Sex-specific NLRP3 activation in neutrophils promotes neutrophil recruitment and NETosis in the murine model of diffuse alveolar hemorrhage.

Objectives: Diffuse alveolar hemorrhage (DAH) is a life-threatening complication of systemic lupus erythematosus and small vessel vasculitis. We previously showed that neutrophil extracellular traps (NETs) were associated with the pathogenesis of pristane-induced DAH and demonstrated that neutrophil NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome assembly participated in NET generation under sterile stimulation. We investigated whether NLRP3 inflammasome assembly in neutrophils may drive pulmonary NETosis in a mouse model of pristane-induced DAH.

Neutrophil NLRP3 promotes cardiac injury following acute myocardial infarction through IL-1β production, VWF release and NET deposition in the myocardium.

NLRP3 inflammasome has been implicated in neutrophil polarization and extrusion of neutrophil extracellular traps (NETs) in vitro and facilitates secretion of Il1-beta (IL-1β). Permanent ligation of the left anterior descending artery was used to induce MI in WT and NLRP3 mice as well as in NLRP3 recipient mice transfused with either WT or NLRP3 neutrophils. NLRP3 deficiency reduced infarct size to roughly a third of WT heart injury and preserved left ventricular (LV) function at 12 h after MI as assessed by echocardiography and triphenyltetrazolium chloride staining of live tissue.

Inhibition of protein arginine deiminase 4 prevents inflammation-mediated heart failure in arthritis.

Rheumatoid arthritis is a prototypic inflammatory condition with affected patients being at greater risk of incident heart failure (HF). Targeting innate immune cell function in the pathogenesis of HF bears the potential to guide the development of future therapies. A collagen-induced arthritis (CIA) model in DBA/1 J mice was used to generate arthritis.

Reticulated Platelets-Which Functions Have Been Established by In Vivo and In Vitro Data?

Reticulated platelets (RP) are the youngest platelet fraction released into the circulation. These immature platelets have increased RNA content, a larger cell volume, more dense granules, higher levels of surface activation markers and are thought to be more reactive compared to their mature counterparts. RP have been associated with cardiovascular disease, diabetes and increased mortality.

Active Immunoprophylaxis and Vaccine Augmentations Mediated by a Novel Plasmid DNA Formulation.

Plasmid DNA (pDNA) gene delivery is a highly versatile technology that has the potential to address a multitude of unmet medical needs. Advances in pDNA delivery to host tissue with the employment of in vivo electroporation (EP) have led to significantly enhanced gene expression and the recent demonstration of clinical efficacy with the platform. Building upon this platform, this study reports that enzyme-mediated modification of the muscle tissue extracellular matrix structure at the site of pDNA delivery operates in a synergistic manner with EP to enhance both local and systemic gene expression further.

T-cell recognition is shaped by epitope sequence conservation in the host proteome and microbiome.

Several mechanisms exist to avoid or suppress inflammatory T-cell immune responses that could prove harmful to the host due to targeting self-antigens or commensal microbes. We hypothesized that these mechanisms could become evident when comparing the immunogenicity of a peptide from a pathogen or allergen with the conservation of its sequence in the human proteome or the healthy human microbiome. Indeed, performing such comparisons on large sets of validated T-cell epitopes, we found that epitopes that are similar with self-antigens above a certain threshold showed lower immunogenicity, presumably as a result of negative selection of T cells capable of recognizing such peptides.

Hyaluronan breakdown contributes to immune defense against group A Streptococcus.

Group A Streptococcus (GAS) commonly infects human skin and occasionally causes severe and life-threatening invasive diseases. The hyaluronan (HA) capsule of GAS has been proposed to protect GAS from host defense by mimicking endogenous HA, a large and abundant glycosaminoglycan in the skin. However, HA is degraded during tissue injury, and the functions of short-chain HA that is generated during infection have not been studied.

Structure and function of the human skin microbiome.

An abundant and diverse collection of bacteria, fungi, and viruses inhabits the human skin. These microorganisms vary between individuals and between different sites on the skin. The factors responsible for the unique variability of the skin microbiome are only partly understood, but results suggest that host genetic and environmental influences play a major role.

Staphylococcus epidermidis uses distinct mechanisms of biofilm formation to interfere with phagocytosis and activation of mouse macrophage-like cells 774A.1.

Assembly of adherent biofilms is the key mechanism involved in Staphylococcus epidermidis virulence during device-associated infections. Aside from polysaccharide intercellular adhesin (PIA), the accumulation-associated protein Aap and the extracellular matrix binding protein Embp act as intercellular adhesins, mediating S. epidermidis cell aggregation and biofilm accumulation.

Aripiprazole as adjunct to a mood stabilizer and citalopram in bipolar depression: a randomized placebo-controlled pilot study.

Objective: The use of atypical antipsychotics (AAPs) for the treatment of unipolar and bipolar depression has been more and more frequently evaluated, and aripiprazole showed positive effects in the treatment of unipolar depression. However, no placebo-controlled studies of adjunctive aripiprazole for the treatment of bipolar depression have been performed yet.

Methods: In this prospective, double-blind, placebo-controlled, randomized trial, 23 inpatients with bipolar depression according to DSM-IV criteria were included.

