Purcellgrace0590

Obstructive sleep apnea (OSA) patients are at risk for increased blood pressure and carotid intima-media thickness (IMT), with pulmonary hypertension and right-sided heart failure potentially developing as well. Chronic intermittent hypoxia (IH) has been used as an OSA model in animals, but its effects on vascular beds have not been evaluated using objective unbiased tools. Previously published and current experimental data in mice exposed to IH were evaluated for IMT in aorta and pulmonary artery (PA) after IH with or without normoxic recovery using software for meta-analysis, Review Manager 5. Because IMT data reports on PA were extremely scarce, atherosclerotic area percentage from lumen data was also evaluated. IH significantly increased IMT parameters in both aorta and PA as illustrated by Forest plots (P less then 0.01), which also confirmed that IMT values after normoxic recovery were within the normal range in both vascular beds. One-sided scarce lower areas in Funnel Plots were seen for both aorta and PA indicating the likelihood of significant publication bias. Forest and Funnel plots, which provide unbiased assessments of published and current data, suggest that IH exposures may induce IMT thickening that may be reversed by normoxic recovery in both aorta and PA. In light of the potential likelihood of publication bias, future studies are needed to confirm or refute the findings. In conclusion, OSA may induce IMT thickening (e.g., aorta and/or PA), but the treatment (e.g., nasal continuous positive airway pressure) will likely lead to improvements in such findings.Overwhelming evidence has shown the significant role of the tumor microenvironment (TME) in governing the triple-negative breast cancer (TNBC) progression. Digital pathology can provide key information about the spatial heterogeneity within the TME using image analysis and spatial statistics. These analyses have been applied to CD8+ T cells, but quantitative analyses of other important markers and their correlations are limited. In this study, a digital pathology computational workflow is formulated for characterizing the spatial distributions of five immune markers (CD3, CD4, CD8, CD20, and FoxP3) and then the functionality is tested on whole slide images from patients with TNBC. The workflow is initiated by digital image processing to extract and colocalize immune marker-labeled cells and then convert this information to point patterns. Afterward invasive front (IF), central tumor (CT), and normal tissue (N) are characterized. For each region, we examine the intra-tumoral heterogeneity. The workflow is then repeated for all specimens to capture inter-tumoral heterogeneity. In this study, both intra- and inter-tumoral heterogeneities are observed for all five markers across all specimens. Among all regions, IF tends to have higher densities of immune cells and overall larger variations in spatial model fitting parameters and higher density in cell clusters and hotspots compared to CT and N. learn more Results suggest a distinct role of IF in the tumor immuno-architecture. Though the sample size is limited in the study, the computational workflow could be readily reproduced and scaled due to its automatic nature. Importantly, the value of the workflow also lies in its potential to be linked to treatment outcomes and identification of predictive biomarkers for responders/non-responders, and its application to parameterization and validation of computational immuno-oncology models.Aspirin eugenol ester (AEE) is a new potential drug with anti-inflammatory and antioxidant stress pharmacological activity. Paraquat (PQ) is an effective and commercially important herbicide that is widely used worldwide. However, paraquat is highly toxic and can cause various complications and acute organ damage, such as liver, kidney and lung damage. The purpose of this study was to investigate whether AEE has a protective effect on hepatotoxicity induced by PQ in vivo and in vitro. Cell viability, apoptosis rate, mitochondrial function and intracellular oxidative stress were detected to evaluate the protective effect of AEE on PQ-induced BRL-3A (normal rat hepatocytes) cytotoxicity in vitro. In vivo, AEE pretreatment could attenuate oxidative stress and histopathological changes in rat liver induced by PQ. The results showed that AEE could reduce the hepatotoxicity induced by PQ in vivo and in vitro. AEE reduced PQ-induced hepatotoxicity by inhibitingoxidative stress and maintaining mitochondrial function. This study proved that AEE is an effective antioxidant and can reduce the hepatotoxicity of PQ.

Ameloblasts are epithelially derived cells responsible for enamel formation through a process known as amelogenesis. Amongst the several transcription factors that are expressed during amelogenesis, both

and

transcription factors play important role.

and

mouse mutants, exhibit similar amelogenesis defects, namely enamel hypoplasia, while humans with amelogenesis imperfecta (AI) carry mutations in the human homologues of MSX2 or SP6 genes. These across species similarities in function indicate that these two transcription factors may reside in the same developmental pathway. In this paper, we test whether they work in a coordinated manner to exert their effect during amelogenesis.

Two different dental epithelial cell lines, the mouse LS8 and the rat G5 were used for either overexpression or silencing of

or

or both.

mutant mouse embryos or pups were used for

studies.

hybridization, semi-quantitative and quantitative real time PCR were employed to study gene expression pattern.

lts show that

and

work in a concerted manner to form part of a network of transcription factors that operate during later stages of tooth development controlling ameloblast life cycle and amelogenesis.

