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1.
Philos Trans R Soc Lond B Biol Sci ; 377(1865): 20210266, 2022 12 05.
Article En | MEDLINE | ID: mdl-36252212

Insects comprise more than a million species and many authors have attempted to explain this success by evolutionary innovations. A much overlooked evolutionary novelty of insects is the serosa, an extraembryonic epithelium around the yolk and embryo. We have shown previously that this epithelium provides innate immune protection to eggs of the beetle Tribolium castaneum. It remained elusive, however, whether this immune competence evolved in the Tribolium lineage or is ancestral to all insects. Here, we expand our studies to two hemimetabolous insects, the bug Oncopeltus fasciatus and the swarming grasshopper Locusta migratoria. For Oncopeltus, RNA sequencing reveals an extensive response upon infection, including the massive upregulation of antimicrobial peptides (AMPs). We demonstrate antimicrobial activity of these peptides using in vitro bacterial growth assays and describe two novel AMP families called Serosins and Ovicins. For both insects, quantitative polymerase chain reaction shows immune competence of the eggs when the serosa is present, and in situ hybridizations demonstrate that immune gene expression is localized in the serosa. This first evidence from hemimetabolous insect eggs suggests that immune competence is an ancestral property of the serosa. The evolutionary origin of the serosa with its immune function might have facilitated the spectacular radiation of the insects. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.


Anti-Infective Agents , Heteroptera , Tribolium , Animals , Anti-Infective Agents/metabolism , Immunity , Insect Proteins/genetics , Insect Proteins/metabolism , Insecta/metabolism , Serous Membrane/metabolism , Tribolium/genetics
2.
Philos Trans R Soc Lond B Biol Sci ; 377(1865): 20210265, 2022 12 05.
Article En | MEDLINE | ID: mdl-36252222

The conservation of gene networks that specify and differentiate distinct tissues has long been a subject of great interest to evolutionary developmental biologists, but the question of how pre-existing tissue-specific developmental trajectories merge is rarely asked. During the radiation of flies, two extraembryonic epithelia, known as serosa and amnion, evolved into one, called amnioserosa. This unique extraembryonic epithelium is found in fly species of the group Schizophora, including the genetic model organism Drosophila melanogaster, and has been studied in depth. Close relatives of this group develop a serosa and a rudimentary amnion. The scuttle fly Megaselia abdita has emerged as an excellent model organism to study this extraembryonic tissue organization. In this review, development and functions of the extraembryonic tissue complements of Drosophila and Megaselia are compared. It is concluded that the amnioserosa combines cells, genetic pathway components and functions that were previously associated either with serosa development or amnion development. The composite developmental trajectory of the amnioserosa raises the question of whether merging tissue-specific gene networks is a common evolutionary process. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.


Amnion , Drosophila melanogaster , Amnion/metabolism , Animals , Drosophila/genetics , Drosophila melanogaster/genetics , Embryo, Nonmammalian/metabolism , Epithelium , Serous Membrane/metabolism
3.
Philos Trans R Soc Lond B Biol Sci ; 377(1865): 20210268, 2022 12 05.
Article En | MEDLINE | ID: mdl-36252225

It is fascinating that the amnion and serosa/chorion, two extraembryonic (EE) tissues that are characteristic of the amniote vertebrates (mammals, birds and reptiles), have also independently evolved in insects. In this review, we offer the first detailed, macroevolutionary comparison of EE development and tissue biology across these animal groups. Some commonalities represent independent solutions to shared challenges for protecting the embryo (environmental assaults, risk of pathogens) and supporting its development, including clear links between cellular properties (e.g. polyploidy) and physiological function. Further parallels encompass developmental features such as the early segregation of the serosa/chorion compared to later, progressive differentiation of the amnion and formation of the amniotic cavity from serosal-amniotic folds as a widespread morphogenetic mode across species. We also discuss common developmental roles for orthologous transcription factors and BMP signalling in EE tissues of amniotes and insects, and between EE and cardiac tissues, supported by our exploration of new resources for global and tissue-specific gene expression. This highlights the degree to which general developmental principles and protective tissue features can be deduced from each of these animal groups, emphasizing the value of broad comparative studies to reveal subtle developmental strategies and answer questions that are common across species. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.