The giant extracellular matrix-binding protein of Staphylococcus epidermidis mediates biofilm accumulation and attachment to fibronectin.

Virulence of nosocomial pathogen Staphylococcus epidermidis is essentially related to formation of adherent biofilms, assembled by bacterial attachment to an artificial surface and subsequent production of a matrix that mediates interbacterial adhesion. Growing evidence supports the idea that proteins are functionally involved in S. epidermidis biofilm accumulation.

Clonidine improves hyperarousal in borderline personality disorder with or without comorbid posttraumatic stress disorder: a randomized, double-blind, placebo-controlled trial.

The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition borderline personality disorder (BPD) seems to constitute a very heterogeneous category. Therefore, pharmacological therapy is symptom-oriented or targets comorbid conditions. A high comorbidity exists between BPD and posttraumatic stress disorder (PTSD).

Acute HPA axis responses, heart rate, and mood changes to psychosocial stress (TSST) in humans at different times of day.

There is evidence showing that HPA axis responses to pharmacological provocation depend on time of day with larger cortisol responses in the afternoon and evening compared to the morning hours. However, it is still unknown whether HPA axis responses to psychological stress are affected by time of day and whether they can be assessed with equal reliability in the morning and afternoon, respectively. The present reanalysis is based on five independent studies conducted in the same laboratory by and.

Dissociation between reactivity of the hypothalamus-pituitary-adrenal axis and the sympathetic-adrenal-medullary system to repeated psychosocial stress.

Objective: This study investigated endocrine and autonomic stress responses after repeated psychosocial stress. A first goal of the study was to investigate whether peripheral catecholamines and cardiovascular parameters would show similar or different habituation patterns after repeated stress. The second aim was to detect possible subgroups with regard to individual habituation patterns in the hypothalamus-pituitary-adrenal (HPA) axis and monitor their respective sympathetic stress responses.

The cortisol awakening response - normal values and confounds.

In several recent investigations it could be demonstrated that the free cortisol response to awakening can serve as an useful index of the adrenocortical activity. When measured with strict reference to the time of awakening the assessment of this endocrine response is able to uncover subtle changes in hypothalamus-pituitary-adrenal (HPA) axis activity, which are, for instance, related to persisting pain, burnout and chronic stress. Furthermore, it has been suggested that the HPA axis might serve as an indicator of allostatic load in subjects exposed to prolonged environmental noise.

Moderate psychosocial stress appears not to impair recall of words learned 4 weeks prior to stress exposure.

Recent studies in humans have reported that recall of previously learned material is especially sensitive to the disruptive effects of pharmacologically induced cortisol elevations. Whether similar effects occur after exposure to psychosocial stress remains to be shown. Moreover it is unknown whether stress before or after the initial learning interacts with the later effects of repeated stress on delayed recall (e.

Sex differences in glucocorticoid sensitivity of proinflammatory cytokine production after psychosocial stress.

Objective: Men and women show marked differences in susceptibility to disorders related to the immune system. These gender differences have been proposed to be mediated by functional interactions of the hypothalamus-pituitary-adrenal (HPA) and hypothalamus-pituitary-gonadal (HPG) axes. A potential mechanism involved in this interaction is the glucocorticoid (GC) sensitivity of relevant target tissues for GC.

The relationship between stress induced cortisol levels and memory differs between men and women.

Epidemiological as well as experimental studies in elderly subjects have suggested that postmenopausal women are more susceptible to the memory impairing effects of elevated cortisol levels than elderly men. Little is known however about gender differences in the susceptibility to acute stress in young subjects. In the present study a total of 58 healthy young subjects learned a word list, with recall being tested after a brief distraction task.

No evidence for a close relationship between personality traits and circadian cortisol rhythm or a single cortisol stress response.

Personality traits measured with the Eysenck Personality Questionnaire-Revised did not show associations with basal or stimulated concentrations of cortisol in a sample of 81 subjects. Cortisol responses to a single exposure to psychosocial stress as well as circadian salivary-free cortisol patterns did not distinguish between subjects with high or low scores on Extraversion, Neuroticism, or Psychoticism, respectively.

Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis.

Objective: Results from animal and human studies suggest that disregulations of the hypothalamus-pituitary-adrenal (HPA) axis are involved in several behavioral, circulatory, endocrine, and immune disorders with clear-cut gender differences in disease prevalence. The aim of the present study was to investigate sex-specific HPA response patterns with a focus on the contribution of gonadal steroids as possible mediators.

Methods: A total of 81 healthy adults were investigated in the present study.

Increasing correlations between personality traits and cortisol stress responses obtained by data aggregation.

Attempts to link personality traits and cortisol stress responses have often been inconclusive. The aim of this paper was to investigate this association by aggregating cortisol stress responses. Therefore, 20 healthy men were exposed to a task consisting of public speaking and mental arithmetics in front of an audience on five days.

Short-term estradiol treatment enhances pituitary-adrenal axis and sympathetic responses to psychosocial stress in healthy young men.

Evidence from animal studies and clinical observations suggest that the activity of the pituitary-adrenal axis is under significant influence of sex steroids. The present study investigated how a short term elevation of estradiol levels affects ACTH, cortisol, norepinephrine, and heart rate responses to mental stress in healthy men. In a double blind study, 16 men received a patch delivering 0.