Quercetin inhibits platelet activation and ER-stress mediated autophagy in response to extracellular histone.

Background: Cellular histones are DNA-binding nuclear proteins involved in chromatin remodelling and regulation of gene expression. However, extracellular histones act as damage-associated molecular patterns (DAMPs) and contribute to multiorgan damage in conditions with sepsis and diseases with acute critical illnesses. Alongside, histones are associated with thrombocytopenia due to dysfunctional platelets that regulate hemostasis and thrombosis.

Counteraction of unconjugated bilirubin against heme-induced toxicity in platelets.

Platelets are essential for normal hemostasis and thrombosis but become hyperactive in hemolytic disorders. Cell-free heme is known to be toxic to platelets and endothelial cells, playing a significant role in the progression of pathological complications in various hemolytic conditions. The abnormal activation of circulatory platelets results in micro/macrovascular thrombosis and clot formation in the lungs, worsening the disease.

Human Host Defense Peptide LL-37 Suppresses TNFα-Mediated Matrix Metalloproteinases MMP9 and MMP13 in Human Bronchial Epithelial Cells.

Introduction: TNFα-inducible matrix metalloproteinases play a critical role in the process of airway remodeling in respiratory inflammatory disease including asthma. The cationic host defense peptide LL-37 is elevated in the lungs during airway inflammation. However, the impact of LL-37 on TNFα-driven processes is not well understood.

Concentration-dependent alterations in the human plasma proteome following controlled exposure to diesel exhaust.

Traffic-related air pollution (TRAP) exposure is associated with systemic health effects, which can be studied using blood-based markers. Although we have previously shown that high TRAP concentrations alter the plasma proteome, the concentration-response relationship between blood proteins and TRAP is unexplored in controlled human exposure studies. We aimed to identify concentration-dependent plasma markers of diesel exhaust (DE), a model of TRAP.

IFNγ-mediated IL-33 production is dependent on the aryl hydrocarbon receptor in human bronchial epithelial cells.

IL-33 is an alarmin produced by stromal cells and is known to promote airway inflammation. IL-33 is a critical mediator of steroid-unresponsiveness in severe asthma. We have previously shown that IFNγ, a cytokine known to be elevated in airway inflammation and severe asthma, enhances the abundance of IL-33 in bronchial epithelial cells.

A bioavailable form of curcumin suppresses cationic host defence peptides cathelicidin and calprotectin in a murine model of collagen-induced arthritis.

Curcumin, a component of the South-Asian spice turmeric, elicits anti-inflammatory functions. We have previously demonstrated that a highly bioavailable formulation of cucurmin, Cureit/Acumin™ (CUR), can suppress disease onset and severity, in a collagen-induced arthritis (CIA) mouse model. In a previous study, we have also shown that the abundance of antimicrobial host defence peptides, specifically cathelicidin (CRAMP) and calprotectin (S100A8 and S100A9), is significantly increased in the joint tissues of CIA mice.

Platelet activation and ferroptosis mediated NETosis drives heme induced pulmonary thrombosis.

Cell-free heme (CFH) is a product of hemoglobin, myoglobin and hemoprotein degradation, which is a hallmark of pathologies associated with extensive hemolysis and tissue damage. CHF and iron collectively induce cytokine storm, lung injury, respiratory distress and infection susceptibility in the lungs suggesting their key role in the progression of lung disease pathology. We have previously demonstrated that heme-mediated reactive oxygen species (ROS) induces platelet activation and ferroptosis.

Combination of IL-17A/F and TNF-α uniquely alters the bronchial epithelial cell proteome to enhance proteins that augment neutrophil migration.

Background: The heterodimer interleukin (IL)-17A/F is elevated in the lungs in chronic respiratory disease such as severe asthma, along with the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Although IL-17A/F and TNF-α are known to functionally cooperate to exacerbate airway inflammation, proteins altered by their interaction in the lungs are not fully elucidated.

Results: We used Slow Off-rate Modified Aptamer-based proteomic array to identify proteins that are uniquely and/or synergistically enhanced by concurrent stimulation with IL-17A/F and TNF-α in human bronchial epithelial cells (HBEC).

