Chaperoning histones with the Genetics repair party

Overall, our findings suggest that SLP-2 controls the JAK2-STAT3-PIM1 oncogenic pathway, offering a rationale for a novel therapeutic strategy with combined SGI-1776 and TG-101348 in CRC. Additionally, SLP-2 may be a prognostic marker and biomarker for sensitivity to JAK2 and PIM1 inhibitors. © 2020 The Authors.A plethora of previous studies have been focused on the role of indoleamine 2,3-dioxygenase 1 (IDO1) in cancer immunity; however, the alternative way of targeting tryptophan 2,3-dioxygenase (TDO2) in cancer immunotherapy has been largely ignored. In particular, the specific role of TDO2 in breast cancer remains unclear. In the present study, we systematically explored and validated the expression and prognostic value of TDO2 in breast cancer using large-scale transcriptome data. We observed overexpression of TDO2 in many types of cancer tissues compared with adjacent normal tissues. TDO2 overexpression was revealed to be positively correlated with malignancy and tumor grade in breast cancer. TDO2 expression was higher in estrogen-negative breast cancer and triple-negative breast cancer, and it was correlated with worse outcome in breast cancer patients. TDO2 expression was correlated with immune infiltrates and tryptophan metabolism-related genes (IDO1 and kynureninase [KYNU]). Therefore, our results indicated that TDO2 plays a pivotal role in regulating the immune microenvironment and tryptophan metabolism in breast cancer, and it predicts poor prognosis in breast cancer, which suggests that TDO2 might be a promising novel immunotherapy target for breast cancer. Additionally, we established the concept that tryptophan-catabolizing enzymes (IDO1, IDO2, TDO2, and KYNU) may function through co-regulating the immunological microenvironment, and thus immunotherapy targeting IDO1 alone might be insufficient. © 2020 The Author(s).Billions of cells undergo turnover and die via apoptosis throughout our lifetime. A prompt clearance of these apoptotic cells and debris by phagocytic cells, a process known as efferocytosis, is important in maintaining tissue homeostasis. Accordingly, impaired efferocytosis due to the defective clearance and disrupted stages can lead to a growing number of inflammation- and immune-related diseases. Although numerous studies have shown the mechanisms of efferocytosis, its role in disorders, such as non-tumor and tumor diseases, remains poorly understood. This review summarizes the processes and signal molecules in efferocytosis, and efferocytosis-related functions in non-tumor (atherosclerosis, lung diseases, etc.) and tumor diseases (breast cancer, prostate cancer, etc.), as well as describes the role of involved cytokines. Of note, there is a dual role of efferocytosis in the abovementioned disorders, and a paradoxical effect among non-tumor and tumor diseases in terms of inflammation resolution, immune response, and disease progression. Briefly, intact efferocytosis and cytokines promote tissue repair, while they contribute to tumor progression via tumor microenvironment and macrophage politzerization. Additionally, this review provides potential targets associated with TAM receptors and cytokines, such as tumor necrosis factor α - and CXCL5, suggesting potential novel therapeutic ways in treating diseases. © 2020 The Author(s).Background Asystole (ASY) and pulseless electrical activity (PEA) have a poor outcome during sudden cardiac arrest (SCA). Psychotropic medication has been associated with a risk for sudden cardiac death (SCD). Our aim was to study the association of psychotropic medication with ASY/PEA during SCA. Methods and results A total of 659 SCA subjects were derived from the emergency data of Oulu University Hospital (2007-2012). Subjects with non-cardiac origin of SCA and over 30-minute delay to rhythm recording were excluded. Population included 222 subjects after exclusions (mean age 64 ± 14 years, 78% males). Initial rhythm was ventricular fibrillation (VF) or ventricular tachycardia (VT) in 123 (55%), ASY in 67 (30%) and PEA in 32 (14%) subjects. The delay (collapse to rhythm recording) was similar in VF/VT and ASY/PEA subjects (median 8 min [1st-3rd quartile 3-12 min] versus 10 [0-14] minutes, p = 0.780). Among VF/VT subjects underlying cardiac disease was more often ischemic compared to ASY/PEA subjects (85% versus 68%, p = 0.003). Psychotropic medication was associated with ASY/PEA rhythm (OR 3.18, 95%CI 1.40-7.23, p = 0.006) after adjustment for gender, age and underlying cardiac disease. Subsequently, antipsychotics (OR 4.27, 95%CI 1.28-14.25, p = 0.018) were more common in the ASY/PEA group. selleck kinase inhibitor Benzodiazepines and antidepressants were not associated with ASY/PEA. Conclusion Psychotropic medication and especially antipsychotics are associated with non-shockable rhythm during SCA and may lower the possibility of survival from the event. This might partly explain the risk of SCD related to psychotropic medication. © 2020 The Authors.Background Several cardiopulmonary exercise test (CPET) parameters (peak VO2, PetCO2 and VE/VCO2) emerged as tools for the prediction of pulmonary arterial hypertension (PAH). Less is known on ventilatory power (VP) in patients with suspect PAH. Aim To ascertain possible correlations between VP derived at CPET and hemodynamic parameters at right heart catheterization (RHC) indicative of PH. Methods Forty-seven consecutive outpatients with suspect of PAH were assessed by CPET and RHC; VP was defined as peak SBP divided by the minute ventilation-CO2 production slope at CPET and