Stability Characterization of the Novel Anti-Cancer HM-10/10 HDL-Mimetic Peptide.

Epithelial adenocarcinoma of the ovary and colon are associated with the highest rates of cancer-related deaths in women in the U.S. The literature supports the role of HDL-associated apolipoproteins in the treatment of cancer and other pro-inflammatory diseases. Previously, we developed a novel 20-amino acid mimetic peptide, HM-10/10, which potently inhibits tumor development and growth in colon and ovarian cancer. Here, we report the properties of HM-10/10 relative to its stability in vitro. The results demonstrated that HM-10/10 had the highest half-life in human plasma compared to plasma from other species tested. HM-10/10 demonstrated stability in human plasma and simulated gastric environment, increasing its promise as an oral pharmaceutical. However, under conditions modeling the small intestine, HM-10/10 demonstrated significant degradation, likely due to the peptidases encountered therein. Furthermore, HM-10/10 demonstrated no evidence of time-dependent drug-drug interactions, although it demonstrated CYP450 induction slightly above cutoff. As proteolytic degradation is a common limitation of peptide-based therapeutics, we are pursuing strategies to improve the stability properties of HM-10/10 by extending its bioavailability while retaining its low toxicity profile. HM-10/10 holds promise as a new agent to address the international women's health crisis of epithelial carcinomas of the ovary and colon.

Understanding Health Disparities in Preeclampsia: A Literature Review.

Preeclampsia is a multifactorial pathology with negative outcomes in affected patients in both the peripartum and postpartum period. Black patients in the United States, when compared to their White and Hispanic counterparts, have higher rates of preeclampsia. This article aims to review the current literature to investigate how race, social determinants of health, and genetic profiles influence the prevalence and outcomes of patients with preeclampsia. Published studies utilized in this review were identified through PubMed using authors' topic knowledge and a focused search through a Medline search strategy. These articles were thoroughly reviewed to explore the contributing biosocial factors, genes/biomarkers, as well as negative outcomes associated with disparate rates of preeclampsia. Increased rates of contributing comorbidities, including hypertension and obesity, which are largely associated with low access to care in Black patient populations lead to disparate rates of preeclampsia in this population. Limited research shows an association between increased rate of preeclampsia in Black patients and specific APOL1, HLA-G, and PP13 gene polymorphisms as well as factor V Leiden mutations. Further research is required to understand the use of certain biomarkers in predicting preeclampsia within racial populations. Understanding contributing biosocial factors and identifying genes that may predispose high-risk populations may help to address the disparate rates of preeclampsia in Black patients as described in this review. Further research is required to understand if serum, placental, or urine biomarkers may be used to predict individuals at risk of developing preeclampsia in pregnancy. KEY POINTS: · Prevalence of preeclampsia in the U.S. is higher in Black patients compared to other racial groups.. · Patients with preeclampsia are at risk for poorer health outcomes both during and after delivery.. · Limited research suggests specific biomarkers or gene polymorphisms contribute to this difference; however, explanations for this disparity are multifactorial and further investigation is necessary..

Metabolites Involved in Immune Evasion by Batrachochytrium dendrobatidis Include the Polyamine Spermidine.

Amphibians have been declining around the world for more than four decades. One recognized driver of these declines is the chytrid fungus Batrachochytrium dendrobatidis, which causes the disease chytridiomycosis. Amphibians have complex and varied immune defenses against B. dendrobatidis, but the fungus also has a number of counterdefenses. Previously, we identified two small molecules produced by the fungus that inhibit frog lymphocyte proliferation, methylthioadenosine (MTA) and kynurenine (KYN). Here, we report on the isolation and identification of the polyamine spermidine (SPD) as another significant immunomodulatory molecule produced by B. dendrobatidis SPD and its precursor, putrescine (PUT), are the major polyamines detected, and SPD is required for growth. The major pathway of biosynthesis is from ornithine through putrescine to spermidine. An alternative pathway from arginine to agmatine to putrescine appears to be absent. SPD is inhibitory at concentrations of ≥10 µM and is found at concentrations between 1 and 10 µM in active fungal supernatants. Although PUT is detected in the fungal supernatants, it is not inhibitory to lymphocytes even at concentrations as high as 100 µM. Two other related polyamines, norspermidine (NSP) and spermine (SPM), also inhibit amphibian lymphocyte proliferation, but a third polyamine, cadaverine (CAD), does not. A suboptimal (noninhibitory) concentration of MTA (10 µM), a by-product of spermidine synthesis, enhances the inhibition of SPD at 1 and 10 µM. We interpret these results to suggest that B. dendrobatidis produces an "armamentarium" of small molecules that, alone or in concert, may help it to evade clearance by the amphibian immune system.

An analysis of the relationships between peer support and diabetes outcomes in adolescents with type 1 diabetes.

This study explores the relationships between the various subtypes of global and diabetes-specific peer support and health outcomes in adolescents with type 1 diabetes. Global peer support significantly predicted self-care and glycated haemoglobin, although no associations were identified for diabetes-specific support overall, nor its factors. When comparing participants with above or below average glycaemic control, significantly greater diabetes-specific support was reported in those with poorer control. It is suggested that this may be related to feelings of nagging, in which diabetes-specific support is perceived as harassment.