Characterization of sex-related differences in allergen house dust mite-challenged airway inflammation, in two different strains of mice.

Biological sex impacts disease prevalence, severity and response to therapy in asthma, however preclinical studies often use only one sex in murine models. Here, we detail sex-related differences in immune responses using a house dust mite (HDM)-challenge model of acute airway inflammation, in adult mice of two different strains (BALB/c and C57BL/6NJ). Female and male mice were challenged (intranasally) with HDM extract (~ 25 μg) for 2 weeks (N = 10 per group).

Sex Dimorphism of Allergen-Induced Secreted Proteins in Murine and Human Lungs.

Biological sex influences disease severity, prevalence and response to therapy in allergic asthma. However, allergen-mediated sex-specific changes in lung protein biomarkers remain undefined. Here, we report sex-related differences in specific proteins secreted in the lungs of both mice and humans, in response to inhaled allergens.

Defining the effects of traffic-related air pollution on the human plasma proteome using an aptamer proteomic array: A dose-dependent increase in atherosclerosis-related proteins.

Background: Traffic-related air pollution (TRAP) is a critical risk factor and major contributor to respiratory and cardiovascular disease (CVD). The effects of TRAP beyond the lungs can be related to changes in circulatory proteins. However, such TRAP-mediated changes have not been defined in an unbiased manner using a controlled human model.

Disrupting Tryptophan in the Central Hydrophobic Region Selectively Mitigates Immunomodulatory Activities of the Innate Defence Regulator Peptide IDR-1002.

Innate defense regulator (IDR) peptides show promise as immunomodulatory therapeutics. However, there is limited understanding of the relationship of IDR peptide sequence and/or structure with its immunomodulatory activity. We previously reported that an IDR peptide, IDR-1002, reduces airway hyperresponsiveness (AHR) and inflammation in a house dust mite (HDM)-challenged murine model of airway inflammation.

Bisphenol AF elevates procoagulant platelets by inducing necroptosis via RIPK1-inflammasome axis.

Bisphenol AF, an analogue of Bisphenol A, is an important raw material used in the production of plastic and rubber substances like plastic bottles and containers, toys, and medical supplies. Increased contamination of air, water, dust, and food with BPA/BPAF, poses an enormous threat to humans, globally. BPAF/BPA are endocrine-disrupting chemicals that mimic estrogen hormone, thus increasing the risks of various metabolic and chronic disorders.

A bioavailable form of curcumin, in combination with vitamin-D- and omega-3-enriched diet, modifies disease onset and outcomes in a murine model of collagen-induced arthritis.

Objective: Curcumin (CUR), vitamin D (D3), and omega-3-fatty acids (O3FA) individually modulate inflammation and pain in arthritis. Although these supplements are widely used, their combinatorial effects have not been defined. In this study, we examined the effects of a D3 and O3FA (VO)-enriched diet in conjunction with a highly bioavailable form of CUR (Cureit/Acumin™) in a collagen-induced arthritis (CIA) murine model.

Cathelicidin and Calprotectin Are Disparately Altered in Murine Models of Inflammatory Arthritis and Airway Inflammation.

Cationic host defense peptides (CHDP) are immunomodulatory molecules that control infections and contribute to immune homeostasis. CHDP such as cathelicidin and calprotectin expression is altered in the arthritic synovium, and in the lungs of asthma and COPD patients. Recent studies suggest a link between airway inflammation and the immunopathology of arthritis.

Characterization of immune responses and the lung transcriptome in a murine model of IL-33 challenge.

IL-33 induces airway inflammation and hyper-responsiveness in respiratory diseases. Although defined as a therapeutic target, there are limited studies that have comprehensively investigated IL-33-mediated responses in the lungs in vivo. In this study, we characterized immunological and physiological responses induced by intranasal IL-33 challenge, in a mouse model.

Bisdemethoxycurcumin promotes apoptosis in human platelets via activation of ERK signaling pathway.

