Epithelial N-cadherin and nuclear β-catenin are up-regulated during early development of human lung

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to analyze the cell-specific expression of E- and N-cadherin and β-catenin in developing human lung tissues from 12 to 40 weeks of gestation.</p> <p>Methods</p> <p>Fortyseven cases of developing human lung including pseudoglandular, canalicular, saccular and alveolar periods were analyzed by immunohistochemisty for E- and N-cadherin and β-catenin and twentyone cases were also investigated by RT-PCR for E- and N-cadherin and β-catenin. For identifying the lung cells, the sections were also stained with antibodies against thyroid transcription factor-1 (TTF-1) and caveolin-1. Normal adult lung tissue was used as a control.</p> <p>E-cadherin was strongly expressed in epithelium of bronchi and large bronchioles from week 12 onwards and it was also positive in alveoli in pretype II cells and type II cells. N-cadherin was present in most of the epithelial cells of bronchi and the largest bronchioles during the pseudo-glandular and canalicular periods. N-cadherin was not detected in epithelium of developing alveoli. β-catenin was strongly membrane-bound and positively expressed in bronchial epithelium from week 12 to week 40; it showed nuclear positivity in both developing airway epithelium and in the cells underneath the epithelium during pseudo-glandular period and to a lesser degree also in the canalicular period. β-catenin was positive in pretype II cells as well as in type I and type II pneumocytes within alveoli.</p> <p>RT-PCR analyses revealed detectable amounts of RNAs of E- and N-cadherin and β-catenin in all cases studied. The amounts of RNAs were higher in early stages of gestation.</p> <p>Conclusions</p> <p>E-cadherin is widely expressed in bronchial and alveolar epithelial cells. N-cadherin exhibit extensive epithelial positivity in bronchial epithelial cells during early lung development. The presence of β-catenin was observed in several cell types with a distinct location in tissue and cells in various gestational stages, indicating that it possesses several roles during lung development. The expressions of protein and mRNAs of E- and N-cadherin and β-catenin were higher in early gestation compared to of the end. Moreover, the expressions of these factors were higher during the lung development than in the adult human lung.</p

Niche matters : The comparison between bone marrow stem cells and endometrial stem cells and stromal fibroblasts reveal distinct migration and cytokine profiles in response to inflammatory stimulus

Objective Intrinsic inflammatory characteristics play a pivotal role in stem cell recruitment and homing through migration where the subsequent change in niche has been shown to alter these characteristics. The bone marrow mesenchymal stem cells (bmMSCs) have been demonstrated to migrate to the endometrium contributing to the stem cell reservoir and regeneration of endometrial tissue. Thus, the aim of the present study was to compare the inflammation-driven migration and cytokine secretion profile of human bmMSCs to endometrial mesenchymal stem cells (eMSCs) and endometrial fibroblasts (eSFs). Materials and methods The bmMSCs were isolated from bone marrow aspirates through culturing, whereas eMSCs and eSFs were FACS-isolated. All cell types were tested for their surface marker, proliferation profiles and migration properties towards serum and inflammatory attractants. The cytokine/chemokine secretion profile of 35 targets was analysed in each cell type at basal level along with lipopolysaccharide (LPS)-induced state. Results Both stem cell types, bmMSCs and eMSCs, presented with similar stem cell surface marker profiles as well as possessed high proliferation and migration potential compared to eSFs. In multiplex assays, the secretion of 16 cytokine targets was detected and LPS stimulation expanded the cytokine secretion pattern by triggering the secretion of several targets. The bmMSCs exhibited higher cytokine secretion of vascular endothelial growth factor (VEGF)A, stromal cell-derived factor-1 alpha (SDF)-1 alpha, interleukin-1 receptor antagonist (IL-1RA), IL-6, interferon-gamma inducible protein (IP)-10, monocyte chemoattractant protein (MCP)1, macrophage inflammatory protein (MIP) 1 alpha and RANTES compared to eMSCs and/or eSFs after stimulation with LPS. The basal IL-8 secretion was higher in both endometrial cell types compared to bmMSCs. Conclusion Our results highlight that similar to bmMSCs, the eMSCs possess high migration activity while the differentiation process towards stromal fibroblasts seemed to result in loss of stem cell surface markers, minimal migration activity and a subtler cytokine profile likely contributing to normal endometrial functionPeer reviewe

Two novel direct SPIO labels and in vivo MRI detection of labeled cells after acute myocardial infarct

