Higher expression of mir-31-5p is associated with reduced risk of head and neck keloid recurrence following surgical resection.

Objective: In this study, we aimed to evaluate mir-31-5p as a prognostic biomarker of keloid disease (KD) recurrence using a retrospective, treatment naïve, surgical cohort of head and neck KD cases from Henry Ford Health.

Methods: Using a tissue microarray, mir-31-5p expression was measured with miRNAscope, and mir-31-5p cell positivity was determined with QuPath. Logistic regression was used to test the association between mir-31-5p positive cells and KD recurrence at 1 year.

Dissociation of Hypertension and Renal Damage After Cessation of High-Salt Diet in Dahl Rats.

Background: Every year, thousands of patients with hypertension reduce salt consumption in an effort to control their blood pressure. However, hypertension has a self-sustaining character in a significant part of the population. We hypothesized that chronic hypertension leads to irreversible renal damage that remains after removing the trigger, causing an elevation of the initial blood pressure.

Inflammatory endotype of odontogenic sinusitis.

Background: Odontogenic sinusitis (ODS) is distinct from non-odontogenic rhinosinusitis with regard to clinical features as well as diagnostic and therapeutic approaches. While numerous studies have explored immune profiles of chronic rhinosinusitis, very few studies have explored the inflammatory endotype of ODS.

Methods: Odontogenic sinusitis was diagnosed by confirming infectious sinusitis adjacent to infectious maxillary odontogenic pathology.

Racial differences in the systemic inflammatory response to prostate cancer.

Systemic inflammation may increase risk for prostate cancer progression, but the role it plays in prostate cancer susceptibility is unknown. From a cohort of over 10,000 men who had either a prostate biopsy or transurethral resection that yielded a benign finding, we analyzed 517 incident prostate cancer cases identified during follow-up and 373 controls with one or more white blood cell tests during a follow-up period between one and 18 years. Multilevel, multivariable longitudinal models were fit to two measures of systemic inflammation, neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR), to determine NLR and MLR trajectories associated with increased risk for prostate cancer.

Growth and differentiation factor 15 and NF-κB expression in benign prostatic biopsies and risk of subsequent prostate cancer detection.

Growth and differentiation factor 15 (GDF-15), also known as macrophage inhibitory cytokine 1 (MIC-1), may act as both a tumor suppressor and promotor and, by regulating NF-κB and macrophage signaling, promote early prostate carcinogenesis. To determine whether expression of these two inflammation-related proteins affect prostate cancer susceptibility, dual immunostaining of benign prostate biopsies for GDF-15 and NF-κB was done in a study of 503 case-control pairs matched on date, age, and race, nested within a historical cohort of 10,478 men. GDF-15 and NF-κB expression levels were positively correlated (r = 0.

Asthma and its relationship to mitochondrial copy number: Results from the Asthma Translational Genomics Collaborative (ATGC) of the Trans-Omics for Precision Medicine (TOPMed) program.

Background: Mitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis.

Objective: Given the heightened level of cellular activity in patients with asthma, we sought to determine whether mitochondrial DNA (mtDNA) copy number measured in peripheral blood differed between individuals with and without asthma.

Methods: Whole genome sequence data was generated as part of the Trans-Omics for Precision Medicine (TOPMed) Program on participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) and the Study of African Americans, Asthma, Genes, & Environment II (SAGE II).

The interplay of growth differentiation factor 15 (GDF15) expression and M2 macrophages during prostate carcinogenesis.

M2 (tumor-supportive) macrophages may upregulate growth differentiation factor 15 (GDF15), which is highly expressed in prostate tumors, but the combined utility of these markers as prognostic biomarkers are unclear. We retrospectively studied 90 prostate cancer cases that underwent radical prostatectomy as their primary treatment and were followed for biochemical recurrence (BCR). These cases also had a benign prostate biopsy at least 1 year or more before their prostate cancer surgery.

F-Actin is associated with a worsening qSOFA score and intensive care unit admission in emergency department patients at risk for sepsis.

We previously demonstrated that plasma levels of F-actin and Thymosin Beta 4 differs among patients with septic shock, non-infectious systemic inflammatory syndrome and healthy controls and may serve as biomarkers for the diagnosis of sepsis. The current study aims to determine if these proteins are associated with or predictive of illness severity in patients at risk for sepsis in the Emergency Department (ED). Prospective, biomarker study enrolling patients (>18 years) who met the Shock Precautions on Triage Sepsis rule placing them at-risk for sepsis.

