Glucocorticoid-Induced Leucine Zipper (GILZ) in Cardiovascular Health and Disease

Glucocorticoids (GCs) are essential in regulating functions and homeostasis in many biological systems and are extensively used to treat a variety of conditions associated with immune/inflammatory processes. GCs are among the most powerful drugs for the treatment of autoimmune and inflammatory diseases, but their long-term usage is limited by severe adverse effects. For this reason, to envision new therapies devoid of typical GC side effects, research has focused on expanding the knowledge of cellular and molecular effects of GCs. GC-induced leucine zipper (GILZ) is a GC-target protein shown to mediate several actions of GCs, including inhibition of the NF-κB and MAPK pathways. GILZ expression is not restricted to immune cells, and it has been shown to play a regulatory role in many organs and tissues, including the cardiovascular system. Research on the role of GILZ on endothelial cells has demonstrated its ability to modulate the inflammatory cascade, resulting in a downregulation of cytokines, chemokines, and cellular adhesion molecules. GILZ also has the capacity to protect myocardial cells, as its deletion makes the heart, after a deleterious stimulus, more susceptible to apoptosis, immune cell infiltration, hypertrophy, and impaired function. Despite these advances, we have only just begun to appreciate the relevance of GILZ in cardiovascular homeostasis and dysfunction. This review summarizes the current understanding of the role of GILZ in modulating biological processes relevant to cardiovascular biology.

Regulation of CEACAM Family Members by IBD-Associated Triggers in Intestinal Epithelial Cells, Their Correlation to Inflammation and Relevance to IBD Pathogenesis

Carcinoembryogenic antigen cellular adhesion molecules (CEACAMs) are intercellular adhesion molecules highly expressed in intestinal epithelial cells. CEACAM1, -3, -5, -6, -7 are altered in patients suffering from colon cancer and inflammatory bowel diseases (IBD), but their role in the onset and pathogenesis of IBD is not well known. Herein, we aim to correlate CEACAM1, -3, -5, -6, -7 expression to the degree of inflammation in pediatric and adult IBD colon biopsies and to examine the regulation of CEACAMs on human intestinal epithelial cell lines (C2BBe1/HT29) by different IBD-associated triggers (cytokines, bacteria/metabolites, emulsifiers) and IBD-drugs (6-Mercaptopurine, Prednisolone, Tofacitinib). Biopsies from patients with pediatric Crohn’s disease (CD) and adult ulcerative colitis (UC, active/inactive disease) showed a significant increase in CEACAM3, -5, -6 expression, while CEACAM5 expression was reduced in adult CD patients (active/inactive disease). Intestinal epithelial cells cultured with a pro-inflammatory cytokine cocktail and Adherent-invasive Escherichia coli (AIEC) showed a rapid induction of CEACAM1, -5, -7 followed by a reduced RNA and protein expression overtime and a constant expression of CEACAM3, correlating with IL-8 expression. Cells cultured with the emulsifier polysorbate-80 resulted in a significant induction of CEACAM3, -5, -6, -7 at a late time point, while SCFA treatment reduced CEACAM1, -5, -7 expression. No major alterations in expression of CEACAMs were noted on cells cultured with the commensal Escherichia coli K12 or the pathogen Salmonella typhimurium. IBD drugs, particularly Tofacitinib, significantly reduced cytokine-induced CEACAM1, -3, -5, -6, -7 expression associated with a reduced IL-8 secretion. In conclusion, we provide new evidence on the regulation of CEACAMs by different IBD-associated triggers, identifying a role of CEACAMs in IBD pathogenesis.

Platelet-rich plasma in interventional dermatology and trichology: How far have we come?

Platelet-rich plasma (PRP) contains several growth factors and cellular adhesion molecules which promote wound healing, angiogenesis and accelerate the rejuvenation of skin and hair follicles. With its proven regenerative and regrowth potential in a plethora of conditions, PRP has been deemed as the “futuristic elixir.” Current evidence suggests that PRP effectively stimulates angiogenesis, collagen as well as elastin regeneration, and is a safe, easy to prepare, minimally invasive technique with limited downtime, and negligible risk of allergic/hypersensitivity reactions owing to its autologous nature. It has shown excellent results when utilized as monotherapy or in combination with microneedling or ablative lasers in acne scars, post-burn or post-traumatic scars, melasma, striae distensae, chronic ulcers, and lichen sclerosus. PRP injections or PRP combined with microneedling are increasingly being utilized for skin rejuvenation and recently have been utilized to provide non-invasive face lifts. A novel technique combining non-cultured epidermal cell suspension suspended in PRP results in superior repigmentation outcomes in case of vitiligo. Use of PRP alone or in combination with hair transplant in androgenetic alopecia is another well-researched indication and its use has been successfully extrapolated to indications such as alopecia areata, chronic telogen effluvium, and cicatricial alopecia. In spite of its established efficacy in such a vast number of indications, PRP should be used with utmost caution. These growth mediators exert their own endocrine, paracrine, and enzymatic effects, the complete influence of which still remains a mystery and only years of experience, in the times to come will unravel the absolute power of our “mighty dragon warrior.”

