Galanin (GAL) is an important neurotransmitter released by the enteric nervous system (ENS) neurons located in the muscularis externa and submucosa enteric plexuses that acts by binding to GAL receptors 1, 2 and 3 (GALR1, 2 and 3). In our previous studies, the GAL immunoexpression was compared in colorectal cancer (CRC) tissue and the adjacent parts of the large intestine wall including myenteric and submucosal plexuses. Recently we have also found that expression levels of GALR1 and GALR3 proteins are elevated in CRC tissue as compared with their expression in epithelial cells of unchanged mucosa. Moreover, higher GALR3 immunoreactivity in CRC cells correlated with better prognosis of CRC patients. To understand the distribution of GALRs in enteric plexuses distal and close to CRC invasion, in the present study we decided to evaluate GALRs expression within the myenteric and submucosal plexuses located proximally and distally to the cancer invasion and correlated the GALRs expression levels with the clinico-pathological data of CRC patients. The immunohistochemical and immunofluorescent methods showed only slightly decreased immunoexpression of GALR1 and GALR3 in myenteric plexuses close to cancer but did not reveal any correlation in the immunoexpression of all three GAL receptors in myenteric plexuses and tumour progression. No significant changes were found between the expression levels of GALRs in submucosal plexuses distal and close to the tumour. However, elevated GALR1 expression in submucosal plexuses in vicinity of CRC correlated with poor prognosis, higher tumour grading and shorter overall survival. When myenteric plexuses undergo morphological and functional alterations characteristic for atrophy, GALRs maintain or only slightly decrease their expression status. In contrast, the correlation between high expression of GALR1 in the submucosal plexuses and overall survival of CRC patients suggest that GAL and GALRs can act as a components of local neuro-paracrine pro-proliferative pathways accelerating the invasion and metastasis of cancer cell. The obtained results suggest an important role of GALR1 in submucosal plexuses function during the progression of CRC and imply that GALR1 expression in submucosal plexuses of ENS could be an important predictive factor for CRC progression.

Colorectal cancer (CRC) is the second most common cause of cancer in women and the third in men. The postoperative pathomorphological evaluation of patients with CRC is extremely important for future therapeutic decisions. Although our previous studies demonstrated high galanin (GAL) presence within tumor tissue and an elevated concentration of GAL in the serum of CRC patients, to date, there is a lack of data regarding GAL receptor (GalR) protein expression in CRC cells. Therefore, the aim of this study was to evaluate the presence of all three types of GalRs (GalR1, GalR2 and GalR3) within epithelial cells of the human colon and CRC tissue with the use of the immunohistochemical method and to correlate the results with the clinical-pathological data. We found stronger immunoreactivity of GalR1 and GalR3 in CRC cells compared to epithelial cells of the unchanged mucosa of the large intestine. No differences in the GalR2 protein immunoreactivity between the studied tissues were noted. We also found that the increased immunoexpression of the GalR3 in CRC tissue correlated with the better prognosis and longer survival (p < 0.0079) of CRC patients (n = 55). The obtained results suggest that GalR3 may play the role of a prognostic factor for CRC patients. Based on data from the TCGA-COAD project deposited in the GDC Data Portal, we also found that GalR mRNA in cancer samples and the adjacent normal tissue did not correlate with immunoexpression of the GalR proteins in CRC cells and epithelial cells of the unchanged mucosa.

Context: The appropriate course of angiogenesis in the endometrium is crucial for pregnancy establishment and maintenance. Very little is known about the factors linking vessel formation and immune system functioning. Aims: We hypothesised that chemerin, an adipokine known for its involvement in the regulation of energy balance and immunological functions, may act as a potent regulator of endometrial angiogenesis during early pregnancy in pigs. Methods: Porcine endometrial tissue explants were obtained from pregnant pigs on days 10–11, 12–13, 15–16 and 27–28, and on days 10–12 of the oestrous cycle. The explants were in vitro cultured for 24 h in the presence of chemerin (100, 200 ng/mL) or in medium alone (control). We evaluated the in vitro effect of chemerin on the secretion of vascular endothelial growth factors A–D (VEGF-A–D), placental growth factor (PlGF), basic fibroblast growth factor (bFGF) and angiopoietin 1 and 2 (ANG-1, ANG-2) with the ELISA method. The protein abundance of angiogenesis-related factor receptors, VEGF receptors 1–3 (VEGFR1–3), FGF receptors 1 and 2 (FGFR1–2) and ANG receptor (TIE2) was evaluated with the Western blot (WB) method. We also analysed the influence of chemerin on the phosphorylation of AMPK using WB. Key results: We found that in the studied endometrial samples, chemerin up-regulated the secretion of VEGF-A, VEGF-B and PlGF, and protein expression of VEGFR3. The adipokine caused a decrease in VEGF-C, VEGF-D and ANG-1 release. Chemerin effect on bFGF and ANG-2 secretion, and protein content of VEGFR1, VEGFR2, FGFR1, FGFR2 and TIE2 were dependent on the stage of pregnancy. Chemerin was found to down-regulate AMPK phosphorylation. Conclusions: The obtained in vitro results suggest that chemerin could be an important factor in the early pregnant uterus by its influence on angiogenic factors’ secretion and signalling. Implications: The obtained results on the role of chemerin in the process of endometrial angiogenesis may, in the long term perspective, contribute to the elaboration of more effective methods of modifying reproductive processes and maintaining energy homeostasis in farm animals.

Sclerostin might play a role in atherosclerosis development. This study aimed to analyze the impact of baseline sclerostin levels on 9-year outcomes in patients without significant renal function impairment and undergoing coronary angiography. The primary study endpoint was the rate of major cardiovascular events (MACE), defined as a combined rate of myocardial infarction (MI), stroke, or death at 9 years. We included 205 patients with a mean age of 62.9 ± 0.6 years and 70.2% male. Median serum sclerostin concentration was 133.22 pg/mL (IQR 64.0–276.17). At 9 years, in the whole population, the rate of MACE was 34.1% (n = 70), MI: 11.2% (n = 23), stroke: 2.4% (n = 5), and death: 20.5% (n = 42). In the high sclerostin (>median) group, we observed statistically significant higher rates of MACE and death: 25.2% vs. 43.1% (HR 1.75, 95% CI 1.1–2.10, p = 0.02) and 14.6% vs. 26.5% (HR 1.86, 95% CI 1.02–3.41, p = 0.049), respectively. Similar relationships were observed in patients with chronic coronary syndrome and SYNTAX 0–22 subgroups. Our results suggest that sclerostin assessment might be useful in risk stratification, and subjects with higher sclerostin levels might have a worse prognosis.