Potential effect of anti-inflammatory drug use on PSA kinetics and subsequent prostate cancer diagnosis: Risk stratification in black and white men with benign prostate biopsy.

Background: Rising prostate-specific antigen (PSA) levels are associated with both increased risk of prostate cancer and prostatic inflammation. The confounding effects of inflammation on the utility of PSA kinetics to predict prostate cancer may be partially mitigated by anti-inflammatory drug use. We investigated the influence of anti-inflammatory drug use on the association of PSA kinetics with prostate cancer risk.

Breast Milk Transforming Growth Factor β Is Associated With Neonatal Gut Microbial Composition.

Background And Objectives: Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. Although breast-feeding is known to affect neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated 3 essential breast milk cytokines and their association with early life gut microbiota.

Plasma levels of F-actin and F:G-actin ratio as potential new biomarkers in patients with septic shock.

Objective: To compare plasma levels of F-actin, G-actin and thymosin beta 4 (TB4) in humans with septic shock, noninfectious systemic inflammatory response syndrome (SIRS) and healthy controls.

Results: F-actin was significantly elevated in septic shock as compared with noninfectious SIRS and healthy controls. G-actin levels were greatest in the noninfectious SIRS group but significantly elevated in septic shock as compared with healthy controls.

Early pregnancy vitamin D and patterns of antenatal inflammation in African-American women.

Vitamin D is essential for the health of both mother and fetus during pregnancy. In the nonpregnant state, vitamin D demonstrates anti-inflammatory effects, but little is known about this relationship during pregnancy. African-American women are at a higher risk of vitamin D deficiency and for altered inflammatory responses during pregnancy.

Differentiating asthma phenotypes in young adults through polyclonal cytokine profiles.

Background: Recent research has emphasized the need to better discriminate asthma phenotypes and consider underlying mechanistic endotypes in epidemiologic and clinical studies. Although allergic asthma and nonallergic asthma are frequently combined into 1 disease category in observational research and clinical trials, few studies have investigated the extent to which these 2 separate phenotypes are associated with distinct cytokine immunologic profiles in a representative young adult population.

Objective: To investigate the cytokine production-based endotypes underlying the clinical phenotypes of allergic and nonallergic asthma in a population-based birth cohort evaluated as young adults.

Transforming growth factor beta (TGFβ1) in breast milk and indicators of infant atopy in a birth cohort.

Background: The infant gut's ability to suppress immunologic reactions to food proteins could be influenced by levels of TGFβ in breast milk. We hypothesized that lower levels of TGFβ(1) in the breast milk (BM) of mothers in the WHEALS birth cohort are associated with atopy at infant age 2-3 yrs.

Methods: We used data collected during infancy in addition to the results of skin prick tests (SPT+) and measures of specific IgE >0.

Mesenchymal stem cells deliver synthetic microRNA mimics to glioma cells and glioma stem cells and inhibit their cell migration and self-renewal.

MicroRNAs (miRNAs) have emerged as potential cancer therapeutics; however, their clinical use is hindered by lack of effective delivery mechanisms to tumor sites. Mesenchymal stem cells (MSCs) have been shown to migrate to experimental glioma and to exert anti-tumor effects by delivering cytotoxic compounds. Here, we examined the ability of MSCs derived from bone marrow, adipose tissue, placenta and umbilical cord to deliver synthetic miRNA mimics to glioma cells and glioma stem cells (GSCs).

Treatment with N-acetyl-seryl-aspartyl-lysyl-proline prevents experimental autoimmune myocarditis in rats.

Myocarditis is commonly associated with cardiotropic infections and has been linked to development of autoimmunity. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a naturally occurring tetrapeptide that prevents inflammation and fibrosis in hypertension and other cardiovascular diseases; however, its effect on autoimmune-mediated cardiac diseases remains unknown. We studied the effects of Ac-SDKP in experimental autoimmune myocarditis (EAM), a model of T cell-mediated autoimmune disease.

The entirely carbohydrate immunogen Tn-PS A1 induces a cancer cell selective immune response and cytokine IL-17.

