoplanin⁺CD36⁺ cells underwent phenotypic convergence, losing CD271 or CD36 expression respectively, and homogenously exhibiting a basic MSC phenotype (CD73⁺CD90⁺CD31^-CD144^-CD45^-). However, some markers (CD26, CD146) were not impacted, or differentially impacted by culture in different populations. Comparisons of cultured phenotypes to pMSCs further suggested cultured pMSCs originate from podoplanin⁺CD36⁺ cells. This highlights the importance of detailed cell phenotyping to optimise therapeutic capacity, and ensure use of relevant cells in functional assays.