Amnion , Insecta , Amnion/metabolism , Animals , Mammals , Morphogenesis/physiology , Serous Membrane/metabolism , Transcription Factors/metabolism
4.
Int J Mol Sci ; 22(21)2021 Oct 27.
Article En | MEDLINE | ID: mdl-34769019

Liver transplantation is the most effective treatment for end-stage cirrhosis. However, due to serious donor shortages, new treatments to replace liver transplantation are sorely needed. Recent studies have focused on novel therapeutic methods using hepatocytes and induced pluripotent stem cells, we try hard to develop methods for transplanting these cells to the liver surface. In the present study, we evaluated several methods for their efficiency in the detachment of serous membrane covering the liver surface for transplantation to the liver surface. The liver surface of dipeptidyl peptidase IV (DPPIV)-deficient rats in a cirrhosis model was detached by various methods, and then fetal livers from DPPIV-positive rats were transplanted. We found that the engraftment rate and area as well as the liver function were improved in rats undergoing transplantation following serous membrane detachment with an ultrasonic homogenizer, which mimics the Cavitron Ultrasonic Surgical Aspirator® (CUSA), compared with no detachment. Furthermore, the bleeding amount was lower with the ultrasonic homogenizer method than with the needle and electric scalpel methods. These findings provide evidence that transplantation to the liver surface with serous membrane detachment using CUSA might contribute to the development of new treatments for cirrhosis using cells or tissues.


Liver Cirrhosis/pathology , Liver/pathology , Serous Membrane/pathology , Animals , Dipeptidyl Peptidase 4/metabolism , Disease Models, Animal , Female , Hepatectomy/methods , Hepatocytes/metabolism , Hepatocytes/pathology , Liver/metabolism , Liver Cirrhosis/metabolism , Liver Transplantation/methods , Rats , Rats, Inbred F344 , Serous Membrane/metabolism , Ultrasonic Therapy/methods , Ultrasonics/methods
5.
Am J Physiol Lung Cell Mol Physiol ; 320(5): L845-L879, 2021 05 01.
Article En | MEDLINE | ID: mdl-33655758

Airway submucosal gland serous cells are important sites of fluid secretion in conducting airways. Serous cells also express the cystic fibrosis (CF) transmembrane conductance regulator (CFTR). Protease-activated receptor 2 (PAR-2) is a G protein-coupled receptor that activates secretion from intact airway glands. We tested if and how human nasal serous cells secrete fluid in response to PAR-2 stimulation using Ca2+ imaging and simultaneous differential interference contrast imaging to track isosmotic cell shrinking and swelling reflecting activation of solute efflux and influx pathways, respectively. During stimulation of PAR-2, serous cells exhibited dose-dependent increases in intracellular Ca2+. At stimulation levels >EC50 for Ca2+, serous cells simultaneously shrank ∼20% over ∼90 s due to KCl efflux reflecting Ca2+-activated Cl- channel (CaCC, likely TMEM16A)-dependent secretion. At lower levels of PAR-2 stimulation (

Chlorides/metabolism , Cystic Fibrosis Transmembrane Conductance Regulator/metabolism , Exocrine Glands/pathology , Pseudomonas Infections/microbiology , Receptor, PAR-2/metabolism , Respiratory Mucosa/pathology , Serous Membrane/pathology , Calcium/metabolism , Cells, Cultured , Cyclic AMP/metabolism , Exocrine Glands/metabolism , Exocrine Glands/microbiology , Humans , Pseudomonas aeruginosa/isolation & purification , Respiratory Mucosa/metabolism , Respiratory Mucosa/microbiology , Serous Membrane/metabolism , Serous Membrane/microbiology
6.
Nat Commun ; 11(1): 5604, 2020 11 05.
Article En | MEDLINE | ID: mdl-33154375

Many animal embryos pull and close an epithelial sheet around the ellipsoidal egg surface during a gastrulation process known as epiboly. The ovoidal geometry dictates that the epithelial sheet first expands and subsequently compacts. Moreover, the spreading epithelium is mechanically stressed and this stress needs to be released. Here we show that during extraembryonic tissue (serosa) epiboly in the insect Tribolium castaneum, the non-proliferative serosa becomes regionalized into a solid-like dorsal region with larger non-rearranging cells, and a more fluid-like ventral region surrounding the leading edge with smaller cells undergoing intercalations. Our results suggest that a heterogeneous actomyosin cable contributes to the fluidization of the leading edge by driving sequential eviction and intercalation of individual cells away from the serosa margin. Since this developmental solution utilized during epiboly resembles the mechanism of wound healing, we propose actomyosin cable-driven local tissue fluidization as a conserved morphogenetic module for closure of epithelial gaps.


