Mechanisms Of Chronic Stress Research Articles

Chronic stress promotes gastric cancer progression via the adrenoceptor beta 2/PlexinA1 pathway.

Chronic stress is a common emotional disorder in cancer patients. Chronic stress promotes progression of gastric cancer (GC) and leads to poor outcomes. However, the underlying mechanisms remain not clear. Herein, we explored the possible mechanisms of chronic stress in GC progression. The Cancer Genome Atlas (TCGA) datasets were analyzed for differentially expressed genes. Clinical data of GC were evaluated for their association with PlexinA1 using TCGAand Kaplan-Meier-plotter databases. Chronic stress of GC patients was evaluated using the Self-Rating Anxiety Scale and Self-Rating Depression Scale. Chronic unpredictable mild stress (CUMS) was used to induce chronic stress in mice. Gastric xenograft tumor was constructed using the sewing method. Chronic stress-like behaviors were assessed using light/dark box and tail suspension tests. Protein expression was detected using immunohistochemistry and Western blot analysis. Analyses of TCGA and the Kaplan-Meier-plotter databases showed that patients with high levels of PlexinA1 in GC had worse overall survival than those with low levels of PlexinA1. A total of 36 GC patients were enrolled in the study, and about 33% of the patients had chronic stress. Compared with patients without chronic stress, higher expression levels of adrenoceptor beta 2 and PlexinA1 were observed in patients with chronic stress. The tumor size in mice under CUMS was significantly increased compared with the control mice. Adrenoceptor beta 2, PlexinA1, N-cadherin, and alpha-smooth muscle actin, as well as Ki67 were highly expressed in the tumors of CUMS group. However, E-cadherin was lowly expressed in the tumors of CUMS group. Importantly, chemical sympathectomy with 6-hydroxydopamineor treatment with a selective β2 adrenergic receptor antagonist (ICI118,551) could reverse these effects. Our findings suggest that chronic stress plays an important role in GC progression and there is a potential for blocking the epinephrine-β2AR/PlexinA1 pathway in the treatment of GC.

Cadmium exposure-induced rat testicular dysfunction and its mechanism of chronic stress

Cadmium is a common environmental pollutant in daily life, the toxic mechanisms of chronic cadmium exposure on the testes have not been fully elucidated. This study aimed to explore the effects of cadmium exposure on male reproductive health and its mechanism. The results showed that cadmium exposure led widened interstitial spaces, abnormal seminiferous tubule morphology, and decreased Leydig cell numbers. Moreover, sperm quality was significantly reduced, along with a decrease in fertility rate. And cadmium exposure could activate the hypothalamic-pituitary-adrenal (HPA) axis, elevate blood glucocorticoid levels, subsequently increase glucocorticoid receptor (GR) expression and activation in testicular Leydig cells.Then GR act on the glucocorticoid receptor element (GRE) in the DNA methyltransferase 3 A (DNMT3A) promoter region and upregulate DNMT3A expression. Consequently, this led to an increase in DNA methylation levels in the angiotensin II receptor 2 (AT2R) promoter region, resulting in reduced AT2R expression and inhibiting testicular steroidogenesis. This study systematically elucidated that cadmium exposure could lead to testicular steroidogenesis suppression and decreased fertility through the GR/DNMT3A/AT2R signaling pathway. This research further provides theoretical and experimental evidence for confirming the threat of cadmium exposure to human reproduction, and contributes to the guidance and protection of male reproductive health.