Curcumin, a major bioactive component of turmeric (Curcuma longa), is known for its multiple health benefits. Curcumin as such is a mixture of its analogs: bisdemethoxycurcumin (BDMC)-3%, and demethoxycurcumin (DMC)-17%. Although the effect of curcumin on platelets is documented, the effect of BDMC and DMC on platelets is less studied.

Circulating levels of free 25(OH)D increase at the onset of rheumatoid arthritis.

Objective: Epidemiological studies suggest vitamin D deficiency as a potential risk factor for rheumatoid arthritis (RA) development, a chronic autoimmune disorder highly prevalent in indigenous North American (INA) population. We therefore profiled the circulating levels of 25-hydroxyvitaminD [25(OH)D], an active metabolite of vitamin D, in a cohort of at-risk first-degree relatives (FDR) of INA RA patients, a subset of whom subsequently developed RA (progressors).

Methods: 2007 onward, serum samples from INA RA patients and FDR were collected at the time of a structured baseline visit and stored at -20°C.

Immunomodulatory Functions of the Human Cathelicidin LL-37 (aa 13-31)-Derived Peptides are Associated with Predicted α-Helical Propensity and Hydrophobic Index.

The anti-endotoxin activity of the cationic peptide LL-37 and its derivative IG-19 is attributed to electrostatic interaction of the peptides' positive charge with negatively charged bacterial lipopolysaccharides (LPS), and in part to the alteration of intracellular mechanisms independent of peptide binding to LPS. We examined the immunomodulatory responses induced by IG-19 and four IG-19-derived scrambled peptides (IG-19a-d), in the presence and absence of LPS, in macrophages and peripheral blood-derived mononuclear cells. All peptides had identical net charge (+5) and amino acid composition, but different hydrophobicity and α-helical propensity.

Guggulipid ameliorates adjuvant-induced arthritis and liver oxidative damage by suppressing inflammatory and oxidative stress mediators.

Background: Arthritis is a common degenerative joint disease characterized by deterioration of articular cartilage, subchondral bone, and associated with immobility, pain and inflammation. The incessant action of reactive oxygen species (ROS) during progressive arthritis causes severe oxidative damage to vital organs and circulatory system.

Purpose: In this study we investigated the ability of guggulipid (GL), a lipid rich extract from the gum resin of the plant Commiphora whighitii to suppress the progressive arthritis and associated liver oxidative stress both in vivo and in vitro.

Hemin-induced platelet activation and ferroptosis is mediated through ROS-driven proteasomal activity and inflammasome activation: Protection by Melatonin.

Reactive oxygen species (ROS) are capable of inducing cell death or apoptosis. Recently, we demonstrated that lipid-ROS can mediate ferroptosis and activation of human platelets. Ferroptosis is an intracellular iron-mediated cell death, distinct from classical apoptosis and necrosis, which is mediated through the accumulation of ROS, lipid peroxides and depletion of cellular GSH.

Para-tertiary butyl catechol (PTBC), an industrial antioxidant induces human platelet apoptosis.

The catecholic derivative para-tertiary butyl catechol (PTBC) is a conventional antioxidant and polymerization inhibitor, which exhibits melanocytotoxic effects and contact dermatitis often leading to occupational leucoderma or vitiligo. Although numerous industrial workers will be in constant exposure to PTBC and its chances of getting entry into blood are most expected, its effect on blood components is still undisclosed. As platelets play a prominent role in dermatitis, inflammation, and immunity, in this study we have evaluated the effect of PTBC on human platelets in vitro.

Berberine mitigates high glucose-potentiated platelet aggregation and apoptosis by modulating aldose reductase and NADPH oxidase activity.

Diabetes mellitus (DM) is a serious metabolic disorder affecting millions of people worldwide. The high rate of mortality and morbidity during DM is attributed to the increased atherothrombotic events due to platelet activation and apoptosis leading to macro and micro vascular occlusions. The platelet hyper-reactivity and apoptosis during DM is accounted for the accumulated reactive oxygen species (ROS) due to increased aldose reductase (AR) and NADPH oxidase (NOX) activities.