Epithelium/embryology , Gastrulation/physiology , Insecta/embryology , Actomyosin/metabolism , Animals , Biomechanical Phenomena , Cell Movement , Epithelium/metabolism , Insect Proteins/metabolism , Morphogenesis , Serous Membrane/embryology , Serous Membrane/metabolism , Tribolium/embryology , Wound Healing
7.
Immunol Lett ; 228: 135-141, 2020 12.
Article En | MEDLINE | ID: mdl-33166529

Although not typical lymphoid organs, analysis of the visceral adipose-associated lymphoid tissues has recently substantially expanded our knowledge about the immunological features of these elusive compartments. Recent data have highlighted their considerable complexity in cellular organization and interactions in several biological processes, including adaptive immune responses, tissue plasticity to accommodate mesenchymal stem cells and progenitors, and providing a suitable microenvironment for serosal tumor propagation. This review aims to present a comprehensive view of the adipose-associated lymphoid tissues in local and systemic immune responsiveness, with particular emphasis on the omental and mesenteric lymphoid tissues in the serosal defense of abdominal organs.


Abdominal Fat/immunology , Adaptive Immunity , Lymphoid Tissue/immunology , Serous Membrane/immunology , Abdominal Fat/metabolism , Adipocytes/immunology , Adipocytes/metabolism , Animals , Cell Communication , Humans , Lymphoid Tissue/metabolism , Mesenchymal Stem Cells/immunology , Mesenchymal Stem Cells/metabolism , Myeloid Cells/immunology , Myeloid Cells/metabolism , Peritoneal Neoplasms/immunology , Peritoneal Neoplasms/metabolism , Peritoneal Neoplasms/pathology , Phenotype , Serous Membrane/metabolism
8.
Am J Physiol Gastrointest Liver Physiol ; 318(4): G673-G681, 2020 04 01.
Article En | MEDLINE | ID: mdl-32003605

Impaired manganese (Mn) homeostasis can result in excess Mn accumulation in specific brain regions and neuropathology. Maintaining Mn homeostasis and detoxification is dependent on effective Mn elimination. Specific metal transporters control Mn homeostasis. Human carriers of mutations in the metal transporter ZIP14 and whole body Zip14-knockout (WB-KO) mice display similar phenotypes, including spontaneous systemic and brain Mn overload and motor dysfunction. Initially, it was believed that Mn accumulation due to ZIP14 mutations was caused by impaired hepatobiliary Mn elimination. However, liver-specific Zip14-KO mice did not show systemic Mn accumulation or motor deficits. ZIP14 is highly expressed in the small intestine and is localized to the basolateral surface of enterocytes. Thus, we hypothesized that basolaterally localized ZIP14 in enterocytes provides another route for the elimination of Mn. Using wild-type and intestine-specific Zip14-KO (I-KO) mice, we have shown that ablation of intestinal Zip14 is sufficient to cause systemic and brain Mn accumulation. The lack of intestinal ZIP14-mediated Mn excretion was compensated for by the hepatobiliary system; however, it was not sufficient to maintain Mn homeostasis. When supplemented with extra dietary Mn, I-KO mice displayed some motor dysfunctions and brain Mn accumulation based on both MRI imaging and chemical analysis, thus demonstrating the importance of intestinal ZIP14 as a route of Mn excretion. A defect in intestinal Zip14 expresssion likely could contribute to the Parkinson-like Mn accumulation of manganism.NEW & NOTEWORTHY Mn-induced parkinsonism is recognized as rising in frequency because of both environmental factors and genetic vulnerability; yet currently, there is no cure. We provide evidence in an integrative animal model that basolaterally localized ZIP14 regulates Mn excretion and detoxification and that deletion of intestinal ZIP14 leads to systemic and brain Mn accumulation, providing robust evidence for the indispensable role of intestinal ZIP14 in Mn excretion.


