Hypertension is a major public health problem among the aging population worldwide. It causes cardiac remodeling, including hypertrophy and interstitial fibrosis, which leads to development of hypertensive heart disease (HHD). Although microRNA-21 (miR-21) is associated with fibrogenesis in multiple organs, its contribution to cardiac remodeling in hypertension is poorly understood. Circulating miR-21 level was higher in patients with HHD than that in the control subjects. SBI-0206965 It also positively correlated with serum myocardial fibrotic markers. MiR-21 expression levels were significantly upregulated in the mice hearts after angiotensin II (Ang II) infusion or transverse aortic constriction (TAC) compared with control mice. Expression level of programmed cell death 4 (PDCD4), a main target of miR-21, was significantly decreased in Ang II infused mice and TAC mice compared with control mice. Expression levels of transcriptional activator protein 1 (AP-1) and transforming growth factor-β1 (TGF-β1), which were downstream targets of PDCD4, were increased in Ang II infused mice and TAC mice compared with control mice. In vitro, mirVana-miR-21-specific inhibitor attenuated Ang II-induced PDCD4 downregulation and contributed to subsequent deactivation of AP-1/TGF-β1 signaling pathway in neonatal rat cardiomyocytes. Thus, suppression of miR-21 prevents hypertrophic stimulation-induced cardiac remodeling by regulating PDCD4, AP-1, and TGF-β1 signaling pathway.In this work we present a framework for blood cholesterol levels prediction from genotype data. The predictor is based on an algorithm for cholesterol metabolism simulation available in literature, implemented and optimized by our group in the R language. The main weakness of the former simulation algorithm was the need of experimental data to simulate mutations in genes altering the cholesterol metabolism. This caveat strongly limited the application of the model in the clinical practice. In this work we present how this limitation could be bypassed thanks to an optimization of model parameters based on patient cholesterol levels retrieved from literature. Prediction performance has been assessed taking into consideration several scoring indices currently used for performance evaluation of machine learning methods. Our assessment shows how the optimization phase improved model performance, compared to the original version available in literature.Consequences of heat stress during pregnancy can affect the normal development of the offspring. In the present experiment, 30 Murciano-Granadina dairy goats (41.8 ± 5.7 kg) were exposed to 2 thermal environments varying in temperature-humidity index (THI) from 12 days before mating to 45 days of gestation. The environmental conditions were gestation under thermal-neutral (TN; THI = 71 ± 3); and gestation under heat stress (HS; THI = 85 ± 3) conditions. At 27 ± 4 days old, female kids exposed to in utero TN (IUTN; n = 16) or in utero HS (IUHS; n = 10) were subjected to 2 tests arena test (AT) and novel object test (NOT), the latter was repeated at 3 months of age. Additionally, 8 months after birth, a subset of IUTH and IUHS growing goats (n = 8 each; 16.8 ± 3.4 kg BW) were exposed to 2 environmental conditions in 2 consecutive periods a basal thermal-neutral period (THI = 72 ± 3) for 7 days, and a heat-stress period (THI = 87 ± 2) for 21 days. In both periods, feeding, resting, posture, and thermally-associated behaviors were recorded. The gestation length was shortened by 3 days in GHS goats. In the AT, IUHS kids showed a lower number of sniffs (P less then 0.01) compared to IUTN. In the NOT, IUHS kids also tended to show a lower number of sniffs (P = 0.09). During heat exposure, IUTN and IUHS growing goats spent more time resting and exhibited more heat-stress related behaviors such as panting and drinking (P less then 0.001); however, no differences were observed between both groups. In conclusion, heat stress during the first third of pregnancy shortened gestation length and influenced the exploratory behavior of the kids in the early life. However, behavior responses to heat stress during the adulthood were not affected by the in utero thermal treatment.Adipose tissue derived mesenchymal stem/stromal cell (ASC)-derived extracellular vesicles (EV) have been reported to be beneficial against dextran sulfate sodium (DSS)-induced colitis in mice. However, the underlying mechanisms have not been fully elucidated. We hypothesize that the tumor necrosis factor-α-stimulated gene/protein 6 (TSG-6) in EVs is a key factor influencing the alleviation of colitis symptoms. DSS-induced colitis mice (C57BL/6, male, Naïve = 6, Sham = 8, PBS = 8 EV = 8, CTL-EV = 8, TSG-6 depleted EV = 8) were intraperitoneally administered EVs (100 ug/mice) on day 1, 3, and 5; colon tissues were collected on day 10 for histopathological, RT-qPCR, western blot and immunofluorescence analyses. In mice injected with EV, inflammation was alleviated. Indeed, EVs regulated the levels of pro- and anti-inflammatory cytokines, such as TNF-α, IL-1β, IFN-γ, IL-6, and IL-10 in inflamed colons. However, when injected with TSG-6 depleted EV, the degree of inflammatory relief was reduced. Furthermore, TSG-6 in EVs plays a key role in increasing regulatory T cells (Tregs) and polarizing macrophage from M1 to M2 in the colon. In conclusion, this study shows that TSG-6 in EVs is a major factor in the relief of DSS-induced colitis, by increasing the number of Tregs and macrophage polarization from M1 to M2 in the colon.The North American cheetah population serves as a reservoir for the species, and acts as a research population to help understand the unique biology of the species. Little is known about the intrauterine physiology of the cheetah, including embryo differentiation, implantation, and the development of the placenta. After mating, cheetah females frequently experience (30-65% of matings) a non-pregnant luteal phase where progestogen metabolite levels match those found in pregnant females for the first ~55 days of gestation, but parturition does not occur. Immunoglobulin J chain (IgJ) is a molecule that is involved in the activation of the secretory immune response and has been found to be indicative of pregnancy in the cheetah using fecal monitoring. In this study, western blotting was employed to track IgJ abundance in pooled weekly fecal samples following natural breeding or exogenous stimulation to ovulate, and IgJ levels were compared between individuals undergoing a pregnant (n = 12) and non-pregnant (n = 19) luteal phase.