The Tumor Metabolite 5'-Deoxy-5'Methylthioadenosine (MTA) Inhibits Maturation and T Cell-Stimulating Capacity of Dendritic Cells.

Metabolite accumulation in the tumor microenvironment fosters immune evasion and limits the efficiency of immunotherapeutic approaches. Methylthioadenosine phosphorylase (MTAP), which catalyzes the degradation of 5'-deoxy-5'methylthioadenosine (MTA), is downregulated in many cancer entities. Consequently, MTA accumulates in the microenvironment of MTAP-deficient tumors, where it is known to inhibit tumor-infiltrating T cells and NK cells.

Psychological and physiological health outcomes of virtual reality-based mindfulness interventions: A systematic review and evidence mapping of empirical studies.

Objective: In the past two decades, mindfulness, rooted in Buddhist traditions, has gained considerable scientific interest. Virtual reality (VR) technology, in particular head-mounted displays, offers immersive experiences and is examined in this systematic review in terms of VR-based mindfulness interventions and their effects on psychological and physiological health outcomes.

Methods: Using the Preferred Reporting Items for Systematic Review and Meta Analyses guidelines, a systematic search was conducted with the following search terms: [(mindful* OR "meditat*") AND ("virtual reality" OR "VR") AND (health OR physio* OR psycho* OR mental OR physical)].

[Impact of Critical Events During Deployments on the Mental Health of Military Personnel].

Introduction: Deployments abroad pose an occupational risk for mental disorders and reduced quality of life among military personnel. This study examines the question of whether a relevant predictor for the frequency of mental disorders after deployments abroad can be found. It is postulated that soldiers who experience a military-specific critical event develop more symptoms and their quality of life decreases.

Sex-Dependent T Cell Dysregulation in Mice with Diet-Induced Obesity.

Obesity is an emerging public health problem. Chronic low-grade inflammation is considered a major promotor of obesity-induced secondary diseases such as cardiovascular and fatty liver disease, type 2 diabetes mellitus, and several cancer entities. Most preliminary studies on obesity-induced immune responses have been conducted in male rodents.

Impact of life-threatening military incidents during deployments abroad on the relationships between military personnel and their families.

Introduction: The influence of deployments on family relationships has hardly been investigated. Following a recently proposed new research strategy, military personnel with and without deployment-related life-threatening military incidents during deployment were compared. The hypothesis was that partner and family relationships of military personnel who experienced such an event would deteriorate more.

Incidence of mental disorders in soldiers deployed to Afghanistan who have or have not experienced a life-threatening military incident-a quasi-experimental cohort study.

Introduction: There is very good international research on deployment-related mental disorders in military personnel. The incidence rates show a very wide range. A new strategy is therefore proposed in order to achieve better standardization and thus better comparability of the studies.

Strain specific differences in vitamin D3 response: impact on gut homeostasis.

Vitamin D3 regulates a variety of biological processes irrespective of its well-known importance for calcium metabolism. Epidemiological and animal studies indicate a role in immune regulation, intestinal barrier function and microbiome diversity. Here, we analyzed the impact of different vitamin D3- containing diets on C57BL/6 and BALB/c mice, with a particular focus on gut homeostasis and also investigated effects on immune cells .

D-2-hydroxyglutarate supports a tolerogenic phenotype with lowered major histocompatibility class II expression in non-malignant dendritic cells and acute myeloid leukemia cells.

D-2-hydroxyglutarate (D-2-HG) accumulates in patients with acute myeloid leukemia (AML) with mutated isocitrate dehydrogenase (IDH) and in other malignancies. D-2-HG suppresses antitumor T-cell immunity but little is known about potential effects on non-malignant myeloid cells. Here we show that D-2-HG impairs human but not murine dendritic cell differentiation, resulting in a tolerogenic phenotype with low major histocompatibility class II expression.

MCT4 blockade increases the efficacy of immune checkpoint blockade.

Background & Aims: Intratumoral lactate accumulation and acidosis impair T-cell function and antitumor immunity. Interestingly, expression of the lactate transporter monocarboxylate transporter (MCT) 4, but not MCT1, turned out to be prognostic for the survival of patients with rectal cancer, indicating that single MCT4 blockade might be a promising strategy to overcome glycolysis-related therapy resistance.

Methods: To determine whether blockade of MCT4 alone is sufficient to improve the efficacy of immune checkpoint blockade (ICB) therapy, we examined the effects of the selective MCT1 inhibitor AZD3965 and a novel MCT4 inhibitor in a colorectal carcinoma (CRC) tumor spheroid model co-cultured with blood leukocytes in vitro and the MC38 murine CRC model in vivo in combination with an antibody against programmed cell death ligand-1(PD-L1).

Can Exercise Enhance the Efficacy of Checkpoint Inhibition by Modulating Anti-Tumor Immunity?

Immune checkpoint inhibition (ICI) has revolutionized cancer therapy. However, response to ICI is often limited to selected subsets of patients or not durable. Tumors that are non-responsive to checkpoint inhibition are characterized by low anti-tumoral immune cell infiltration and a highly immunosuppressive tumor microenvironment.

Targeting the microenvironment in the treatment of arteriovenous malformations.

Extracranial arteriovenous malformations (AVMs) are regarded as rare diseases and are prone to complications such as pain, bleeding, relentless growth, and high volume of shunted blood. Due to the high vascular pressure endothelial cells of AVMs are exposed to mechanical stress. To control symptoms and lesion growth pharmacological treatment strategies are urgently needed in addition to surgery and interventional radiology.

Age and gender differences in narcissism: A comprehensive study across eight measures and over 250,000 participants.