Cation Transport Proteins/metabolism , Gait Disorders, Neurologic/chemically induced , Intestinal Mucosa/metabolism , Manganese/toxicity , Animals , Biological Transport , Brain/metabolism , Brain/pathology , Cation Transport Proteins/genetics , Dose-Response Relationship, Drug , Genotype , Inflammation/chemically induced , Manganese/administration & dosage , Mice , Mice, Knockout , Serous Membrane/metabolism
9.
J Anim Physiol Anim Nutr (Berl) ; 104(3): 776-789, 2020 May.
Article En | MEDLINE | ID: mdl-31985122

High amounts of short-chain fatty acids (SCFAs) occur in the ovine rumen and constitute the animal's main energy source. However, they lead to an acidification of the ruminal epithelium. Therefore, effective intracellular pH (pHi ) regulation by transport proteins like monocarboxylate transporter 1 (MCT1) and Na+ /H+ exchangers (NHEs) is pivotal to ruminants to avoid epithelial damage. SCFAs might function not only as nutrients but also as signalling molecules by activating free fatty acid receptors (FFARs) in the ruminal epithelium and thus influence pHi regulation. FFARs work as nutrient sensors, transducing their information by modulating cyclic adenosine monophosphate (cAMP) levels. We hypothesized that (FFAR-modulated) decreases in cAMP levels stimulate the activity of MCT1 and NHEs in the ruminal epithelium of sheep. We detected two FFARs (GPR109A and FFAR2) immunohistochemically in the ovine ruminal epithelium. Administration of 10 mM butyrate to Ussing chamber-mounted epithelia provoked a significant reduction in intraepithelial cAMP levels. However, application of the GPR109A agonist niacin did not affect cAMP levels. MCT1 activity was analysed by measuring transepithelial 14 C-acetate fluxes, which were not inhibited by forskolin-induced increased cAMP levels. The recovery of pHi after acidification was assessed as an indicator of NHE activity in primary cultured ruminal epithelial cells. Recovery was significantly reduced when cells with increased cAMP levels were subjected to the NHE inhibitor 5-(N-ethyl-N-isopropyl)-amiloride (10 µM). Nonetheless, with augmented cAMP levels alone, NHE activity tended to decline. We hypothesize that modulation of cAMP levels by butyrate is accomplished by FFAR2 activation, regulating NHE activity for pHi homoeostasis at least in part.


Fatty Acids, Volatile/metabolism , Receptors, G-Protein-Coupled/metabolism , Rumen/physiology , Sheep/physiology , Animals , Butyrates/pharmacology , Colforsin/pharmacology , Cyclic AMP/metabolism , Epithelium/metabolism , Female , Gastric Mucosa/metabolism , Hydrogen-Ion Concentration , Male , Monocarboxylic Acid Transporters/genetics , Monocarboxylic Acid Transporters/metabolism , Niacin/pharmacology , Protein Transport , Serous Membrane/metabolism
10.
Surg Endosc ; 34(11): 4818-4827, 2020 11.
Article En | MEDLINE | ID: mdl-31741157

BACKGROUND: Fluorescence-based enhanced reality (FLER) enables the quantification of fluorescence signal dynamics, which can be superimposed onto real-time laparoscopic images by using a virtual perfusion cartogram. The current practice of perfusion assessment relies on visualizing the bowel serosa. The aim of this experimental study was to quantify potential differences in mucosal and serosal perfusion levels in an ischemic colon segment. METHODS: An ischemic colon segment was created in 12 pigs. Simultaneous quantitative mucosal and serosal fluorescence imaging was obtained via intravenous indocyanine green injection (0.2 mg/kg), using two near-infrared camera systems, and computer-assisted FLER analysis. Lactate levels were measured in capillary blood of the colonic wall at seven regions of interest (ROIs) as determined with FLER perfusion cartography: the ischemic zone (I), the proximal and distal vascularized areas (PV, DV), and the 50% perfusion threshold proximally and distally at the mucosal and serosal side (P50M, P50S, D50M, D50S). RESULTS: The mean ischemic zone as measured (mm) for the mucosal side was significantly larger than the serosal one (56.3 ± 21.3 vs. 40.8 ± 14.9, p = 0.001) with significantly lower lactate values at the mucosal ROIs. There was a significant weak inverse correlation between lactate and slope values for the defined ROIs (r = - 0.2452, p = 0.0246). CONCLUSIONS: Mucosal ischemic zones were larger than serosal zones. These results suggest that an assessment of bowel perfusion from the serosal side only can underestimate the extent of ischemia. Further studies are required to predict the optimal resection margin and anastomotic site.


