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These events were independent of expression levels of XIAP. Taken together, our results suggest that BAX oligomerization comprises a critical step by which 6-OHDA-induced dysregulated autophagy mediates neuronal apoptosis.Autophagy is an intracellular pathway that degrades unnecessary proteins and organelles and provides energy substrates during cellular ischemic conditions. Although pharmacological myocardial preconditioning with an autophagy inducer has been reported to protect cells against ischemic reperfusion (I/R), the effects of preconditioning using naturally occurring substances are still unknown. We aimed to examine whether autophagic preconditioning with trehalose improves cardiac function after myocardial stunning by global ischemia in rats. Rat hearts were perfused by oxygenized Krebs Henseleit (KH) solution in Langendorff system. Ten rats were randomized into the following two groups according to the perfusates during the preconditioning control (KH solution only, n = 5) and trehalose (KH + 2% trehalose, n = 5). After the 35-min preconditioning period and subsequent 20 min of global ischemia, the hearts were reperfused for 60 min. Cardiac function was assessed during the reperfusion. To evaluate autophagy, myocardial protein expression of microtubule-associated protein light chain 3 (LC3) II was evaluated by western blotting. During I/R, a systolic functional parameter, maximum dP/dt was significantly higher; meanwhile, coronary flow tended to be higher in the trehalose group than in the control group. Myocardial LC3-II expression after preconditioning was higher in the trehalose group than in the control group and decreased to the control level after I/R. In conclusion, in a rat model of global myocardial ischemia, trehalose preconditioning improved cardiac function during I/R. Further studies would be needed to identify the mechanism and effects of trehalose preconditioning.Malodorous compounds induce stress responses, mood changes, an increase of skin conductance, activation of the sympathetic nervous system and other physiological changes, and it has been suggested that sensing malodors could provide warning of danger to health. Furthermore, the human body secretes various malodorous compounds as waste products of metabolism, including trans-2-nonenal ((E)-2-nonenal), the amount of which increases with aging. In the present study, we examined the effects of some endogenous malodorous compounds ((E)-2-nonenal, nonanal, pentanal, hexanal, hexanoic acid, hexylamine and isovaleric acid) on cultured human keratinocytes. (E)-2-Nonenal decreased the viability and promoted apoptosis of cultured keratinocytes. It also reduced the thickness and the number of proliferative cells in a three-dimensional epidermal equivalent model. Co-application of masking odorants (dihydromycenol, benzaldehyde, linalool, phenethyl alcohol, benzyl acetate and anisaldehyde), but not non-masking odorants (1,8-cineol, β-damascone, and o-t-butylcyclohexyl acetate), reduced the effect of (E)-2-nonenal on keratinocyte proliferation, and restored the thickness and number of proliferative cells in a three-dimensional epidermal equivalent model.Blood is generally modeled as a Newtonian fluid, assuming a standard and constant viscosity; however, this assumption may not hold for the highly pulsatile and recirculating intracavitary flow in the left ventricle (LV), hampering the quantification of fluid dynamic indices of potential clinical relevance. Herein, we investigated the effect of three viscosity models on the patient-specific quantification of LV blood energetics, namely on viscous energy loss (EL), from 4D Flow magnetic resonance imaging I) Newtonian with standard viscosity (3.7 cP), II) Newtonian with subject-specific hematocrit-dependent viscosity, III) non-Newtonian accounting for the effect of hematocrit and shear rate. Analyses were performed on 5 controls and 5 patients with cardiac light-chain amyloidosis. In Model II, viscosity ranged between 3.0 (-19%) and 4.3 cP (+16%), mildly deviating from the standard value. In the non-Newtonian model, this effect was emphasized viscosity ranged from 3.2 to 6.0 cP, deviating maximally from the standard value in low shear rate (i.e., less then 100 s-1) regions. This effect reflected on EL quantifications in particular, as compared to Model I, Model III yielded markedly higher EL values (up to +40%) or markedly lower (down to -21%) for subjects with hematocrit higher than 39.5% and lower than 30%, respectively. Accounting for non-Newtonian blood behavior on a patient-specific basis may enhance the accuracy of intracardiac energetics assessment by 4D Flow, which may be explored as non-invasive index to discriminate between healthy and pathologic LV.Spine musculoskeletal (MS) models make simplifying assumptions on the intervertebral joint degrees-of-freedom (rotational and/or translational), representation (spherical or beam-like joints), and properties (linear or nonlinear). They also generally neglect the realistic structure of the joints with disc nuclei/annuli, facets, and ligaments. We aim to develop a novel MS model where trunk muscles are incorporated into a detailed finite element (FE) model of the ligamentous T12-S1 spine thus constructing a gold standard coupled MS-FE model. Model predictions are compared under some tasks with those of our earlier spherical joints, beam joints, and hybrid (uncoupled) MS-FE models. The coupled model predicted L4-L5 intradiscal pressures (R2 ≅ 0.97, RMSE ≅ 0.27 MPa) and L1-S1 centers of rotation (CoRs) in agreement to in vivo data. https://www.selleckchem.com/products/Nolvadex.html Differences in model predictions grew at larger trunk flexion angles; at the peak (80°) flexion the coupled model predicted, compared to the hybrid model, much smaller global/local muscle forces (~38%), segmental (~44%) and disc (~22%) compression forces but larger segmental (~9%) and disc (~17%) shear loads, ligament forces at the lower lumbar levels (by up to 57%) and facet forces at all levels. The spherical/beam joints models predicted much greater muscle forces and segmental loads under larger flexion angles. Unlike the spherical joints model with fixed CoRs, the beam joints model predicted CoRs closer (RMSE = 2.3 mm in flexion tasks) to those of the coupled model. The coupled model offers a great potential for future studies towards improvement of surgical techniques, management of musculoskeletal injuries and subject-specific simulations.
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