While a low level of ROS plays a role in cellular regulatory processes, a high level can lead to oxidative stress and cellular dysfunction. Insulin resistance (IR) is one of the dysfunctions in which oxidative stress occurs and, until now, the factors underlying the correlation between oxidative stress and IR were unclear and incomplete. This study aims to explore this correlation in skeletal muscle, a tissue relevant to insulin-mediated glucose disposal, using the hyperthyroid rat as a model of oxidative stress. The development of IR in the liver from hyperthyroid animals has been widely reported, whereas data concerning the muscle are quite controversial. Thus, we investigated whether hyperthyroidism induces IR in skeletal muscle and the role of oxidative stress in this process. Particularly, we compared the effects of hyperthyroidism on IR both in the absence and presence of vitamin E (Vit E), acting as an antioxidant. Putative correlations between ROS production, oxidative stress markers, antioxidant capacity and changes in intracellular signalling pathways related to insulin action (AKT) and cellular stress response (EIF2α; JNK; PGC1α; BIP; and NRF1) were investigated. Moreover, we assessed the effects of hyperthyroidism and Vit E on the expression levels of genes encoding for glucose transporters (Slc2a1; Slc2a4), factors involved in lipid homeostasis and insulin signalling (Pparg; Ppara, Cd36), as well as for one of the IR-related inflammatory factors, i.e., interleukin 1b (Il1b). Our results suggest that hyperthyroidism-linked oxidative stress plays a role in IR development in muscle and that an adequate antioxidant status, obtained by vitamin E supplementation, that mitigates oxidative stress, may prevent IR development.
We statistically validated a sample of hot Neptune candidates applying a two-step vetting technique using DAVE and TRICERATOPS. We performed a systematic validation of 250 transit-like events in the Transiting Exoplanet Survey Satellite (TESS) archive in the parameter region defined by P ≤ 4 d and 3 R⊕ ≤ R ≤ 5 R⊕. Through our analysis, we identified 18 hot Neptune-sized candidates, with a false positive probability $< 50\%$. Nine of these planet candidates still need to be confirmed. For each of the nine targets we retrieved the stellar parameters using ARIADNE and derived constraints on the planetary parameters by fitting the lightcurves with the juliet package. Within this sample of nine candidates, we statistically validated (i.e, with false positive probability $< 0.3\%$) two systems (TOI-277 b and TOI-1288 b) by re-processing the candidates with TRICERATOPS along with follow-up observations. These new validated exoplanets expand the known hot Neptunes population and are high-priority targets for future radial velocities follow-up.
Our understanding of the diversity of life on our planet and the possibility of finding or sustaining life elsewhere in the universe plays a central role in supporting human space settlement and exploration. Astrobiology and its outcomes require a multidisciplinary and comprehensive approach, in which the microbial, geological, chemical, astronomical, and physical domains of research are interlinked. An example of the applications of astrobiology and space microbiology is the use of extremophiles for in situ resource utilization through biomining and bioleaching. To better understand the multidisciplinary research landscape in this area, we quantitatively reviewed the global scientific literature on astrobiology, with a focus on biomining and bioleaching through bibliometric network analysis, investigating patterns and trends in its development over time. The network analysis of keyword co-occurrence highlights different connecting and overlapping clusters, illustrating the multidisciplinary character of astrobiology. Temporal analyses show a recent focus on topics related to microbiology and geomicrobiology, emphasizing the role that these fields will play in future astrobiology research. In conclusion, astrobiology, biomining, and bioleaching research are currently addressing the recognition of these techniques as valuable tools for biotechnological applications, expected to play a crucial role in long-term human space exploration.
High-density lipoprotein (HDL) is an anti-atherosclerotic lipoprotein. Thanks to the activity of apolipoprotein ApoA1, the principal protein component of HDL, this last is responsible for converting cholesterol into ester form and transporting excessive cholesterol to the liver (“reverse cholesterol transport” RCT). When HDL undergoes oxidation, it becomes dysfunctional and proatherogenic. ApoA1 is a target of oxidation, and its alteration affects RCT and contributes to atherosclerosis development. Until now, the mechanism of HDL oxidation is not fully understood and only hydroxyl radicals seem to induce direct oxidation of protein and lipidic components of lipoproteins. Here we demonstrate that superoxide radical, widely produced in early atherosclerosis, directly oxidizes HDL, and as a consequence, ApoA1 undergoes structural alterations impairing its anti-atherosclerotic functions. Our results highlight in an in vitro system the potential mechanism by which O2·− triggers atherosclerotic pathogenesis in vivo. Our study gets the basis for therapeutic approaches focused on the management of superoxide generation in early atherosclerosis onset.
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