Biodistribution Analysis of Peptide-Coated Magnetic Iron Nanoparticles: A Simple and Quantitative Method.

Biodistribution tracks compounds or molecules of interest in vivo to understand a compound's anticipated efficacy and safety. Nanoparticles deliver nucleic acid and drug payloads and enhance tumor permeability due to multiple properties such as high surface area to volume ratio, surface functionalization, and modifications. Studying the in vivo biodistribution of nanoparticles documents the effectiveness and safety of nanoparticles and facilitates a more application-driven approach for nanoparticle development that allows for more successful translation into clinical use.

Biodistribution Analysis of Peptide-Coated Magnetic Iron Nanoparticles: A Simple and Quantitative Method.

Biodistribution is the tracking of compounds or molecules of interest in the subject which is integral to understanding their anticipated efficacy and safety. Nanoparticles are highly desirable delivery systems which have the ability to deliver higher nucleic acid and drug payloads and they have enhanced tumor permeability due to their unique properties such as high surface area to volume ratio. Studying the biodistribution of nanoparticles is crucial to understand their effectiveness and safety in vivo, facilitate a more application driven approach for nanoparticle development which will lead to their successful translation into clinical use.

Tick Intrastadial Feeding and Its Role on IgE Production in the Murine Model of Alpha-gal Syndrome: The Tick "Transmission" Hypothesis.

Recent studies have provided strong evidence indicating that lone star tick bites are a cause of AGS (alpha-gal syndrome, also known as red meat allergy RMA) in humans. AGS is characterized by an increase in IgE antibody production against galactose-alpha-1,3-galactose (aGal), which is a common glycan found in mammalian tissue, except in Old World monkeys and humans. The main causative factor of AGS, the lone star tick (), is broadly distributed throughout the east and midwest of the United States and is a vector of a wide range of human and animal pathogens.

Complement Initiation Varies by Sex in Intestinal Ischemia Reperfusion Injury.

Intestinal ischemia reperfusion (IR)-induced tissue injury represents an acute inflammatory response with significant morbidity and mortality. The mechanism of IR-induced injury is not fully elucidated, but recent studies suggest a critical role for complement activation and for differences between sexes. To test the hypothesis that complement initiation differs by sex in intestinal IR, we performed intestinal IR on male and female WT C57B6L/, C1q, MBL, or properdin (P) mice.

Eicosanoid production varies by sex in mesenteric ischemia reperfusion injury.

Intestinal ischemia/reperfusion (I/R)-induced injury is an inflammatory response with significant morbidity and mortality. The early inflammatory response includes neutrophil infiltration. However, the majority of rodent studies utilize male mice despite a sexual dimorphism in intestinal I/R-related diseases.

Beta2 glycoprotein I-derived therapeutic peptides induce sFlt-1 secretion to reduce melanoma vascularity and growth.

Melanoma, a form of skin cancer, is one of the most common cancers in young men and women. Tumors require angiogenesis to provide oxygen and nutrients for growth. Pro-angiogenic molecules such as VEGF and anti-angiogenic molecules such as sFlt-1 control angiogenesis.

Essential Role of Complement in Pregnancy: From Implantation to Parturition and Beyond.

The complement cascade was identified over 100 years ago, yet investigation of its role in pregnancy remains an area of intense research. Complement inhibitors at the maternal-fetal interface prevent inappropriate complement activation to protect the fetus. However, this versatile proteolytic cascade also favorably influences numerous stages of pregnancy, including implantation, fetal development, and labor.

A Study of the Cellular Uptake of Magnetic Branched Amphiphilic Peptide Capsules.

Understanding cellular uptake mechanisms of nanoparticles with therapeutic potential has become critical in the field of drug delivery. Elucidation of cellular entry routes can aid in the dissection of the complex intracellular trafficking and potentially allow for the manipulation of nanoparticle fate after cellular delivery (i.e.

Drivers and regulators of humoral innate immune responses to infection and cancer.

The complement cascade consists of cell bound and serum proteins acting together to protect the host from pathogens, remove cancerous cells and effectively links innate and adaptive immune responses. Despite its usefulness in microbial neutralization and clearance of cancerous cells, excessive complement activation causes an immune imbalance and tissue damage in the host. Hence, a series of complement regulatory proteins present at a higher concentration in blood plasma and on cell surfaces tightly regulate the cascade.

Interactions of viruses and the humoral innate immune response.

The innate immune response is crucial for defense against virus infections where the complement system, coagulation cascade and natural antibodies play key roles. These immune components are interconnected in an intricate network and are tightly regulated to maintain homeostasis and avoid uncontrolled immune responses. Many viruses in turn have evolved to modulate these interactions through various strategies to evade innate immune activation.

Role of B1 and B2 lymphocytes in placental ischemia-induced hypertension.

Preeclampsia is a prevalent pregnancy complication characterized by new-onset maternal hypertension and inflammation, with placental ischemia as the initiating event. Studies of others have provided evidence for the importance of lymphocytes in placental ischemia-induced hypertension; however, the contributions of B1 versus B2 lymphocytes are unknown. We hypothesized that peritoneal B1 lymphocytes are important for placental ischemia-induced hypertension.