Establishment of insomnia model of chronic unpredictable stress in rats

It is well known that stressful situation is one of the important factors causing insomnia, however, the underlying mechanism is still elusive. Therefore, the establishment of a suitable animal model of stress insomnia will be of great help to solve this problem. In this study, by combining with chronic unpredictable stress (multitude of stressors) and sleep deprivation, we attempted to establish a rat model of stress insomnia. It was observed that rats with stress insomnia showed significant weight loss, and less sleep quality in pentobarbital sodium induced sleep test and electroencephalogram detection. Moreover, rats with stress insomnia showed greater depression and anxiety detected by forced swimming, sucrose preference test and open field. Since oxidative stress has been reported to be involved in insomnia, we further evaluated the production of oxidative stress and found that the levels of lipid peroxidation product malondialdehyde (MDA) in liver, serum total bilirubin and urine biopyrrin were all significantly increased in rats with stress insomnia. In addition, we also found that the memory of these rats with stress insomnia was also obviously reduced in water maze. Taken together, these results demonstrate that the emotional behaviors, memory, oxidative and metabolism of the rats were all significantly changed after modeling, indicating a rat model of stress insomnia was successful establishment, and this animal model will provide basis to further explore the underlying mechanism of chronic stress in insomnia.

Hyperbaric oxygen improves depression-like behaviors in chronic stress model mice by remodeling gut microbiota and regulating host metabolism.

There is growing evidence that the gut microbiota plays a significant part in the pathophysiology of chronic stress. The dysbiosis of the gut microbiota closely relates to dysregulation of microbiota-host cometabolism. Composition changes in the gut microbiota related to perturbations in metabolic profiles are vital risk factors for disease development. Hyperbaric oxygen therapy is commonly applied as an alternative or primary therapy for various diseases. Therefore, a metabolic and gut bacteria perspective is essential to uncover possible mechanisms of chronic stress and the therapeutic effect of hyperbaric oxygenation. We determined that there were significantly disturbed metabolites and disordered gut microbiota between control and chronic stress group. The study aims to offer further information on the interactions between host metabolism, gut microbiota, and chronic stress. At present, chronic unpredictable mild stress is considered the most widespread method of modeling chronic stress in animals, so we used a chronic unpredictable mild stress mouse model to characterize changes in the metabolome and microbiome of depressed mice by combining 16S rRNA gene sequencing and UHPLC-MS/MS-based metabolomics. Pearson's correlation-based clustering analysis was performed with above metabolomics and fecal microbiome data to determine gut microbiota-associated metabolites. We found that 18 metabolites showed a significant correlation with campylobacterota. Campylobacterota associated metabolites were significantly enriched mainly in the d-glutamate and d-glutamine metabolism. Hyperoxia treatment may improve depression-like behaviors in chronic stress model mice through regulating the disrupted metabolites. Hyperbaric oxygen improves depression-like behaviors in chronic stress model mice by remodeling Campylobacterota associated metabolites.

Stress and cancer: The mechanisms of immune dysregulation and management.

Advances in the understanding of psychoneuroimmunology in the past decade have emphasized the notion that stress and cancer are interlinked closely. Durable chronic stress accelerated tumorigenesis and progression, which is unfavorable for clinical outcomes of cancer patients. Available evidence has provided unprecedented knowledge about the role and mechanisms of chronic stress in carcinogenesis, the most well-known one is dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system (SNS). With abnormal activation of neuroendocrine system, stress-related hormones contribute to increased oncogenes expression, exacerbated chronic inflammation and impaired immunologic function. In addition, accumulating studies have demonstrated that diverse stress interventions including pharmacological approaches, physical exercises and psychological relaxation have been administered to assist in mental disorders reduction and life quality improvement in cancer patients. In this review, we systematically summarize the connection and mechanisms in the stress-immune-cancer axis identified by animal and clinical studies, as well as conclude the effectiveness and deficiencies of existing stress management strategies.

Chronic Stress Activates PlexinA1/VEGFR2-JAK2-STAT3 in Vascular Endothelial Cells to Promote Angiogenesis.

