BackgroundDecidualization of the human endometrium, which involves a dramatic morphological and functional differentiation of human endometrial stromal cells (ESCs), is essential for the establishment of a successful pregnancy. Decidualization results from a complex interplay of transcription factors, morphogens, cytokines, cell cycle regulators, and signaling pathways.MethodsBased on a literature review, the regulation of, and the molecular mechanisms involved in, the decidualization of the endometrium are described.Main findingsProgesterone, together with proteins that are regulated by progesterone and/or cyclic adenosine monophosphate, including homeobox A10, forkhead box O1, signal transducers and activators of transcription, and heart and neural crest derivatives expressed transcript 2, forms a critical network for ESC decidualization and is a prerequisite to successful implantation. Decidualized ESCs contribute to the microenvironment at the feto–maternal interface and its direct or indirect influence on extracellular matrix remodeling, regulation of the local immune response, anti‐oxidative stress, and angiogenesis (vascular maturation). Impairment of this process is associated with a variety of pregnancy disorders, including infertility, recurrent miscarriages, and uteroplacental disorders.ConclusionA deeper understanding of the process of decidualization is expected to provide new insights into the fields of reproductive biology and reproductive medicine.

The biofilm of Pseudomonas aeruginosa could be removed by Varidase (streptodornase) that was used as defibrinating drug. After cultivating the biofilm on a silicone chip in a modified alginate-producing medium in vitro, it was treated with Varidase or DNase I. In both treatments, the biofilm was removed depending on the concentration of the reagents. Varidase was apparently effective under the condition that the biofilm was exposed to more than 625 U/ml (a quarter of the concentration of the medical use) for 3 h, twice, at 37°C. The result of this experiment indicates that (a) the DNases, DNase I and Varidase, were effective in destroying the biofilm of P. aeruginosa in vitro, and (b) in a clinical field, Varidase could be useful for P. aeruginosa focal infection, such as urinary tract infection, by removing the biofilm.

Cyclic changes of the human endometrium, such as proliferation, secretion, and decidualization, occur during regular menstrual cycles. Heart– and neural crest derivatives–expressed transcript 2 (HAND2) is a key transcription factor in progestin-induced decidualization of human endometrial stromal cells (ESCs). It has been suggested that HAND2 regulates interleukin 15 (IL15), a key immune factor required for the activation and survival of uterine natural killer (uNK) cells. Activated uNK cells can promote spiral artery remodeling and secrete cytokines to induce immunotolerance. To date, no studies have evaluated the transcription factors that regulate IL15 expression in human ESCs. In the present study, we examined whether HAND2 controls IL15 transcriptional regulation in human ESCs. Quantitative RT-PCR and histological analyses revealed that HAND2 and IL15 levels increase considerably in the secretory phase of human endometrium tissues. Results from ChIP-quantitative PCR suggested that HAND2 binds to a putative HAND2 motif, which we identified in the upstream region of the human IL15 gene through in silico analysis. Using a luciferase reporter assay, we found that the upstream region of the human IL15 gene up-regulates reporter gene activities in response to estradiol and a progestin representative (medroxyprogesterone) in ESCs. The upstream region of the human IL15 gene also exhibited increasing responsiveness to transfection with a HAND2 expression vector. Of note, deletion and substitution variants of the putative HAND2 motif in the upstream region of IL15 did not respond to HAND2 transfection. These findings confirm that HAND2 directly up-regulates human IL15 transcription in ESCs.