Interactions between the complement and endothelin systems in normal pregnancy and following placental ischemia.

Preeclampsia is characterized by new onset hypertension and fetal growth restriction and is associated with aberrant activation of the innate immune complement system and stressed or ischemic placenta. Previous studies have suggested a role for both endothelin and complement system activation products in new onset hypertension in pregnancy, but inter-relationships of the pathways are unclear. We hypothesized that complement activation following placental ischemia stimulates the endothelin pathway to cause hypertension and impair fetal growth.

Transforming Growth Factor Beta Signaling in Dendritic Cells Is Required for Immunotolerance to Sperm in the Epididymis.

The epididymis exhibits a less restrictive physical blood-tissue barrier than the testis and, while numerous immunosuppressive factors have been identified in the latter, no mechanisms for epididymal immunotolerance have been identified to date. Therefore, data are currently insufficient to explain how the immune system tolerates the extremely large load of novel antigens expressed on sperm, which become present in the male body after puberty, i.e.

The Complement System and Preeclampsia.

Purpose Of Review: Preeclampsia affects 3-4% of pregnancies with few treatment options to reduce maternal and fetal harm. Recent evidence that targeting the complement system may be an effective therapeutic strategy in prevention or treatment of preeclampsia will be reviewed.

Recent Findings: Studies in humans confirm the safety and efficacy of C5 blockade in complement-mediated disorders of pregnancy, including preeclampsia.

Role of IgM and angiotensin II Type I receptor autoantibodies in local complement activation in placental ischemia-induced hypertension in the rat.

Preeclampsia is characterized by development of hypertension during pregnancy and reduced placental perfusion. Previous studies in a rat model of placental ischemia-induced hypertension demonstrated that inhibiting complement activation attenuated increased maternal blood pressure with C3a and C5a identified as the important products of complement activation. Given that in other forms of ischemia both natural IgM and antigen antibody complexes initiate complement activation, we hypothesized that placental ischemia exposes neoepitopes recognized by IgM to cause local complement activation and hypertension.

Overexpression of eIF5 or its protein mimic 5MP perturbs eIF2 function and induces ATF4 translation through delayed re-initiation.

ATF4 is a pro-oncogenic transcription factor whose translation is activated by eIF2 phosphorylation through delayed re-initiation involving two uORFs in the mRNA leader. However, in yeast, the effect of eIF2 phosphorylation can be mimicked by eIF5 overexpression, which turns eIF5 into translational inhibitor, thereby promoting translation of GCN4, the yeast ATF4 equivalent. Furthermore, regulatory protein termed eIF5-mimic protein (5MP) can bind eIF2 and inhibit general translation.

TLR2 Regulates Complement-Mediated Inflammation Induced by Blood Loss During Hemorrhage.

Hemorrhagic shock resulting from blood loss directs the majority of the blood to the vital organs, dramatically reducing blood flow to the intestines and resulting in damage and inflammation. The excessive intestinal inflammatory response includes pro-inflammatory cytokines and complement activation, although the mechanism is not clear. Toll-like receptors play a vital role in the innate immune response and toll-like receptor 2 (TLR2) is required for intestinal ischemia/reperfusion-induced injury.

Phospholipid scramblase 1 is required for β2-glycoprotein I binding in hypoxia and reoxygenation-induced endothelial inflammation.

Multiple pathologic conditions, including hemorrhage, tumor angiogenesis, and ischemia-reperfusion events, will result in hypoxia and subsequent reperfusion. Previous studies have analyzed the lipid changes within whole tissues and indicated that ischemia-reperfusion altered tissue and cellular phospholipids. Using an in vitro cell culture model of hypoxia and reoxygenation, we examined the endothelial lipid changes.

Evasion and interactions of the humoral innate immune response in pathogen invasion, autoimmune disease, and cancer.

The humoral innate immune system is composed of three major branches, complement, coagulation, and natural antibodies. To persist in the host, pathogens, such as bacteria, viruses, and cancers must evade parts of the innate humoral immune system. Disruptions in the humoral innate immune system also play a role in the development of autoimmune diseases.

TLR2 modulates antibodies required for intestinal ischemia/reperfusion-induced damage and inflammation.

In multiple clinical conditions, including trauma and hemorrhage, reperfusion magnifies ischemic tissue damage. Ischemia induces expression of multiple neoantigens, including lipid alterations that are recognized by the serum protein, β2-glycoprotein I (β2-GPI). During reperfusion, binding of β2-GPI by naturally occurring Abs results in an excessive inflammatory response that may lead to death.

Membrane lipid interactions in intestinal ischemia/reperfusion-induced Injury.

Ischemia, lack of blood flow, and reperfusion, return of blood flow, are a common phenomenon affecting millions of Americans each year. Roughly 30,000 Americans per year experience intestinal ischemia-reperfusion (IR), which is associated with a high mortality rate. Previous studies of the intestine established a role for neutrophils, eicosanoids, the complement system and naturally occurring antibodies in IR-induced pathology.