Vanillic Acid Improves Stress Resistance and Substantially Extends Life Span in Caenorhabditis elegans.

Aging is the root cause of several pathologies like neurological and cardiovascular diseases. Identifying compounds that improve health span and extend life span, called geroprotectors, could be crucial to preventing or at least delaying the onset of age-related diseases. In this regard, the nematode Caenorhabditis elegans (C. elegans) is emerging as an easy, efficient, low-cost model system to screen natural products and identify novel geroprotectors. Phenolic acids can be found in a wide range of natural products that are part of the human diet. Vanillic acid (VA) is a phenolic acid that has previously been attributed with antioxidant, anti-inflammatory, and neuroprotective features. To determine whether these beneficial health effects amount to an extension of health span and life span, in this work, we thoroughly explore the effect of VA on C. elegans stress resistance and life span. We found that VA increases thermotolerance (19.4%), reduces protein aggregation (between 30% and 40%), improves motility, and extends life span by almost 50%, an extent hardly ever achieved with a natural compound. The increased thermotolerance induced by VA is independent of the insulin/insulin-like growth factor-1 signaling pathway but requires heat shock factor-1 and is associated with increased heat shock protein-4 (HSP-4) and hsp-16.2 expression. These results provide new insight into understanding the therapeutical properties of VA and warrant further investigation of VA as a novel geroprotector.

Human platelets and megakaryocytes express defensin alpha 1.

Platelets are anucleate cells that have a role in several innate immune functions, including the secretion of proteins with antimicrobial activity. Several studies have demonstrated the ability of platelets to secrete thrombin-induced platelet microbicidal proteins and antimicrobial peptides, like hBD-1. However, the expression and secretion of defensins of the alpha family by platelets have not been fully elucidated. The aim of this study was to characterize the expression of defensin alpha 1 (DEFA1) in human platelets and megakaryocytes. Our data indicate that DEFA1 mRNA and protein are present in peripheral blood platelets and in the megakaryoblastic leukemia cell line (MEG-01). DEFA1 co-localize with α-granules of platelets and MEG-01 cells, and was also detected in cytoplasm of MEG-01 cells. The assay of our in vitro model of platelet-like particles (PLPs) revealed that MEG-01 cells could transfer DEFA1 mRNA to their differentiated PLPs. Furthermore, platelets secreted DEFA1 into the culture medium when activated with thrombin, adenosine diphosphate, and lipopolysaccharide; meanwhile, MEG-01 cells secreted DEFA1 when activated with thrombopoietin. Platelet's secreted DEFA1 can rebind to platelet's surface and have antibacterial activity against the gram-negative bacteria Escherichia coli. In summary, our data indicate that both, human platelets and megakaryocytes, can express and secrete DEFA1. These results suggest a new role of platelets and megakaryocytes in the innate immune response.

Modification of immunological features in human platelets during sepsis.

Sepsis is an organic dysfunction that puts at risk the life of patients suffering this disorder due to an exacerbated immunological response to the infection mediated by the host. Platelets have been largely researched on sepsis owing to its role in Disseminated Intracellular Coagulation (DIC) and because thrombocytopenia is an important clinical feature of these patients. Nevertheless, a great number of evidence shows that platelets have also an important role in immunological response since they have pattern recognition receptors, chemokine receptors and granules with stored soluble mediators. In this work, the immunological features of platelets in individuals with sepsis are described. The results show that platelets of these individuals have high levels of surfaces expression of TLR4, CD62P, CD32 and thrombin receptor 1 (PAR-1), these platelets have also greater capability to join Escherichia coli, and show a different profile of soluble mediators (IL-1ß, CD40L and TNF-α). Platelets from patients with sepsis form aggregates with neutrophils in circulation, but are unable to induce the production of reactive oxygen species. This research describes important features of platelets to help the understanding of the immunological role of these cells in sepsis.

Irregular antibodies in no hemolytic autoimmune diseases are able to induce erythrophagocytosis.

Irregular antibodies are produced by alloimmunization because of pregnancies or blood transfusions. They are called "irregular" due to target erythrocyte antigens from "rare blood systems," those different from the ABO system. Irregular antibodies have been widely investigated in immunohematology since their presence in blood donors may lead to difficulties in blood typing and in blood cross-matching, or to induce hemolytic transfusion reactions. Nevertheless, their incidence and participation in the physiopathology of autoimmune diseases have not been thoroughly studied. In this work, we analyzed the presence and pro-hemolytic capabilities of irregular antibodies in patients with different autoimmune diseases lacking signs of hemolytic anemia, in comparison with healthy multiparous women. Five of 141 autoimmune patients (3.5 %) and two of 77 multiparous women (2.6 %) were positive. Although frequency was relatively low and similar in both populations, the targeted antigens were Kell (k, Kpb, Jsb) and Luth (Lub) in multiparous women, and the same plus Duffy (Fya), Kidd (Jka) and MNS (M, s) in autoimmune patients. Irregular antibodies from autoimmune patients did not induce complement-mediated hemolysis (intravascular), but they were able to induce macrophages-mediated phagocytosis (extravascular hemolysis) in vitro. It is the first approach exploring the presence of irregular antibodies associated with the loss of immune tolerance and demonstrating their hemolytic potential in autoimmune patients without hemolytic manifestations. The presence of irregular antibodies targeted to Duffy (Fya), Kidd (Jka) and MNS (M, s) antigens only in autoimmune patients suggests a loss of immune tolerance to these erythrocyte antigens.