Stem cell paracrine actions in tissue regeneration and potential therapeutic effect in human endometrium: a retrospective study.

OBJECTIVE: Determining genetic and paracrine mechanisms behind endometrial regeneration in Asherman's syndrome and endometrial atrophy (AS/EA) patients after autologous CD133+ bone marrow-derived stem cell (CD133+ BMDSC) transplantation. DESIGN: Retrospective study using human endometrial biopsies and mouse models. SETTING: Fundación-IVI, IIS-La Fe, Valencia, Spain. SAMPLES: Endometrial biopsies collected before and after CD133+ BMDSC therapy, from eight women with AS/EA (NCT02144987) from the uterus of five mice with only left horns receiving CD133+ BMDSC therapy. METHODS: In human samples, haematoxylin and eosin (H&E) staining, RNA arrays, PCR validation, and neutrophil elastase (NE) immunohistochemistry (IHQ). In mouse samples, PCR validation and protein immunoarrays. MAIN OUTCOME MEASURES: H&E microscopic evaluation, RNA expression levels, PCR, and growth/angiogenic factors quantification, NE IHQ signal. RESULTS: Treatment improved endometrial morphology and thickness for all patients. In human samples, Jun, Serpine1, and Il4 were up-regulated whereas Ccnd1 and Cxcl8 were down-regulated after treatment. The significant decrease of NE signal corroborated Cxcl8 expression. Animal model analysis confirmed human results and revealed a higher expression of pro-angiogenic cytokines (IL18, HGF, MCP-1, MIP2) in treated uterine horns. CONCLUSIONS: CD133+ BMDSC seems to activate several factors through a paracrine mechanism to help tissue regeneration, modifying endometrial behaviour through an immunomodulatory milieu that precedes proliferation and angiogenic processes. Insight into these processes could bring us one step closer to a non-invasive treatment for AS/EA patients. TWEETABLE ABSTRACT: CD133+ BMDSC therapy regenerates endometrium, modifying the immunological milieu that precedes proliferation and angiogenesis.

Leg fat might be more protective than arm fat in relation to lipid profile.

PURPOSE: The objective of this study was to determine the independent relationships of trunk fat, leg fat and arm fat to cardiovascular (CVD) risk factors, after controlling for relevant confounders such as fat mass index, cardiorespiratory fitness and objectively measured physical activity. METHODS: This is a cross-sectional study involving 683 university students, aged 18-30 years. Total and regional body fat distribution was measured using dual-energy X-ray absorptiometry. The associations of trunk, leg and arm fat with CVD risk factors (triglycerides-TG-, high-density lipoprotein cholesterol-HDL-c-, TG/HDL-c ratio, HOMA(IR), mean arterial pressure, C-reactive protein) were examined using regression linear models, controlling for age, sex, fat mass index [total body fat(kg)/height(m(2))], maximal oxygen consumption and physical activity by accelerometer. RESULTS: After controlling for fat mass index, and other confounders, higher levels of trunk fat were found to be associated with a poorer lipid profile, while higher levels of leg fat were found to be associated with a better lipid profile. We did not find any association between arm fat and lipid profile after controlling for total fatness and other confounders. Neither trunk, leg or arm fat was found to be related to insulin resistance, blood pressure or inflammation markers. CONCLUSIONS: Our data suggest that the region where fat is accumulated might have a differential effect on lipid profile: trunk fat has an adverse effect, leg fat has a protective effect, and arm fat has no effect. The differences observed between upper- and lower-body peripheral fat depots should be further explored.

Contaminated soil phytoremediation by Cyperus laxus Lam. cytochrome p450 EROD-activity induced by hydrocarbons in roots.

Laboratory and greenhouse experiments with Cyperus laxus Lam were conducted to determine the rate and extent of phytoremediation and the effect of hydrocarbons on the cytochrome P450 EROD (7-ethoxyresorufin-O-deethylase) enzymatic activity in roots. Plants were cultivated on hydrocarbon-contaminated soil (HCS) and spiked perlite. Phytoremediation was evaluated using 6.5 kg HCS (173 +/- 15 mg total petroleum hydrocarbons [TPH] g(-1) of dry soil) pots at different moisture contents; the average removal rate was 3.46-0.25 mg TPH g(-1) dry soil month(-1) and 48% was removed when moisture was kept at 60%. The aromatic hydrocarbon fraction was the mostly removed, 60%; aliphatic, 51%; and polar 24% after 24-month experiments. In unplanted pots, TPH concentration did not exhibit significant differences with respect to the initial concentration. We confirmed that the presence of hydrocarbons induced ERODactivity up to 6.5-fold. Moreover, short-term experiments (up to 13 d) with spiked perlite demonstrated that two EROD activities in roots contributed to the total detected; 60% was found in the cytosolic and 40% in the microsomal fraction. To our knowledge, this is the first work that tries to build links between the hydrocarbon-inducible character of ERODactivity in roots and the phytoremediation ability of C. laxus in highly contaminated soils.