It is known that chronic stress modulates multiple processes in a complex microenvironment, such as angiogenesis and immune function. However, the role of chronic stress inducing tumor angiogenesis and how it contributes to tumor progression are not quite clear. The following study assess psychological state from numerous ambulatory cancer cases (n=332), and chronic stress-related hormone levels were further measured. Here, we show that chronic stress not only causes behavioral changes in human, most importantly attributed to an elevated level of stress-related hormones. To address this, isoprenaline, the agonist of β2-adrenergic receptor (β2-AR), was utilized for simulating chronic stress and demonstrating the mechanism of stress in tumor angiogenesis at molecular level both in vivo and in vitro. As suggested by this study, isoprenaline promote VEGF autocrine of HUVECs, which can induce plexinA1 and VEGFR2 expression. Moreover, we show that isoprenaline promoted the expression of p-JAK2 and p-STAT3 in vitro. The results reveal that, isoprenaline enhances the autocrine of VEGF in HUVECs and up-regulating plexinA1 and VEGFR2 levels, thus activating the phosphorylation of JAK2-STAT3 pathway, the two essential parts during angiogenesis. The present work indicates that, the mechanism of chronic stress in enhancing angiogenesis is probably achieved through activating the plexinA1/VEGFR2-JAK2-STAT3 signal transduction pathway within HUVECs, and this is probably a candidate target for developing a strategy against angiogenesis in cancer.

Architectural Interventions to Mitigate Occupational Stress Among Office Workers

Stress is one issue that affects the health and well-being of every building occupant. The negative effects of stress are more pronounced in workplaces, where stress can act as a major agent of disease and an impediment to employee productivity and satisfaction. The underlying causes of occupational stress are varied and include job insecurity, extended hours, excessive workload, altercations within the organization, tight deadlines, changes in responsibilities, and lack of autonomy, among others. One of the factors that can contribute to overall occupational stress is the working environment itself—a factor that can be mitigated by design. While occupational stress may arise from a multiplicity of causes, designers have numerous interventions they can employ to decrease it.
 The literature on occupational health, well-being, satisfaction, and productivity is broad and multifaceted; however, this paper is limited to exploring stress factors that correlate with the built environment and focuses on employees who are experiencing a high rate of stress in office buildings as the target group. To address these issues, supporting literature was explored to identify environmental interventions that could reduce stress or enhance the stress-coping abilities of workers in offices by improving the environmental quality of the built environment.
 This article explores the following questions: How does space cause people to experience mental stress? In what ways can the built environment itself be a generator of stress? What are the main environmental factors in offices that can mitigate the stress levels of employees or help them to recover more easily from work-related stress? To answer these questions, it is necessary to understand the causes and mechanisms of chronic stress, including work-related stressors, and to identify the factors in the built environment that can be associated with occupational stress. The present paper is based on concurrent analyses of supporting literature in the rather different fields of architecture, public health, psychology, management, and environmental studies. The outcome is an identified set of practical strategies that provide solutions for healthier and more productive workplaces. By concentrating on measures that can reduce employee stress levels, these strategies can be used as a source for evidence-based workplace designs.

The relationship between chronic stress and tumor

The relationship between chronic stress caused by fast-paced lifestyle and tumor has been widely concerned. A large number of epidemiological and clinical studies have found that long-term depression, anxiety, depression and chronic stress state, such as social isolation can significantly affect the neuroendocrine system, immune system and the composition and function of the gut microbiota, then produce inflammation as well as a variety of antitumor drug resistance, which are closely related to the proliferation, metastasis and treatment of tumor. Effective stress management and personalized approaches to cancer prevention and treatment are critical. In this review, the effects and mechanisms of chronic stress on tumors are summarized as follows. Key words: Chronic stress; Neuroendocrine system; Immune system; Gut microbiota; Antitumor drug resistance; Tumor

Chronic stress: a critical risk factor for atherosclerosis.