The tumor-associated carbohydrate antigen/hapten Thomsen-nouveau (Tn; a-D-GalpNAc-ONH2) was conjugated to a zwitterionic capsular polysaccharide, PS A1, from commensal anaerobe Bacteroides fragilis ATCC 25285/NCTC 9343 for the development of an entirely carbohydrate cancer vaccine construct and probed for immunogenicity. This communication discloses that murine anti-Tn IgG3 antibodies both bind to and recognize human tumor cells that display the Tn hapten. Furthermore, the sera from immunization of mice with Tn-PS A1 contain cytokine interleukin 17 (IL-17A), which is known to possess anti-tumor function and represents a striking difference to an IL-2, and IL-6 profile obtained with anti-PS A1 sera.

Synthesis and Biological Evaluation of Novel -phenyl-5-carboxamidyl Isoxazoles as Potential Chemotherapeutic Agents for Colon Cancer.

A new series of isoxazole derivatives, -phenyl-5-carboxamidyl isoxazoles, was investigated for their anticancer activity with solid tumor selectivity. Six -phenyl-5-carboxamidylisoxazoles were chemically synthesized and evaluated by the disk-diffusion assay and IC cytotoxicity determination. The results showed that one of the derivatives, compound -(4-chlorophenyl)-5-carboxamidyl isoxazole, was the most active against colon 38 and CT-26 mouse colon tumor cells with an IC of 2.

Regulatory T cells vary over bleeding segments in asthmatic and non-asthmatic women.

Sex hormones may play an important role in observed gender differences in asthma incidence and severity. Regulatory T cells (Treg cells) are presumed to be involved in asthma and may vary with hormone levels. To investigate the effects of sex hormones on levels of Treg cells (percentage of CD4+CD25+Foxp3+ lymphocytes that are CD127-), a cohort of 13 women (6 with and 7 without an asthma diagnosis) had blood drawn multiple times over the course of a bleeding segment (bleeding interval plus the following bleeding-free interval) and collected urine samples daily for measurement of estrogen (estrone E1C) and progesterone (pregnanediol-glucuronide PDG) metabolites.

Within-woman change in regulatory T cells from pregnancy to the postpartum period.

Regulatory T cells (Treg cells) are an important area of investigation in human health and disease. In this study, the trajectory of percentage of Treg cells (defined as CD4+CD25+Foxp3+CD127--lymphocytes) was measured in the blood of 208 women during pregnancy and up to three additional times in the postpartum period (1, 6 and 12 months postpartum). Whether the trajectory was affected by gravidity, parity, neonatal sex, pet exposure, maternal atopic and asthma status, smoking, maternal race or other pregnancy factors was examined.

Man's best friend? The effect of pet ownership on house dust microbial communities.

Pet-ownership, which has been shown to be protective against allergic disease development, is associated with increased house dust bacterial diversity and fewer fungal species, suggesting a potentially microbial-based mechanism for this protective effect.

Regulatory T cells in prenatal blood samples: variability with pet exposure and sensitization.

Fetal exposures have come under investigation as risk factors of early life allergic disease. In this study we aimed to examine the relationships between dog or cat exposure and naturally occurring regulatory T cells (Treg cells), thought to play an important role in immune tolerance, in pregnant women. A cross-sectional analysis was conducted among 204 pregnant women who were queried regarding dog and cat exposure.

Gene-environment interactions between CD14 C-260T and endotoxin exposure on Foxp3+ and Foxp3- CD4+ lymphocyte numbers and total serum IgE levels in early childhood.

Background: Innate immune system stimuli, such as endotoxin, seem to affect allergy risk. Previously, we described gene-environment interactions between the endotoxin receptor polymorphism C-260T of the CD14 gene and endotoxin exposure on total serum IgE level; however, the mechanism of this interaction is not known.

Objective: To examine whether this gene-environment interaction affects early CD4(+)Foxp3(-) or CD4(+)Foxp3(+) lymphocyte numbers.

SDF-1 and CXCR4 are up-regulated by VEGF and contribute to glioma cell invasion.

Glioma cells produce vascular endothelial growth factor (VEGF) to induce vascularization and thereby supply the malignant tissue with oxygen and nutrients. However, little is known about the direct effects of VEGF on tumor cells. In this study, we investigate the ability of VEGF to promote proliferation and invasion of human glioma cells (U251n).