Long-term physical training in adolescent sprint and middle distance swimmers alters the composition of circulating T and NK cells which correlates with soluble ICAM-1 serum concentrations

Purpose It remains unknown how different training intensities and volumes chronically impact circulating lymphocytes and cellular adhesion molecules. First, we aimed to monitor changes in NK and T cells over a training season and relate these to training load. Second, we analyzed effects of training differences between swimmers on these cells. Finally, we examined if changes in lymphocytes were associated with sICAM-1 concentrations. Methods We analyzed weekly training volume, training intensity, proportions of T and NK cells and serum sICAM-1 in eight sprint (SS) and seven middle-distance swimmers (MID) at three points over a 16-week training period: at the start (t0), after 7 weeks of increased training load (t7) and after 16 weeks, including 5-day taper (t16). Results Training volume of all swimmers was statistically higher and training intensity lower from t0–t7 compared to t7–t16 (p = 0.001). Secondly, training intensity was statistically higher in SS from t0–t7 (p = 0.004) and t7–t16 (p = 0.015), while MID had a statistically higher training volume from t7–t16 (p = 0.04). From t0–t7, NK (p = 0.06) and CD45RA+CD45RO+CD4+ cells (p < 0.001) statistically decreased, while CD45RA−CD45RO+CD4+ cells (p = 0.024) statistically increased. In a subgroup analysis, SS showed statistically larger increases in NK cells from t7–t16 than MID (p = 0.012). Lastly, sICAM-1 concentrations were associated with changes in CD45RA−CDRO+CD4+ cells (r = − 0.656, p = 0.08). Conclusion These results indicate that intensified training in swimmers resulted in transient changes in T and NK cells. Further, NK cells are sensitive to high training volumes. Lastly, sICAM-1 concentrations may be associated with the migration and maturation of CD4+ cells in athletes.

Biomarkers in vesicoureteral reflux: an overview

Aim: This article aimed to review the role of cytokines, chemokines, growth factors and cellular adhesion molecules as biomarkers for vesicoureteral reflux (VUR) and reflux nephropathy (RN). Methods: We reviewed articles from 1979 onward by searching PubMed and Scopus utilizing the combination of words: ‘VUR’ or ‘RN’ and each one of the biomarkers. Results: Genetic, inflammatory, fibrogenic, environmental and epigenetic factors responsible for renal scarring need to be better understood. TGF-β, IL-10, IL-6, IL-8 and TNF seem to exert a role in VUR particularly in RN based on the current literature. Serum levels of procalcitonin have been also associated with high-grade VUR and RN. These molecules should be more intensively evaluated as potential biomarkers for renal scarring in VUR. Conclusion: Further studies are necessary to define which molecules will really be of utility in clinical decisions and as therapeutic targets for VUR and RN.

Cardiovascular Changes Related to Metabolic Syndrome: Evidence in Obese Zucker Rats

Metabolic syndrome (MetS) is a predictor of cardiovascular diseases, commonly associated with oxidative stress and inflammation. However, the pathogenic mechanisms are not yet fully elucidated. The aim of the study is to evaluate the oxidative status and inflammation in the heart of obese Zucker rats (OZRs) and lean Zucker rats (LZRs) at different ages. Morphological and morphometric analyses were performed in the heart. To study the oxidative status, the malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), protein oxidation, and antioxidant enzymes were measured in plasma and heart. To elucidate the inflammatory markers involved, immunohistochemistry and Western blot were performed for cellular adhesion molecules and proinflammatory cytokines. OZRs were characterized by hypertension, hyperlipidemia, hyperglycemia, and insulin resistance. The obesity increased MDA and decreased the activities of superoxide dismutase (SOD) in plasma as well as in the heart, associated with cardiomyocytes hypertrophy. OxyBlot in plasma and in heart showed an increase of oxidativestate proteins in OZRs. Vascular cell adhesion molecule-1, interleukin-6, and tumor necrosis factor-α expressions in OZRs were higher than those of LZRs. However, these processes did not induce apoptosis or necrosis of cardiomyocytes. Thus, MetS induces the lipid peroxidation and decreased antioxidant defense that leads to heart tissue changes and coronary inflammation.