Diastolic Pressure Gradient (DPG), Trans-pulmonary Pressure Gradient (TPG), mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR) at RHC were also assessed and compared with VP. Results VP values were inversely related to mPAP (r -0.427, p 0.003), DPG (r -0.36, p 0.019), TPG (r -0.43, p 0.004), and PVR (r -0.52, p 0.001). Correlations remained significant even after correction at multivariate analysis for age and gender. VP values below median identified subjects with mPAP ≥ 25 mmHg with an odds ratio of 4.5 (95% confidence interval 1.05-19.36, p  less then  0.05), an accuracy of 0.712 at ROC curve analysis (95% confidence interval 0.534-0.852, p  less then  0.05) and a positive predictive power 82%. Conclusions In patients with suspected PAH, VP assessed at CPET might provide further information in predicting PAH at RHC. Correlations with PVR and DPG may be helpful in differentiating patients with isolated post-capillary PH from those with combined post-capillary and pre-capillary. © 2020 The Authors.Introduction Genetic variation in the apolipoprotein E (APOE) gene is associated with Alzheimer's disease (AD) and risk factors for cardiovascular disease (CVD). DNA methylationat APOE has been associated with altered cognition and AD. It is unclear if epigenetic marks could be used for predicting future disease. Methods We assessed blood-based DNA methylation at 13 CpGs in the APOE gene in 5828 participants from the Generation Scotland (GS) cohort. Using linear mixed models regression, we examined the relationships among APOE methylation, cognition, cholesterol, the family history of AD and the risk for CVD. Results DNA methylation at two CpGs was associated with the ratio of total cholesterol and HDL cholesterol, but not with cognition, family history of AD, or the risk of CVD. Discussion APOE methylation is associated with the levels of blood cholesterol, but there is no evidence for the utility of APOE methylation as a biomarker for predicting AD or CVD. © 2020 The Authors. Alzheimer's & Dementia Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.Introduction To assess whether the incidence of dementia among immigrants in Denmark from the Faroe Islands is similar to that of the inhabitants of their new country. Methods Data on Faroese-born immigrants in Denmark were retrieved from the Danish Central Population Register. Incident dementia cases were identified from the Danish National Patient Register. Standardized incidence ratios (SIRs) were used to compare the dementia incidence in immigrants with the general Danish population. Results Female, first-generation Faroese immigrants had double the risk of dementia compared with Danes (SIR 2.1, 95% confidence interval [CI] 1.8-2.5); the excess risk prevailed even beyond 10 years in Denmark, and it affected all sub-types of dementia. In male immigrants, only a modest, statistically non-significant excess risk was seen (SIR 1.2, 95% CI 0.9-1.6). Discussion The observation of an excess risk of dementia in women only but not in men of Faroese origin living in Denmark underscores the complexity of the etiology of dementia. © 2020 The Authors. Alzheimer's & Dementia Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.Several papers have primarily considered a female disadvantage in mortality as something to explain, considering a male disadvantage to be a "natural condition". Even if, due to biological reasons, shorter life expectancy among males has been demonstrated, other factors need to be involved to explain firstly the increasing, and then the decreasing, of the male relative disadvantage over the past century. The principal aim of this paper is to provide a clearer picture of the major age-class and cause-of-death contributions to male excess mortality in England and Wales from 1881 to 2011. Results indicate a clear shift in contributions to the male disadvantage from differences occurring during the first year of life to those occurring in ageing people, and from tuberculosis, respiratory diseases, external causes and perinatal and congenital conditions to neoplasms and circulatory diseases. In contrast, the narrowing of the gap since 1981 seems to be most closely related to the decrease in the male disadvantage in respiratory diseases and to the simultaneous increasing in the female disadvantage in old-age diseases. The most important novelty of this research relates to the method instead of using ratios to investigate gender differences in health, we use decomposition methods. © 2020 The Authors.Objective We addressed three research questions (1) Are there racial mortality disparities in the adult Hispanic population that resemble those observed in the non-Hispanic population in the US? (2) Does nativity mediate the race-mortality relationship in the Hispanic population? and (3) What does the Hispanic mortality advantage relative to the non-Hispanic white population look like when Hispanic race is considered? Methods We estimated a series of parametric hazard models on eight years of mortality follow-up data and calculated life expectancy estimates using the Mortality Disparities in American Communities database. Results Hispanic white adults experience lower mortality than their Hispanic black, American Indian and Alaska Native, Some Other Race, and multiple race counterparts. This Hispanic white advantage is found mostly among the US born. The Hispanic advantage relative to the non-Hispanic white population operates for most Hispanic race groups among the foreign born but either disappears or converts to a disadvantage for most of the non-white Hispanic groups among the US born.