Age and gender differences in narcissism have been studied often. However, considering the rich history of narcissism research accompanied by its diverging conceptualizations, little is known about age and gender differences across various narcissism measures. The present study investigated age and gender differences and their interactions across eight widely used narcissism instruments (i.

Prior stress and vasopressin promote corticotropin-releasing factor inhibition of serotonin release in the central nucleus of the amygdala.

Corticotropin-releasing factor (CRF) is essential for coordinating endocrine and neural responses to stress, frequently facilitated by vasopressin (AVP). Previous work has linked CRF hypersecretion, binding site changes, and dysfunctional serotonergic transmission with anxiety and affective disorders, including clinical depression. Crucially, CRF can alter serotonergic activity.

Acidity-mediated induction of FoxP3 regulatory T cells.

Glucose limitation and increased lactic acid levels are consequences of the elevated glycolytic activity of tumor cells, and constitute a metabolic barrier for the function of tumor infiltrating effector immune cells. The immune-suppressive functions of regulatory T cells (Tregs) are unobstructed in lactic-acid rich environments. However, the impact of lactic acid on the induction of Tregs remains unknown.

Low-density lipoprotein balances T cell metabolism and enhances response to anti-PD-1 blockade in a HCT116 spheroid model.

Introduction: The discovery of immune checkpoints and the development of their specific inhibitors was acclaimed as a major breakthrough in cancer therapy. However, only a limited patient cohort shows sufficient response to therapy. Hence, there is a need for identifying new checkpoints and predictive biomarkers with the objective of overcoming immune escape and resistance to treatment.

Glutamine synthetase expression rescues human dendritic cell survival in a glutamine-deprived environment.

Introduction: Glutamine deficiency is a well-known feature of the tumor environment. Here we analyzed the impact of glutamine deprivation on human myeloid cell survival and function.

Methods: Different types of myeloid cells were cultured in the absence or presence of glutamine and/or with L-methionine-S-sulfoximine (MSO), an irreversible glutamine synthetase (GS) inhibitor.

Expression of pH-Sensitive TRPC4 in Common Skin Tumors.

TRPCs (transient receptor potential classical or cation channels) play a crucial role in tumor biology, especially in the Ca homeostasis in cancer cells. TRPC4 is a pH-sensitive member of this family of proteins. As solid tumors exhibit an inversed pH-gradient with lowered extracellular and increased intracellular pH, both contributing to tumor progression, TRPC4 might be a signaling molecule in the altered tumor microenvironment.

Targeting lactate metabolism for cancer immunotherapy - a matter of precision.

Immune checkpoint inhibitors and adoptive T cell therapies have been valuable additions to the toolbox in the fight against cancer. These treatments have profoundly increased the number of patients with a realistic perspective toward a return to a cancer-free life. Yet, in a number of patients and tumor entities, cancer immunotherapies have been ineffective so far.

Chronic administration of glucocorticoid receptor ligands increases anxiety-like behavior and selectively increase serotonin transporters in the ventral hippocampus.

Organic cation transporter-3 (OCT3) is widely distributed in the brain with high expression in portions of the stress axis. These high capacity, polyspecific transporters function in monoamine clearance and are sensitive to the stress hormone corticosterone. In rats, withdrawal from chronic amphetamine increases OCT3 expression in specific limbic brain regions involved anxiety and stress responses, including the ventral hippocampus, central nucleus of amygdala (CeA) and dorsomedial hypothalamus.

Metabolic Heterogeneity of Brain Tumor Cells of Proneural and Mesenchymal Origin.

Brain-tumor-initiating cells (BTICs) of proneural and mesenchymal origin contribute to the highly malignant phenotype of glioblastoma (GB) and resistance to current therapies. BTICs of different subtypes were challenged with oxidative phosphorylation (OXPHOS) inhibition with metformin to assess the differential effects of metabolic intervention on key resistance features. Whereas mesenchymal BTICs varied according to their invasiveness, they were in general more glycolytic and less responsive to metformin.

Predicting post-total ankle arthroplasty walking speed based on preoperative gait mechanics.

Decreased walking speed is associated with impaired physical performance and function in older adults. Following total ankle arthroplasty (TAA), walking speed continues to be slower than age matched controls. The purpose of this study was to determine if patients 1 year post-TAA can achieve walking speed benchmarks and investigate if gait metrics are predictive of achieved benchmarks.

Tachycardiomyopathy entails a dysfunctional pattern of interrelated mitochondrial functions.

Tachycardiomyopathy is characterised by reversible left ventricular dysfunction, provoked by rapid ventricular rate. While the knowledge of mitochondria advanced in most cardiomyopathies, mitochondrial functions await elucidation in tachycardiomyopathy. Pacemakers were implanted in 61 rabbits.

Individual and Organizational Factors in Coping With COVID-19 in Soldier Students.

The COVID-19 pandemic has posed significant burden across different industrial sectors. Generally, an increase in psychological stress experiences has been reported, while the stress and coping responses of specific, potentially burdened populations have received less attention thus far. Thus, the present study investigated relations between individual (i.

Psychometric Properties of the Mindfulness Inventory for Sport (German Version).

Mindfulness-based training programs are highly established in competitive and recreational sports. One of the best-known approaches is the Mindfulness-Acceptance-Commitment Approach (MAC) by Gardner and Moore), which integrates mindfulness aspects of awareness, non-judgmental attitude, and focus. Based on these aspects, Thienot and colleagues developed and validated an English language sport-specific questionnaire, the so-called Mindfulness Inventory for Sport (MIS), for the assessment of mindfulness skills in athletes.