Background: Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide. Cellular decay due hypoxia requires rapid and validated methods for possible therapeutic cell transplantation. Purpose: To develop direct and rapid superparamagnetic iron oxide (SPIO) cell label for a large-animal model and to assess in vivo cell targeting by magnetic resonance imaging (MRI) in an experimental AMI model. Material and Methods: Bone marrow mononuclear cells (BMMNCs) were labeled with SPIO particles using two novel direct labeling methods (rotating incubation method and electroporation). Labeling, iron incorporation in cells and label distribution, cellular viability, and proliferation were validated in vitro. An AMI porcine model was used to evaluate the direct labeling method (rotating incubation method) by examining targeting of labeled BMMNCs using MRI and histology. Results: Labeling (1 h) did not alter either cellular differentiation potential or viability of cells in vitro. Cellular relaxation values at 9.4 T correlated with label concentration and MRI at 1.5 T showing 894% signal reduction compared with non-labeled cells in vitro. In vivo, a high spatial correlation between MRI and histology was observed. The extent of macroscopic pathological myocardial changes (hemorrhage) correlated with altered function detected on MRI. Conclusion: We demonstrated two novel direct SPIO labeling methods and demonstrated the feasibility of clinical MRI for monitoring targeting of the labeled cells in animal models of AMI.Peer reviewe

Women with polycystic ovary syndrome present with altered endometrial expression of stanniocalcin-1

Stanniocalcin-1 (STC-1) is a pro-survival factor that protects tissues against stressors, such as hypoxia and inflammation. STC-1 is co-expressed with the endometrial receptivity markers, and recently endometrial STC-1 was reported to be dysregulated in endometriosis, a condition linked with endometrial progesterone resistance and inflammation. These features are also common in the endometrium in women with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women. Given that women with PCOS present with subfertility, pregnancy complications, and increased risk for endometrial cancer, we investigated endometrial STC-1 expression in affected women. Endometrial biopsy samples were obtained from women with PCOS and controls, including samples from overweight/obese women with PCOS before and after a 3-month lifestyle intervention. A total of 98 PCOS and 85 control samples were used in immunohistochemistry, reverse-transcription polymerase chain reaction, or in vitro cell culture. STC-1 expression was analyzed at different cycle phases and in endometrial stromal cells (eSCs) after steroid hormone exposure. The eSCs were also challenged with 8-bromo-cAMP and hypoxia for STC-1 expression. The findings indicate that STC-1 expression is not steroid hormone mediated although secretory-phase STC-1 expression was blunted in PCOS. Lower expression seems to be related to attenuated STC-1 response to stressors in PCOS eSCs, shown as downregulation of protein kinase A activity. The 3-month lifestyle intervention did not restore STC-1 expression in PCOS endometrium. More studies are warranted to further elucidate the mechanisms behind the altered endometrial STC-1 expression and rescue mechanism in the PCOS endometrium. Summary sentence Endometrial expression of STC-1 in the secretory phase is blunted in women with PCOS, suggesting impaired protection against stress.Peer reviewe

Parent–infant closeness after preterm birth and depressive symptoms : A longitudinal study

Background: Preterm birth increases the risk for postpartum depression in both mothers and fathers, calling for strategies to alleviate and prevent depressive symptoms in parents of preterm infants. The aim of this study was to assess the association between early parent-infant closeness and later depressive symptoms among parents of preterm infants. We hypothesized that longer duration of closeness associate with fewer depressive symptoms in both parents. Methods: This prospective cohort study included 23 neonatal intensive care units (NICUs) from 15 countries in 2018 to 2020. Each unit recruited families with preterm infants aiming to 30 families. The total duration of parents’ presence in the NICU, and separately parent-infant skin-to-skin contact and holding, were measured using a Closeness Diary up to 14  days. The Edinburgh Postnatal Depression Scale (EPDS) was used at discharge and at 4  months corrected age of the infant. Results: The study included 684 mothers and 574 fathers. The median presence was 469   min (Q1 258 and Q3 1,087) per 24   h for the mothers and 259   min (Q1 100 and Q3 540) for the fathers; mean EPDS scores were 9.2 (SD 5.0) and 6.3 (SD 4.4) at discharge and 6.6 (4.7) and 4.3 (4.2) at 4  months, respectively. Parents’ presence and depressive symptoms varied greatly between the units. Parents’ presence as the total measure, or skin-to-skin contact and holding separately, did not associate with depressive symptoms in either mothers or fathers at either time point (adjusted). Conclusion: No association was found between the duration of parent-infant closeness in the neonatal unit and parents’ depressive symptoms. The beneficial effects of family-centered care on parents’ depression seem to be mediated by other elements than parent-infant physical closeness. More research is needed to identify the critical elements which are needed to alleviate parents’ depression after NICU stay.© 2022 Lehtonen, Lilliesköld, De Coen, Toome, Gimeno, Caballero, Tameliene, Laroche, Retpap, Grundt, Van Hoestenberghe, Skene, Pape and Axelin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.fi=vertaisarvioitu|en=peerReviewed

Parent-infant closeness after preterm birth and depressive symptoms: A longitudinal study

