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The mammary gland is a hormone sensitive organ that is susceptible to endocrine-disrupting chemicals (EDCs) during the vulnerable periods of parous reorganization (ie, pregnancy, lactation, and involution). Pregnancy is believed to have long-term protective effects against breast cancer development; however, it is unknown if EDCs can alter this effect. We examined the long-term effects of propylparaben, a common preservative used in personal care products and foods, with estrogenic properties, on the parous mouse mammary gland. Pregnant BALB/c mice were treated with 0, 20, 100, or 10 000 µg/kg/day propylparaben throughout pregnancy and lactation. Unexposed nulliparous females were also evaluated. Five weeks post-involution, mammary glands were collected and assessed for changes in histomorphology, hormone receptor expression, immune cell number, and gene expression. For several parameters of mammary gland morphology, propylparaben reduced the effects of parity. Propylparaben also increased proliferation, but not stem cell number, and induced modest alterations to expression of ERα-mediated genes. Finally, propylparaben altered the effect of parity on the number of several immune cell types in the mammary gland. These results suggest that propylparaben, at levels relevant to human exposure, can interfere with the effects of parity on the mouse mammary gland and induce long-term alterations to mammary gland structure. Future studies should address if propylparaben exposures negate the protective effects of pregnancy on mammary cancer development.Studies of the geographic distribution of sand flies and the factors associated with their occurrence are necessary to understand the risk of leishmaniasis transmission. The objective of this study was to characterize the sand fly fauna, particularly the spatial distribution of Lutzomyia longipalpis (Lutz & Neiva), and correlate these with climate factors in the Dourados municipality, Brazil. The collection of sand flies was carried out with CDC Light Traps over two periods at six sites for three consecutive nights each month from August 2012 to July 2013; and at four other sites for two consecutive nights each month from April 2017 to February 2018. We collected 591 sand flies in the first period and 121 in the second period for a total of 712 sand flies; 697 of the total collected were Lu. longipalpis. The minimum and maximum sand fly infestation rate (sites with vector presence) was 11.1% and 83.33% in the first period, and 0% and 50.0% in the second period. No sand flies with Leishmania were identified via PCR. Lu. longipalpis presented an aggregate disposition with excellent adjustment. Rainfall and relative humidity were the abiotic factors that influenced the vector infestation level. The aggregate distribution for this species was predicted by the environmental factors that favor the proliferation of Lu. longipalpis. The results of this study should assist in devising measures to control sand flies in Dourados, Brazil.
The rationale of autologous hematopoietic stem cell transplantation (AHSCT) for autoimmune diseases is that high-dose immunosuppression eradicates autoreactive T and B cells, and the infused autologous hematopoietic stem cells promote reconstitution of a naive and self-tolerant immune system. The aim of this study was to evaluate the reconstitution of different B cell subsets, both quantitatively and functionally, in systemic sclerosis (SSc) patients treated with AHSCT.
Peripheral blood was harvested from twenty-two SSc patients before transplantation and at 30, 60, 120, 180 and 360 days post-AHSCT. Immunophenotyping of B cell subsets, B cell cytokine production, signaling pathways, and suppressive capacity of regulatory B cells (Bregs) were assessed by flow cytometry.
Naïve B cell frequencies increased from 60 to 360 days post-AHSCT, compared to pre-transplantation. Conversely, memory B cell frequencies decreased during the same period. Plasma cell frequencies transiently decreased at 60 days post-AHSCT. IL-10-producing Bregs CD19+CD24hiCD38hi and CD19+CD24hiCD27+ frequencies increased at 180 days. Moreover, the phosphorylation of ERK1/2 and p38MAPK proteins increased in B cells reconstituted post-AHSCT. Sivelestat cell line Notably, CD19+CD24hiCD38hi Bregs recovered their ability to suppress production of Th1 cytokines by CD4+ T cells at 360 days post-AHSCT. Finally, IL-6 and TGF-β1-producing B cells decreased following AHSCT.
Taken together, these results suggest improvements in immunoregulatory and anti-fibrotic mechanisms after AHSCT for SSc, which may contribute to reestablishment of self-tolerance and clinical remission.
Taken together, these results suggest improvements in immunoregulatory and anti-fibrotic mechanisms after AHSCT for SSc, which may contribute to reestablishment of self-tolerance and clinical remission.Sperm-oocyte binding initiates an outside-in signaling event in the mouse oocyte that triggers recruitment and activation of the cytosolic protein kinase PTK2B in the cortex underlying the bound sperm. While not involved in gamete fusion, PTK2B activity promotes actin remodeling events important during sperm incorporation. However, the mechanism by which sperm-oocyte binding activates PTK2B is unknown, and the present study examined the possibility that sperm interaction with specific oocyte surface proteins plays an important role in PTK2B activation. Imaging studies revealed that as IZUMO1R and CD9 became concentrated at the sperm binding site, activated (phosphorylated) PTK2B accumulated in the cortex underlying the sperm head and in microvilli partially encircling the sperm head. In order to determine whether IZUMO1R and/or CD9 played a significant role in PTK2B recruitment and activation at the sperm binding site, the ability of oocytes null for Izumo1r or Cd9, to initiate an increase in PTK2B content and activation was tested. The results revealed that IZUMO1R played a minor role in PTK2B activation and had no effect on actin remodeling; however, CD9 played a very significant role in PTK2B activation and subsequent actin remodeling at the sperm binding site. These findings suggest the possibility that interaction of sperm surface proteins with CD9 or CD9-associated oocyte proteins triggers PTK2B activation at the sperm binding site.
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