Chronic stress refers to the non-specific systemic reaction that occurs when the body is stimulated by various internal and external negative factors over a long time. The physiological response to chronic stress exposure has long been recognized as a potent modulator in the occurrence of atherosclerosis. Furthermore, research has confirmed the correlation between atherosclerosis and cardiovascular events. Chronic stress is pervasive during negative life events and may lead to the formation of plaque. Several epidemiological studies have shown that chronic stress is an independent risk factor for the development of vascular disease and for increased morbidity and mortality in patients with pre-existing coronary artery disease. One possible mechanism for this process is that chronic stress causes endothelial injury, directly activating macrophages, promoting foam cell formation and generating the formation of atherosclerotic plaque. This mechanism involves numerous variables, including inflammation, signal pathways, lipid metabolism and endothelial function. The mechanism of chronic stress in atherosclerosis should be further investigated to provide a theoretical basis for efforts to eliminate the effect of chronic stress on the cardiocerebral vascular system.

A pharmacological approach towards mechanisms Of chronic stress inducing neuroinflammation, Depression and cognitive impairment.

A pharmacological approach towards mechanisms Of chronic stress inducing neuroinflammation, Depression and cognitive impairment.

A pharmacological approach towards mechanisms Of chronic stress inducing neuroinflammation, Depression and cognitive impairment

A pharmacological approach towards mechanisms Of chronic stress inducing neuroinflammation, Depression and cognitive impairment

December 2015 - This Month in JoVE: Flu Surveillance in Swine, DNA Nanorobots, Analyzing Crude Oil, and a Translational Model of Depression

Here's a look at what's coming up in the December 2015 issue of JoVE: The Journal of Visualized Experiments. In JoVE Immunology & Infection, we know that the peak of flu season is on its way-and because pigs are important hosts for the influenza A virus, it is critical to monitor virus evolution in swine populations to get a snapshot of current circulating strains. Nasal swabs are a gold-standard technique for taking diagnostic samples from live pigs, but it requires restraining the pigs. Nolting et al. present an alternative sampling method using nasal wipes, which involves rubbing a piece of fabric across the snout of the pig with minimal to no restraint of the animal. The nasal wipe procedure is simple to perform, and virus detection and isolation rates are adequate to make it a viable and low-stress sampling method for flu in pigs. In JoVE Chemistry, DNA nanorobots are hollow hexagonal nanodevices that open in response to specific stimuli to present the cargo sequestered inside. This month, Amir et al. describe a nanorobot fabrication protocol that uses the DNA origami technique. This involves mixing short single-stranded DNA staples with long, circular, single-stranded DNA scaffolds. In a standard thermocycler, the staples anneal to the scaffolds, thus driving the folding of the nanorobot. After the folding reaction is complete, agarose gel electrophoresis (AGE) is used to visualize and estimate the purity of the DNA nanorobots. Finally, nanorobot fabrication is verified by transmission electron microscopy (TEM). This procedure allows for the construction of complex 2D/3D nano-architecture. In JoVE Environment, crude oil is one of the most valuable natural resources because it is the raw material for many fuels and chemical products. Accurate analysis of crude oil, especially the content of highly toxic hydrogen sulfide (H2S), is essential for developing and implementing safety measures in the event of a release or spill. Heshka and Hager present a multidimensional gas chromatography method for analyzing dissolved hydrogen sulfide in crude oil samples. As far as we know, this is the only method that can accurately measure dissolved hydrogen sulfide in heavy crudes, without the use of sub-ambient cooling. In JoVE Behavior, Frisbee et al. present one of the most useful models for studying the pathophysiology of depression in rodents. This protocol uses a variety of mild stressors, and after a period of exposure to unpredictable chronic mild stress, rodents develop behaviors and cardiovascular alterations that are comparable to the symptoms of clinical depression. This approach allows for detailed studies of the pathological mechanisms of chronic stress, and can be used to test new therapies and interventions for chronic stress-induced depression. You've just had a sneak peek of the December 2015 issue of JoVE. Visit the website to see the full-length articles, plus many more, in JoVE: The Journal of Visualized Experiments.

Chronic stress promotes the progression of pressure overload-induced cardiac dysfunction through inducing more apoptosis and fibrosis.