Capillaries , Colitis, Ischemic , Colon , Diagnosis, Computer-Assisted , Laparoscopy , Serous Membrane , Animals , Male , Capillaries/diagnostic imaging , Capillaries/physiopathology , Colitis, Ischemic/diagnosis , Colon/blood supply , Colon/diagnostic imaging , Diagnosis, Computer-Assisted/methods , Disease Models, Animal , Laparoscopy/methods , Serous Membrane/metabolism , Swine
11.
Front Immunol ; 10: 1115, 2019.
Article En | MEDLINE | ID: mdl-31156652

Tissue-resident memory T (Trm) cells are enriched at the sites of previous infection and required for enhanced protective immunity. However, the emergence of Trm cells and their roles in providing protection are unclear in the field of Helicobacter pylori (H. pylori) vaccinology. Here, our results suggest that conventional vaccine strategies are unable to establish a measurable antigen (Ag)-specific memory cell pool in stomach; in comparison, gastric subserous injection of mice with micro-dose of Alum-based H. pylori vaccine can induce a pool of local CD4+ Trm cells. Regional recruitment of Ag-specific CD4+ T cells depends on the engagement of Ag and adjuvant-induced inflammation. Prior subcutaneous vaccination enhanced this recruitment. A stable pool of Ag-specific CD4+ T cells can be detected for 240 days. Two weeks of FTY720 administration in immune mice suggests that these cells do not experience the recirculation. Immunohistochemistry results show that close to the vaccination site, abundant CD4+T cells locate on epithelial niches, independent of lymphocyte cluster. Paradigmatically, Ag-specific CD4+ T cells with a phenotype of CD69+CD103- are preferential on lymphocytes isolated from epithelium. Upon Helicobacter infection, CD4+ Trm cells orchestrate a swift recall response with the recruitment of circulating antigen-specific Th1/Th17 cells to trigger a tissue-wide pathogen clearance. This study investigates the vaccine-induced gastric CD4+ Trm cells in a mice model, and highlights the need for designing a vaccine strategy against H. pylori by establishing the protective CD4+ Trm cells.


Bacterial Vaccines/immunology , CD4-Positive T-Lymphocytes/immunology , Helicobacter Infections/immunology , Helicobacter pylori/immunology , T-Lymphocytes, Regulatory/physiology , Alum Compounds , Animals , Disease Resistance , Female , Humans , Immunologic Memory , Lymphocyte Activation , Mice , Serous Membrane/metabolism , Vaccination
12.
Pathol Oncol Res ; 25(3): 1143-1152, 2019 Jul.
Article En | MEDLINE | ID: mdl-30478720

All too often, conventional immunocytochemistry (ICC) via an antibody on cytological samples is limited to a few smears due to scant cellularity. To circumvent these limitations, this study employed a cell-type-specific aptamer as the core tool in ICC protocols for a timely and highly specific ICC diagnosis. S6, an aptamer against A549 lung carcinoma cells, was adopted instead of antibodies in this study for differentiating cancer cells in serosal fluids. Here, we developed three different strategies for discriminating the adenocarcinoma cells in effusion cytology specimens using the S6 aptamer in ICC. These strategies included a biotin-labeled S6 aptamer, an FAM-labeled S6 aptamer, and an activatable S6 aptamer. A total of 112 serosal fluid specimens with known diagnoses were evaluated by all three modes of use of the S6 aptamer. ICC procedures based on biotin-labeled or FAM-labeled S6 aptamers required time-consuming washing to avoid interference from nonspecific adsorption. ICC procedures based on an activatable S6 aptamer probe showed a weak fluorescence signal in the absence of target cells, but the procedures showed a strong fluorescence signal due to alteration of the conformation without any complicated washing steps, in the presence of targets. The specificity and sensitivity are higher in all three different ICC protocols based on the S6 aptamer than those for antibody protocols for differentiating adenocarcinoma cells in clinical effusion cytology. ICC based on cell-type-specific aptamers, instead of on a panel of a set of antibodies, is promising as an auxiliary method for the diagnosis of cancer.


