Body-wide genetic deficiency of poly(ADP-ribose) polymerase 14 sensitizes mice to colitis.

Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract affecting millions of people. Here, we investigated the expression and functions of poly(ADP-ribose) polymerase 14 (Parp14), an important regulatory protein in immune cells, with an IBD patient cohort as well as two mouse colitis models, that is, IBD-mimicking oral dextran sulfate sodium (DSS) exposure and oral Salmonella infection. Parp14 was expressed in the human colon by cells in the lamina propria, but, in particular, by the epithelial cells with a granular staining pattern in the cytosol.

Estrogen deprivation and estrogen receptor α antagonism decrease DSS colitis in female mice.

The association of hormonal contraception with increased risk of inflammatory bowel disease (IBD) observed in females suggests involvement of ovarian hormones, such as estradiol, and the estrogen receptors in the progression of intestinal inflammation. Here, we investigated the effects of prophylactic SERM2 and estradiol supplementation in dextran sulfate sodium-induced colitis using mice with intact ovaries and ovariectomized (OVX) female mice. We found that graded colitis score was threefold reduced in the OVX mice, compared to mice with intact ovaries.

Improved breast milk proteome coverage by DIA based LC-MS/MS method.

The breast milk composition includes a multitude of bioactive factors such as viable cells, lipids and proteins. Measuring the levels of specific proteins in breast milk plasma can be challenging because of the large dynamic range of protein concentrations and the presence of interfering substances. Therefore, most proteomic studies of breast milk have been able to identify under 1000 proteins.

The keratin-desmosome scaffold of internal epithelia in health and disease - The plot is thickening.

Keratin (K) intermediate filaments are attached to desmosomes and constitute the orchestrators of epithelial cell and tissue architecture. While their relevance in the epidermis is well recognized, our review focuses on their emerging importance in internal epithelia. The significance of keratin-desmosome scaffolds (KDSs) in the intestine is highlighted by transgenic mouse models and individuals with inflammatory bowel disease who display profound KDS alterations.

Defining a timeline of colon pathologies after keratin 8 loss: rapid crypt elongation and diarrhea are followed by epithelial erosion and cell exfoliation.

Keratins are epithelial intermediate filament proteins that play a crucial role in cellular stress protection, with K8 being the most abundant in the colon. The intestinal epithelial-specific K8-deficient mouse model (K8;Villin-Cre) exhibits characteristics of inflammatory bowel disease, including diarrhea, crypt erosion, hyperproliferation, and decreased barrier function. Nevertheless, the order in which these events occur and whether they are a direct cause of K8 loss or a consequence of one event inducing another remains unexplored.

Liposome-encapsulated zoledronate increases inflammatory macrophage population in TNBC tumours.

Background: Tumour associated macrophages (TAMs) are important players in breast tumour progression and metastasis. Clinical and preclinical evidence suggests a role for zoledronate (ZOL) in breast cancer metastasis prevention. Further, zoledronate is able to induce inflammatory activation of monocytes and macrophages, which can be favourable in cancer treatments.

Keratin 7 expression in different anatomical parts of colonic epithelium in inflammatory bowel diseases and its prognostic value: a 3-year follow-up study.

The diagnosis of inflammatory bowel diseases (IBD) may be challenging and their clinical course, characterized by relapses and spontaneous or drug-induced remissions, is difficult to predict. Novel prognostic biomarkers are needed. Keratin 7 (K7) is a cytoskeletal intermediate filament protein which is not normally expressed in the colonic epithelium.

The Effect of a Fish Oil and/or Probiotic Intervention from Early Pregnancy Onwards on Colostrum Immune Mediators: A Randomized, Placebo-Controlled, Double-Blinded Clinical Trial in Overweight/Obese Mothers.

Scope: Modifying the composition of colostrum by external factors may provide opportunities to improve the infant's health. Here, we evaluated how fish oil and/or probiotics supplementation modify concentrations of colostrum immune mediators and their associations with perinatal clinical factors on mothers with overweight/obesity.

Methods And Results: Pregnant women were randomized in a double-blind manner into four intervention groups, and the supplements were consumed daily from early pregnancy onwards.

Colonocyte keratin 7 is expressed de novo in inflammatory bowel diseases and associated with pathological changes and drug-resistance.

The clinical course of IBD, characterized by relapses and remissions, is difficult to predict. Initial diagnosis can be challenging, and novel disease markers are needed. Keratin 7 (K7) is a cytoskeletal intermediate filament protein not expressed in the colonic epithelium but has been reported in IBD-associated colorectal tumors.

Targeted deletion of keratin 8 in intestinal epithelial cells disrupts tissue integrity and predisposes to tumorigenesis in the colon.

Keratin 8 (K8) is the main intestinal epithelial intermediate filament protein with proposed roles for colonic epithelial cell integrity. Here, we used mice lacking K8 in intestinal epithelial cells (floxed K8 and Villin-Cre1000 and Villin-CreER) to investigate the cell-specific roles of intestinal epithelial K8 for colonocyte function and pathologies. Intestinal epithelial K8 deletion decreased K8 partner proteins, K18-K20, 75-95%, and the remaining keratin filaments were located at the colonocyte apical regions with type II K7, which decreased 30%.