Stress serves as a risk factor in the etiology of hypertension. The present study was designed to decipher the effect and mechanism of chronic stress on the progression of pressure overload-induced cardiac dysfunction. We used abdominal aortic constriction (AAC) to induce pressure overload with or without chronic restraint stress to establish the animal models. Echocardiographic analysis showed pressure overload-induced cardiac dysfunction was worsened by chronic stress. Compared with the AAC rats, there is a significant increase in cardiac hypertrophy, injury, apoptosis and fibrosis of the AAC + stress rats. Furthermore, we found the secretion of norepinephrine (NE) increased after the AAC operation, while the level of NE was higher in the AAC + stress group. Cardiomyocytes and cardiac fibroblasts isolated from neonatal rats were cultured and separately treated with 1, 10, 100 microM NE. The higher concentration NE induced more cardiomyocytes hypertrophy and apoptosis, cardiac fibroblasts proliferation and collagen expression. These results revealed that high level of NE-induced cardiomyocytes hypertrophy and apoptosis, cardiac fibroblasts proliferation and collagen expression further contributes to the effect of chronic stress on acceleration of pressure overload-induced cardiac dysfunction.

EPA-0163 – The adverse children experience in sjogren's syndrome adult patients suffering mental disorders

Introduction The adverse experience in childhood (parental deprivation mostly) (AEC) has an important role in predisposing to mood and immuno-inflammatory rheumatic disorders in adults via chronic stress mechanisms. The primary Sjogren's Syndrome (SS) - a chronic, systemic autoimmune disease, which has some common pathogenic links with stress-related mental disorders. Objectives/Aims To evaluate the AEC and MD presentation in SS patients. Methods 80 inpatients (mean age 46,2+12,3 yrs) suffering SS were enrolled in the study. MD were diagnosed in accordance with ICD-10 criteria. The severity of depression, anxiety, stress were measured with HADS, MADRS, HAM-A, PSS-10. Results The AEC had 78,7% of SS patients (recurrent events – 32,5%). Patients with AEC had an increased risk of developing dysthymia (OR=1,34; 95% CI=0,26–6,83) and depressive episode (OR=1,75 (0,35–8,65)) in adults. Recurrent depression was not revealed in patients with ACE. However, patients with AEC had no reliable differences in the MADRS, HAM-A, HADS, PSS-10 compared to patients without AEC. Patients with AEC had an increased risk of suicide attempts (OR=2,15; (0,25–37,2)) and suicidal thoughts (OR=4,58; (0,25–18,5)). The reliable correlations of the severity of SS symptoms (dry eyes/mouth, lymphoma) and AEC have not been confirmed. Patients with AEC had early onset SS (33,6±13,0 vs 38,1±14,2) and MD (28,4±12,6 vs 34,1±13,5) than patients without AEC. Conclusion AE? is a significant risk factor for depression and suicidal thoughts and attempts in patients suffering SS.

Increased concentration of beta-endorphin in the sera of patients with severe atopic dermatitis.

Serum beta-endorphin was measured by radioimmunoassay in 25 patients with atopic dermatitis and 100 healthy subjects. The neuropeptide was found to be markedly (p < 0.001) increased in patients with atopic dermatitis (9.2 +/- 3.4 pg/ml) as compared to normal controls (6.1 +/- 1.5 pg/ml). A correlation between increased serum beta-endorphin concentration and some clinical parameters of the disease has been found. The statistically significant elevation of beta-endorphin was found in patients with widespread atopic dermatitis lesions involving more than 20% of the skin surface (11.1 +/- 3.6 pg/ml), a high disease severity score (10.7 +/- 3.7 pg/ml), and previous bronchial asthma symptoms (11.6 +/- 3.1 pg/ml). A possible explanation of increased beta-endorphin is either its generation in atopic dermatitis lesions by inflammatory cells or activation of pituitary-adrenal axis by psychoneural factors in the mechanism of chronic stress.