Background: Preterm birth increases the risk for postpartum depression in both mothers and fathers, calling for strategies to alleviate and prevent depressive symptoms in parents of preterm infants. The aim of this study was to assess the association between early parent-infant closeness and later depressive symptoms among parents of preterm infants. We hypothesized that longer duration of closeness associate with fewer depressive symptoms in both parents.Methods: This prospective cohort study included 23 neonatal intensive care units (NICUs) from 15 countries in 2018 to 2020. Each unit recruited families with preterm infants aiming to 30 families. The total duration of parents’ presence in the NICU, and separately parent-infant skin-to-skin contact and holding, were measured using a Closeness Diary up to 14  days. The Edinburgh Postnatal Depression Scale (EPDS) was used at discharge and at 4  months corrected age of the infant.Results: The study included 684 mothers and 574 fathers. The median presence was 469   min (Q1 258 and Q3 1,087) per 24   h for the mothers and 259   min (Q1 100 and Q3 540) for the fathers; mean EPDS scores were 9.2 (SD 5.0) and 6.3 (SD 4.4) at discharge and 6.6 (4.7) and 4.3 (4.2) at 4  months, respectively. Parents’ presence and depressive symptoms varied greatly between the units. Parents’ presence as the total measure, or skin-to-skin contact and holding separately, did not associate with depressive symptoms in either mothers or fathers at either time point (adjusted).Conclusion: No association was found between the duration of parent-infant closeness in the neonatal unit and parents’ depressive symptoms. The beneficial effects of family-centered care on parents’ depression seem to be mediated by other elements than parent-infant physical closeness. More research is needed to identify the critical elements which are needed to alleviate parents’ depression after NICU stay.</p

VII Scandinavian Copd Research Symposium, Holmenkollen, Oslo 18th-19th November 2016

Peer reviewe

Localization and regulation of peroxiredoxins in human lung and lung diseases

Abstract Reactive oxygen species (ROS) can cause severe damage to cells and organs but they are also important mediators of inflammatory responses and cellular signalling. Due to the significant role of ROS, the cells have evolved a broad antioxidative system to regulate the concentration of these species. Peroxiredoxins (Prxs) are enzymes that participate in the regulation of the cellular redox-homeostasis by detoxifying hydrogen peroxide. Prxs are not classified as conventional antioxidant enzymes and their physiological role, whether protective or regulatory, is still unclear. The aim of this project was to study the localization and regulation of Prxs in normal human lung and also their role in selected lung disorders (pulmonary sarcoidosis, pleural mesothelioma, lung carcinomas and chronic obstructive disorder, COPD). Additionally the expression of thioredoxin (Trx) and thioredoxin reductase (TrxR) was analysed in the lung of smokers and COPD patients. These enzymes are important reductants in cell and Prxs are one of their targets. Lung is an important organ in the field of ROS and antioxidant research since it is especially vulnerable to exogenous oxidative stress caused by pollutants, cigarette smoke and also by high oxygen pressure. The results showed that all six human Prxs were expressed in healthy human lung but in a cell-specific manner. The most prominent expression was detected in the epithelium and in macrophages, the cells most prone to oxidative stress. There were also differences in subcellular locations of Prxs. The expression of Prxs in non-malignant lung diseases (pulmonary sarcoidosis and COPD) and in smoker's lung was very similar with that in normal lung. Higher expression of Prx V and VI was detected in a subpopulation of macrophages sampled from COPD patients' lung. In contrast, Trx expression was induced in the bronchial epithelium of smoker's lung. Differences in the expression compared to normal lung were seen in lung malignancies (pleural mesothelioma and lung carcinomas). Interestingly, different Prxs were highly expressed in different types of carcinomas. In pleural mesothelioma, all Prxs except Prx IV were highly expressed when compared to normal pleura, in adenocarcinoma Prxs I, II, VI and especially IV, and in squamous cell carcinoma Prxs I, II and IV were upregulated. Tests performed on cultured cells in vitro revealed only a minor increase in the Prx expression after severe oxidant stress in malignant lung cell line originating from alveolar type II pneumocytes (A549) or non-malignant cell line derived from bronchial epithelium. None of the tested growth factors or cytokines affected Prx expression or oxidation state, but severe oxidant stress influenced remarkably the oxidation state of the Prxs

Bronchoalveolar-Lavage-Derived Fibroblast Cell Lines Provide Tools for Investigating Various Interstitial Lung Diseases

Bronchoalveolar lavage (BAL) is an important diagnostic and research tool for the investigation of various lung diseases. In addition to inflammatory and epithelial cells, BAL fluid may contain a small number of stromal cells, such as fibroblasts. During the past 30 years, a number of research groups have cultured BAL-derived fibroblasts for several passages in vitro. In addition to fibroblasts, these cultures have been reported to contain fibrocytes, myofibroblasts, and stem cells. We aim to present a summary of studies that have cultured stromal cells from BAL fluid