CC chemokine ligand 2 (CCL2) stimulates aromatase gene expression in mammary adipose tissue.

Obesity is a risk factor for postmenopausal breast cancer. Obesity-related inflammation upregulates aromatase expression, the rate-limiting enzyme for estrogen synthesis, in breast adipose tissue (BAT), increasing estrogen production and cancer risk. The regulation of aromatase gene (CYP19A1) in BAT is complex, and the mechanisms linking obesity and aromatase dysregulation are not fully understood.

An In Vitro Co-Culture Model of Bone Marrow Mesenchymal Stromal Cells and Peripheral Blood Mononuclear Cells Promotes the Differentiation of Myeloid Angiogenic Cells and Pericyte-Like Cells.

Mesenchymal stromal cells (MSCs) are known to stimulate the survival and growth of endothelial cells (ECs) by producing paracrine signals, as well as to differentiate into pericytes and thereby support blood vessel formation and stability. On the other hand, cells with an EC-like phenotype have been found within the CD14 and CD34 cell populations of peripheral blood (PB) mononuclear cells (MNCs). The aim of this study was to investigate the proangiogenic differentiation potential of human MSC-MNC co-cultures.

Keratin intermediate filaments in the colon: guardians of epithelial homeostasis.

Keratin intermediate filament proteins are major cytoskeletal components of the mammalian simple layered columnar epithelium in the gastrointestinal tract. Human colon crypt epithelial cells express keratins 18, 19 and 20 as the major type I keratins, and keratin 8 as the type II keratin. Keratin expression patterns vary between species, and mouse colonocytes express keratin 7 as a second type II keratin.

Novel Selective Estrogen Receptor Modulator Ameliorates Murine Colitis.

Estrogen-receptor-mediated signaling has been suggested to decrease the inflammatory response in monocyte macrophages. Previously, we showed that a novel selective estrogen receptor modulator (SERM2) promotes anti-inflammatory phenotype of monocytes in vitro. In this study, we demonstrate the potential of SERM2 in amelioration of colitis.

Increase in serum Interleukin-10 does not alleviate pro-inflammatory MCP-1 production in obese pregnancies.

Maternal cytokine profiles during pregnancy are characterized by significant deviations, varying substantially between gestational time points and tissues. Obesity, in turn, is linked with low-grade inflammation in adipose tissue and increased concentrations of systemic inflammatory mediators. However, the balance of pro- and anti-inflammatory cytokines in obese pregnancy has remained elusive.

SERMs Promote Anti-Inflammatory Signaling and Phenotype of CD14+ Cells.

Signaling via estrogen receptors (ER) is recognized as an essential part of the immune regulation, and ER-mediated signaling is involved in autoimmune reactions. Especially ERα activation in immune cells has been suggested to skew cytokine production toward Th2/M2-type mediators, which can have protective effect on inflammatory diseases and reduce Th1 and Th17 responses. These effects are caused by increased alternative activation of macrophages and changes in the activation of different T cell populations.

Placental structural abnormalities have detrimental hemodynamic consequences in a rat model of maternal hyperglycemia.

Introduction: Human type 1 diabetic pregnancy is associated with placental structural and hemodynamic abnormalities. We hypothesized that in rat fetuses of hyperglycemic dams, placental and fetal blood flow velocity waveforms demonstrate compromised hemodynamics when compared to control fetuses, and these hemodynamic parameters correlate with placental structural abnormalities at near term gestation.

Methods: Streptozotocin-induced maternal hyperglycemia group comprised 10 dams with 107 fetuses and the control group 20 dams with 219 fetuses.

Novel Lignan and stilbenoid mixture shows anticarcinogenic efficacy in preclinical PC-3M-luc2 prostate cancer model.

Prostate cancer is the most common cancer of men in the Western world, and novel approaches for prostate cancer risk reduction are needed. Plant-derived phenolic compounds attenuate prostate cancer growth in preclinical models by several mechanisms, which is in line with epidemiological findings suggesting that consumption of plant-based diets is associated with low risk of prostate cancer. The objective of this study was to assess the effects of a novel lignan-stilbenoid mixture in PC-3M-luc2 human prostate cancer cells in vitro and in orthotopic xenografts.

Galactoglucomannan extracted from spruce (Picea abies) as a carbohydrate source for probiotic bacteria.

A prebiotic is a nonviable food component that confers a health benefit on the host associated with modulation of the microbiota. Hemicelluloses are the second most common group of polysaccharides in nature and they occur in plant cell walls. The predominant hemicellulose in softwood species is galactoglucomannan, and based on its chemical structure and information available about similar saccharides, galactoglucomannan may be postulated to have prebiotic properties.

Determination of gas phase triacetone triperoxide with aspiration ion mobility spectrometry and gas chromatography-mass spectrometry.

Aspiration ion mobility spectrometry (IMS) has been used for the first time to screen 3,3,6,6,9,9-hexamethyl-1,2,4,5,7,8-hexaoxacyclononane explosive, the most commonly known as triacetone triperoxide (TATP). Gaseous TATP was generated from synthesized solid compound, sublimed and directed to a portable chemical detection system comprised of an aspiration-type IMS detector and six semiconductor sensors. Different unknown TATP gas phase concentrations were produced and corresponding IMS and semiconductor responses were measured.