Objective: In Japan, the possible adverse events upon HPV vaccination was widely reported in the media. MHLW announced the suspension of aggressively encouraging HPV vaccination in 2013, and inoculation rate has sharply declined. The aim of the present study was estimation of future cervical cancer risk.Methods: The latest data on vaccination rate at each age in Sakai City were first investigated. The rate of experiencing sexual intercourse at the age of 12, 13, 14, 15, 16, 17 and throughout lifetime is assumed to be 0%, 1%, 2%, 5%, 15%, 25%, and 85% respectively. The cervical cancer risk was regarded to be proportional to the relative risk of HPV infection over the lifetime. The risk in those born in 1993 whom HPV vaccination was not available yet for was defined to be 1.0000.Results: The cumulative vaccination rates were 65.8% in those born in 1994, 72.7% in 1995, 72.8% in 1996, 75.7% in 1997, 75.0% in 1998, 66.8% in 1999, 4.1% in 2000, 1.5% in 2001, 0.1% in 2002, and 0.1% in 2003. The relative cervical cancer risk in those born in 1994–1999 was reduced to 0.56–0.70, however, the rate in those born in 2000–2003 was 0.98–1.0, almost the same risk as before introduction of the vaccine.Discussion: The cumulative initial vaccination rates were different by the year of birth. It is confirmed that the risk of future cervical cancer differs in accordance with the year of birth. For these females, cervical cancer screening should be recommended more strongly.

Our results should help in understanding the need for a strong promotion of vaccine usage and cancer screening after future retraction of the recommendation suspension. This may apply to other countries with an unsatisfactory rate of HPV vaccination due to fears of adverse vaccine events.

The endometrium is necessary for implantation, complete development of the placenta, and a successful pregnancy. The endometrium undergoes repeated cycles of proliferation, decidualization (differentiation), and shedding during each menstrual cycle. The endometrium—including stromal, epithelial, vascular endothelial, and immune cells—is both functionally and morphologically altered in response to progesterone, causing changes in the number and types of immune cells. Immune cells make up half of the total number of endometrial cells during implantation and menstruation. Surprisingly, immune tolerant cells in the endometrium (uterine natural killer cells, T cells, and macrophages) have two conflicting functions: to protect the body by eliminating pathogenic microorganisms and other pathogens and to foster immunological change to tolerate the embryo during pregnancy. One of the key molecules involved in this control is the cytokine interleukin-15 (IL-15), which is secreted by endometrial stromal cells. Recently, it has been reported that IL-15 is directly regulated by the transcription factor heart- and neural crest derivatives-expressed protein 2 in endometrial stromal cells. In this review, we outline the significance of the endometrium and immune cell population during menstruation and early pregnancy and describe the factors involved in immune tolerance and their involvement in the establishment and maintenance of pregnancy.

A BS TRACT: Parkinson's disease, as well as other neurodegenerative disorders, are primarily characterized by pathological accumulation of proteins, inflammation, and neuron loss. Although there are some known genetic risk factors, most cases cannot be explained by genetics alone. Therefore, it is important to determine the environmental factors that confer risk and the mechanisms by which they act. Recent epidemiological studies have found that exposure to air pollution is associated with an increased risk for development of Parkinson's disease, although not all results are uniform. The variability between these studies is likely due to differences in what components of air pollution are measured, timing and methods used to determine exposures, and correction for other variables. There are several potential mechanisms by which air pollution could act to increase the risk for development of Parkinson's disease, including direct neuronal toxicity, induction of systemic inflammation leading to central nervous system inflammation, and alterations in gut physiology and the microbiome. Taken together, air pollution is an emerging risk factor in the development of Parkinson's disease. A number of potential mechanisms have been implicated by which it promotes neuropathology providing biological plausibility, and these mechanisms are likely relevant to the development of other neurodegenerative disorders such as Alzheimer's disease. This field is in its early stages, but a better understanding of how environmental exposures influence the pathogenesis of neurodegeneration is essential for reducing the incidence of disease and finding disease-modifying therapies.

Parkinson’s disease is a common neurodegenerative disorder leading to severe disability. The clinical features reflect progressive neuronal loss, especially involving the dopaminergic system. The causes of Parkinson’s disease are slowly being uncovered and include both genetic and environmental insults. Zebrafish have been a valuable tool in modeling various aspects of human disease. Here, we review studies utilizing zebrafish to investigate both genetic and toxin causes of Parkinson’s disease. They have provided important insights into disease mechanisms and will be of great value in the search for disease-modifying therapies.