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Many diseases are clinically related to oxidative stress. Obstructive sleep apnea (OSA) is a common disease with oxidative stressin clinical practice, which is mostly associated with cardio-cerebrovascular diseases. It has been shown that the level of oxidative stress increases and the level of antioxidant copper zinc superoxide dismutase (SOD1) decreases in intermittent hypoxia (IH). SOD1 is one of the key antioxidant enzymes in organisms, and it can also be used as a signal transmission controller. Its abnormal expression further affects organ functions, but the specific mechanism is not yet fully clear.
We downregulated the SOD1 gene in H9C2 cell line, using high-throughput RNA sequencing (RNA-seq) to find differentially expressed genes (DEGs) related to cardiomyocyte function by using GO and KEGG databases to annotate, enrich and analyze the metabolic pathways of DEGs.
Through the analysis of these functional gene changes, we can understand the regulation of SOD1 downregulation on cardiomyocyte funcnd CCL7 genes are all related to inflammation.
The gene and signaling pathways involved in oxidative stress and inflammatory response process regulated by SOD1 were demonstrated. SOD1 may affect the function of the heart by affecting myocardial contraction, inflammation, lipid metabolism, and other pathways. It is inferred that they may also play a role in the process of OSA-related myocardial injury, which is worthy of attention and further study.
The gene and signaling pathways involved in oxidative stress and inflammatory response process regulated by SOD1 were demonstrated. SOD1 may affect the function of the heart by affecting myocardial contraction, inflammation, lipid metabolism, and other pathways. It is inferred that they may also play a role in the process of OSA-related myocardial injury, which is worthy of attention and further study.The aim of the present study was to evaluate the efficiency of using in vitro fertilization to validate semen fertility for artificial insemination. Cryopreserved semen from ten bulls (five Nelore and five Brangus bulls) was evaluated using in vitro production of embryos (IVPE) and via fixed-time artificial insemination (FTAI). There was variation (p less then 0.05) in the IVPE (20.9 to 53.7% of blastocyst production) and in the FTAI (42.0 to 56.0% of pregnant cows) results among the semen evaluated. According to the results, there was a positive correlation (rs = 0.8378; p = 0.0001) between the rate of blastocyst production (using IVPE) and the rate of pregnancy (using FTAI) using Nelore bull semen. Variation (p less then 0.05) was also found using semen from Brangus bulls, in the rates of blastocyst production (36.5 to 47.0%) and pregnancy (45.6 to 52.2%) via FTAI. There was also a positive correlation (rs = 0.8786; p = 0.0001) between the rates of blastocyst production (IVPE) and pregnancy (FTAI) when using Brangus bull semen. According to the results, IVPE may be used in addition to conventional semen analysis to evaluate and validate the semen fertility of bulls for artificial insemination programs.Trophically transmitted parasites have life cycles that require the infected host to be eaten by the correct type of predator. Such parasites should benefit from an ability to suppress the host's fear of predators, but if the manipulation is imprecise the consequence may be increased predation by non-hosts, to the detriment of the parasite. Three-spined sticklebacks (Gasterosteus aculeatus) infected by the cestode Schistocephalus solidus express reduced antipredator behaviours, but it is unknown whether this is an example of a highly precise manipulation, a more general manipulation, or if it can even be attributed to mere side effects of disease. In a series of experiments, we investigated several behaviours of infected and uninfected sticklebacks. As expected, they had weak responses to simulated predatory attacks compared to uninfected fish. However, our results suggest that the parasite induced a general fearlessness, rather than a precise manipulation aimed at the correct predators (birds). Infected fish had reduced responses also when attacked from the side and when exposed to odour from a fish predator, which is a "dead-end" for this parasite. We also tested whether the reduced anti-predator behaviours were mere symptoms of a decreased overall vigour, or due to parasite-induced hunger, but we found no support for these ideas. We propose that even imprecise manipulations of anti-predator behaviours may benefit parasites, for example, if other behaviours are altered in a way that increases the exposure to the correct predator.Mutant KRAS is a key driver in colorectal cancer (CRC) and promotes Myc translation and Myc-dependent stress adaptation and proliferation. Here, we report that the combination of two FDA-approved drugs Bortezomib and Everolimus (RAD001) (BR) is highly efficacious against mutant KRAS CRC cells. Mechanistically, the combination, not single agent, rapidly depletes Myc protein, not mRNA, and leads to GCN2- and p-eIF2α-dependent cell death through the activation of extrinsic and intrinsic apoptotic pathways. Cell death is selectively induced in mutant KRAS CRC cells with elevated basal Myc and p-eIF2α and is characterized by CHOP induction and transcriptional signatures in proteotoxicity, oxidative stress, metabolic inhibition, and immune activation. BR-induced p-GCN2/p-eIF2α elevation and cell death are strongly attenuated by MYC knockdown and enhanced by MYC overexpression. The BR combination is efficacious against mutant KRAS patient derived organoids (PDO) and xenografts (PDX) by inducing p-eIF2α/CHOP and cell death. Interestingly, an elevated four-gene (DDIT3, GADD45B, CRYBA4 and HSPA1L) stress signature is linked to shortened overall survival in CRC patients. These data support that Myc-dependent stress adaptation drives the progression of mutant KRAS CRC and serves as a therapeutic vulnerability, which can be targeted using dual translational inhibitors.
Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) represents a minimally invasive technique of aortic occlusion (AO). It has been demonstrated to be safe and effective with appropriate training in traumatic hemorrhage with hemodynamic instability; however, its indications are still debated. The aim of this systematic review and meta-analysis is to assess the impact of REBOA on mortality in torso trauma patient with severe non-compressible hemorrhage compared to other temporizing hemostatic techniques.
The primary outcome is represented by 24-h, and in-hospital mortality. Secondary outcomes are post-procedural hemodynamic improvement (systolic blood pressure-SBP), mean injury severity score (ISS) differences, treatment-related morbidity, transfusional requirements and identification of prognostic factors.
A significant survival benefit at 24h (RR 0.46; 95% CI 0.27-0.79; I
55%; p = 0.005) was highlighted in patients undergoing REBOA. Regarding in-hospital mortality (RR 0.99; 95% CI 0.75-1.32; I
73%; p = 0.98) no differences in risk of death were noticed. A hemodynamic improvement-although not significant-was highlighted, with 55.8mmHg post-AO SBP mean difference between REBOA and control groups. A significantly lower mean number of packed Red Blood Cells (pRBCs) was noticed for REBOA patients (mean difference - 3.02; 95% CI - 5.79 to - 0.25; p = 0.033). Nevertheless, an increased risk of post-procedural complications (RR 1.66; 95% CI 0.39-7.14; p = 0.496) was noticed in the REBOA group.
REBOA may represent a valid tool in the initial treatment of multiple sites subdiaphragmatic hemorrhage with refractory hemodynamic instability. However, due to several important limitations of the present study, our findings should be interpreted with caution.
Level III according to ELIS (SR/MA with up to two negative criteria).
Level III according to ELIS (SR/MA with up to two negative criteria).Data generated over nearly two decades clearly demonstrate the importance of epigenetic modifications and mechanisms in the pathogenesis of type 2 diabetes. However, the role of pharmacoepigenetics in type 2 diabetes is less well established. The field of pharmacoepigenetics covers epigenetic biomarkers that predict response to therapy, therapy-induced epigenetic alterations as well as epigenetic therapies including inhibitors of epigenetic enzymes. Not all individuals with type 2 diabetes respond to glucose-lowering therapies in the same way, and there is therefore a need for clinically useful biomarkers that discriminate responders from non-responders. Blood-based epigenetic biomarkers may be useful for this purpose. There is also a need for a better understanding of whether existing glucose-lowering therapies exert their function partly through therapy-induced epigenetic alterations. Finally, epigenetic enzymes may be drug targets for type 2 diabetes. Here, I discuss whether pharmacoepigenetics is clinically relevant for type 2 diabetes based on studies addressing this topic.
High-fat and low-fibre discretionary food intake and FTO genotype are each associated independently with higher risk of obesity. However, few studies have investigated links between obesity and dietary patterns based on discretionary food intake, and the interaction effect of FTO genotype are unknown. Thus, this study aimed to derive dietary patterns based on intake of discretionary foods, saturated fatty acids (SFA) and fibre, and examine cross-sectional associations with BMI and waist circumference (WC), and interaction effects of FTO genotype.
Baseline data on 1280 adults from seven European countries were included (the Food4Me study). Dietary intake was estimated from a Food Frequency Questionnaire. Reduced rank regression was used to derive three dietary patterns using response variables of discretionary foods, SFA and fibre density. DNA was extracted from buccal swabs. Anthropometrics were self-measured. Linear regression analyses were used to examine associations between dietary patterns and BMI and WC, with an interaction for FTO genotype.
Dietary pattern 1 (positively correlated with discretionary foods and SFA, and inversely correlated with fibre) was associated with higher BMI (β0.64; 95% CI 0.44, 0.84) and WC (β1.58; 95% CI 1.08, 2.07). There was limited evidence dietary pattern 2 (positively correlated with discretionary foods and SFA) and dietary pattern 3 (positively correlated with SFA and fibre) were associated with anthropometrics. FTO risk genotype was associated with higher BMI and WC, with no evidence of a dietary interaction.
Consuming a dietary pattern low in discretionary foods and high-SFA and low-fibre foods is likely to be important for maintaining a healthy weight, regardless of FTO predisposition to obesity.
Clinicaltrials.gov NCT01530139. Registered 9 February 2012 https//clinicaltrials.gov/ct2/show/NCT01530139.
Clinicaltrials.gov NCT01530139. Registered 9 February 2012 https//clinicaltrials.gov/ct2/show/NCT01530139.
Higher total fruit and vegetable (FV) intakes have been associated with lower perceived stress. The relationship between specific types of FV and perceived stress remains uncertain. The aims of this cross-sectional study were to explore the relationship between consumption of specific types of FV with perceived stress in a population-based cohort of men and women aged ≥ 25years from the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study.
Dietary intake was assessed using a validated Food Frequency Questionnaire (n = 8,640). Perceived stress was evaluated using a validated Perceived Stress Questionnaire, with values ranging 0-1 (lowest to highest). High perceived stress cut-offs of ≥0.34 for men and ≥0.39 for women were obtained from the highest quartile of the perceived stress score for each sex. Multivariable-adjusted logistic regression was performed to investigate the associations.
The mean age of participants (50.1% females) was 47.8 (SD 15) years. Persons in the highest, versus lowest, quartiles of apples and pears, orange and other citrus, and banana intakes had a significantly lower odds (24-31%) of having high perceived stress.
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