Adenocarcinoma of Lung/diagnosis , Aptamers, Nucleotide/chemistry , Ascitic Fluid/metabolism , Fluorescence , Immunohistochemistry/methods , Lung Neoplasms/diagnosis , Serous Membrane/metabolism , A549 Cells , Adenocarcinoma of Lung/metabolism , Biosensing Techniques , Cytodiagnosis , Humans , Lung Neoplasms/metabolism
13.
J Pediatr Surg ; 53(12): 2435-2439, 2018 Dec.
Article En | MEDLINE | ID: mdl-30243737

BACKGROUND: Stem cell transplantation is a potential therapy for enteric neuropathies, including Hirschsprung disease. Proof-of-principle has been obtained using focal transplants into neonatal mouse colon. The challenge now is to deliver stem cells to a large surface area to reconstruct an enteric nerve plexus. One proposed method is serosal application using a polymer membrane. However, transserosal migration of stem cells has not been demonstrated in mature colon. This study aimed to develop an avian model to demonstrate stem cell migration across the intact serosa of mature colon. METHODS: Hindguts were obtained from E14 quail embryos, transplanted onto E8 chicken chorioallantoic membranes and harvested after 2 and 8 days. Tissues were assessed immunohistologically for apoptosis (caspase-3), maturity (α-SMA), preservation of mucosa (E-cadherin), and preservation of serosa (cytokeratin). RESULTS: Transient necrosis of the central mucosa was observed over the first two days, followed by recovery. Twenty-three grafts were assessed immunohistologically at day 8. Nineteen grafts demonstrated progressive maturation and an intact mucosa. Circumferential serosal preservation was observed in 9 grafts. No apoptosis was seen. CONCLUSION: Avian colon may be successfully harvested with an intact serosa. Large chorioallantoic membrane grafts remain viable for at least 8 days, and the serosa can be preserved throughout. This provides an economical platform for assessing transserosal migration of stem cells in mature colon.


Cell Movement/physiology , Colon/metabolism , Enteric Nervous System/cytology , Neural Stem Cells/metabolism , Serous Membrane/metabolism , Animals , Cadherins/metabolism , Caspase 3/metabolism , Colon/transplantation , Fluorescent Antibody Technique , Keratins/metabolism , Serous Membrane/cytology , Stem Cell Transplantation/methods
14.
Med Sci Monit ; 24: 4262-4270, 2018 Jun 21.
Article En | MEDLINE | ID: mdl-29926841

BACKGROUND The POZ/BTB and AT-hook-containing Zinc finger protein 1 (PATZ1) is a ubiquitously expressed transcription factor belonging to the POZ domain Krüppel-like zinc finger (POK) family. It is involved in the pathogenesis of a growing list of human diseases, including cancer. The effect of PATZ1 on serous ovarian carcinoma (SOC) remains unclear. This study initially explored the clinical significance of PATZ1 in patients with SOC, the relationship between its expression and the prognosis of SOC patients, and its role in tumor proliferation and invasion. MATERIAL AND METHODS Immunohistochemistry and quantitative real-time polymerase chain reaction (qPCR) were performed to characterize the expression of PATZ1 in SOC tissues. The relationship between PATZ1 expression and the clinicopathological features of patients with SOC was analyzed by chi-square test. Kaplan-Meier method and Cox regression analyses were utilized to evaluate the prognosis of SOC. PATZ1-constructed transfection-mediated overexpression was conducted. The CCK-8 assay was performed to examine the proliferation, while Transwell assay was used to detect the invasive capability. RESULTS The results of IHC and qPCR analyses showed that the expression of PATZ1 in cancerous tissue was significantly lower than that in non-cancerous tissues. Meanwhile, PATZ1 expression was significantly associated with tumor differentiation and LN metastasis. Survival analysis showed that PATZ1 expression was one of the independent prognosis factors for overall survival of SOC patients. In addition, overexpression of PATZ1 inhibited the proliferation and invasion of OVCAR3 cells by in vitro experiments. CONCLUSIONS Our data suggest that PATZ1 is a novel prognostic marker in SOC.


Kruppel-Like Transcription Factors/metabolism , Neoplasms, Glandular and Epithelial/metabolism , Ovarian Neoplasms/metabolism , Repressor Proteins/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Ovarian Epithelial , Cell Differentiation/physiology , Cell Line, Tumor , Disease Progression , Female , Humans , Kruppel-Like Transcription Factors/genetics , Lymphatic Metastasis , Middle Aged , Neoplasm Metastasis , Neoplasms, Glandular and Epithelial/genetics , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Prognosis , Repressor Proteins/genetics , Retrospective Studies , Serous Membrane/metabolism , Serous Membrane/pathology
15.
Sci Rep ; 7(1): 5918, 2017 07 19.
Article En | MEDLINE | ID: mdl-28724995