Collectively, these results show that Sp6 and Msx2 work in a concerted manner to form part of a network of transcription factors that operate during later stages of tooth development controlling ameloblast life cycle and amelogenesis.Exercise-induced oxidative stress is linked with the expression level of endogenous antioxidants, but these antioxidants cannot overcome all oxidative stress-related damages in the cells, particularly when cells are under physiological stress. Sometimes, compounds are needed for cellular function, which are produced/activated within the cells, and these compounds can be synthesized by performing exercise, especially high-performance exercise. Taurine is a sulfur-containing amino acid used for various physiological functions. However, its synthesis and accumulation under the oxidative environment may be compromised. Recently, we have shown that taurine level is increased during exercise performance with a decrease in oxidative damage in overused muscles. Other studies have also shown that short-term supplementation with taurine increased physiological performance during severe work intensities, suggesting the role of taurine in improving muscle performance during exercise. However, its precursor cysteine is used in the synthesis of other compounds like GSH and Coenzyme A, which are important for regulating the redox system and energy homeostasis. It is, therefore, important to understand whether taurine synthesis within the cells can blunt the activity of other compounds that are beneficial in preventing oxidative damage during intense exercise. Furthermore, it is important to understand whether taurine supplementation can prevent the conditions observed in the physiological stress of muscles. This review discusses how taurine synthesis could alter exercise-induced ROS generation and the relationship between the physiological stress of muscle and subsequent improvements in exercise performance.

Regnase-1 (MCPIP) has been identified as an anti-inflammatory agent, but little is known about its influence on liver ischemia/reperfusion (I/R) injury. Macrophages can evolve biphasic responses and differentiate into remarkable polarizations, contributing greatly to the uncontrolled inflammatory cascades during liver I/R injury. Therefore, the aim of this study was to explore whether regnase-1 participated in liver I/R via manipulating macrophage polarization.

C57BL/6 mice were randomly divided into five groups Sham, I/R, Clodronate, Clo + BMDM, and Clo + LV MCPIP BMDM. A liver I/R model was established, and histopathological and immunostaining examinations were performed for the liver specimens; double immunofluorescence staining was used to localize MCPIP in the liver. Primary hepatocytes were isolated to simulate a hypoxia and reoxygenation (H/R) model

. Bone marrow-derived macrophages (BMDM) were extracted and subjected to lentiviral transduction to knockdown MCPIP expression. BMDM with or without LV-MCPIP BMDM posed a higher ratio of M1/M2 than BMDM. Finally, we found that MCPIP participated in macrophage M1/M2 polarization through the NF-κB, C/EBPβ, and PPARγ signaling pathways during liver I/R.

Our study confirms that regnase-1 plays a critical role in liver I/R via regulation of macrophage polarization and, thus, might offer a potential therapeutic target.

Our study confirms that regnase-1 plays a critical role in liver I/R via regulation of macrophage polarization and, thus, might offer a potential therapeutic target.The aim was to investigate the effect of training, sex, age and selected genes on physiological and performance variables and adaptations before, and during 6 months of training in well-trained cross-country skiers. National-level cross-country skiers were recruited for a 6 months observational study (pre - post 1 - post 2 test). All participants were tested in an outside double poling time trial (TTDP), maximal oxygen uptake in running (RUN-VO2max), peak oxygen uptake in double poling (DP-VO2peak), lactate threshold (LT) and oxygen cost of double poling (CDP), jump height and maximal strength (1RM) in half squat and pull-down. Blood samples were drawn to genetically screen the participants for the ACTN3 R577X, ACE I/D, PPARGC1A rs8192678, PPARG rs1801282, PPARA rs4253778, ACSL1 rs6552828, and IL6 rs1474347 polymorphisms. The skiers were instructed to train according to their own training programs and report all training in training diaries based on heart rate measures from May to October. 29 skiers completeding for the whole group. No differences were observed in training progression or training adaptation between sexes or age-groups. In conclusion, sex and age affected physiological and performance variables, with only a minor impact from selected genes, at baseline. However, minor to no effect of sex, age, selected genes or the participants training were shown on training adaptations. Increased total training volume did not affect physiological and performance variables.This study aimed to propose a conditioning activity (CA) model to stimulate improvement on neuromuscular responses, mechanical parameters and for the 50-m freestyle swimming. Thirteen male swimmers (19 ± 3 years and performances of 77% in relation to World Championship records) performed four CA protocols followed by a maximum performance in the 50-m freestyle. In the first protocol (P1) swimmers performed a standard warm-up (∼15 min); in the second protocol (P2) lunges (3 × 85% of the one-repetition maximum); in the third (P3) pull-ups (3 maximum repetitions) and box jumps 40 cm high and 60 cm deep (1 × 5 with 10% of the corporal weight); and in the fourth protocol (P4) a combination of exercises from the second and third protocols. CA protocols had no effect on the standard warm-up. However, P2 performance (27.01 ± 1.25 s) was similar to P1 (27.01 ± 1.18 s) and presented higher positive effects in mechanical parameters for the swim start performance in comparison to other protocols, contributing to improvements in the 50-m freestyle.