Formyl peptide receptors (FPRs) are G protein-coupled chemoattractant receptors expressed mainly in phagocytic leukocytes. High expression of FPRs has also been detected in several cancers but the functions of FPR1 in tumor invasion and metastasis is poorly understood. In this study, we investigated the expression of FPRs in primary human colorectal cancer (CRC) and analyzed the association of FPRs expression with clinicopathological parameters. The levels of FPRs mRNA, especially those of FPR1, were significantly higher in colorectal tumors than in distant normal tissues and adjacent non-tumor tissues. FPR1 mRNA expression was also associated with tumor serosal infiltration. FPR1 protein expression was both in the colorectal epitheliums and tumor infiltrating neutrophils/macrophages. Furthermore, the functions of FPR1 in tumor invasion and tissue repair were investigated using the CRC cell lines SW480 and HT29. Higher cell surface expression of FPR1 is associated with significantly increased migration in SW480 cells compared with HT29 cells that have less FPR1 membrane expression. Finally, genetic deletion of fpr1 increased the survival rate of the resulting knockout mice compared with wild type littermates in a mouse model of colitis-associated colorectal cancer. Our data demonstrate that FPR1 may play an important role in tumor cell invasion in CRC patients.


Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Receptors, Formyl Peptide/metabolism , Adult , Aged , Animals , Cell Line, Tumor , Cell Movement/genetics , Epithelium/metabolism , Epithelium/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Macrophages/pathology , Male , Mice, Inbred C57BL , Middle Aged , Neoplasm Invasiveness , Neutrophils/pathology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Formyl Peptide/genetics , Serous Membrane/metabolism , Serous Membrane/pathology , Xenograft Model Antitumor Assays
16.
Proc Natl Acad Sci U S A ; 114(31): 8157-8162, 2017 08 01.
Article En | MEDLINE | ID: mdl-28716911

Oscillatory morphodynamics provides necessary mechanical cues for many multicellular processes. Owing to their collective nature, these processes require robustly coordinated dynamics of individual cells, which are often separated too distantly to communicate with each other through biomaterial transportation. Although it is known that the mechanical balance generally plays a significant role in the systems' morphologies, it remains elusive whether and how the mechanical components may contribute to the systems' collective morphodynamics. Here, we study the collective oscillations in the Drosophila amnioserosa tissue to elucidate the regulatory roles of the mechanical components. We identify that the tensile stress is the key activator that switches the collective oscillations on and off. This regulatory role is shown analytically using the Hopf bifurcation theory. We find that the physical properties of the tissue boundary are directly responsible for synchronizing the oscillatory intensity and polarity of all inner cells and for orchestrating the spatial oscillation patterns inthe tissue.


Drosophila/embryology , Embryo, Nonmammalian/cytology , Models, Biological , Animals , Biomechanical Phenomena , Embryo, Nonmammalian/metabolism , Feedback, Physiological , Serous Membrane/cytology , Serous Membrane/metabolism , Tensile Strength
17.
Biomed Res ; 37(5): 299-304, 2016.
Article En | MEDLINE | ID: mdl-27784873

Overactive bladder is one of the major health problem especially in elderly people. Adenosine triphosphate (ATP) is released from urinary bladder cells and acts as a smooth muscle contraction and sensory signal in micturition but little is known about the role of ATP release in the pathophysiology of overactive bladder. To assess the relationship between ATP and overactive bladder, we used a partial bladder outlet obstruction (pBOO) model in rats. The bladder caused several changes by pBOO: An increase in bladder weight, hypertrophy of sub-urothelium and sub-serosal area, and frequent non-voiding bladder contraction during urine storage. Basal ATP release from urothelium and serosa of pBOO rats was significantly higher than that of normal rats. Distentioninduced ATP release from urothelium of normal and pBOO rats had no significant change. However, distention-induced ATP release from serosa of pBOO rats was higher than that of normal. These findings may identify ATP especially released from serosa as one of causes of non-voiding contractions and overactive bladder symptoms.


Adenosine Triphosphate/metabolism , Serous Membrane/metabolism , Urinary Bladder Neck Obstruction/metabolism , Urothelium/metabolism , Animals , Disease Models, Animal , Female , Rats , Serous Membrane/pathology , Urinary Bladder Neck Obstruction/pathology , Urinary Bladder Neck Obstruction/physiopathology , Urothelium/pathology
18.
J Surg Res ; 204(1): 39-46, 2016 07.
Article En | MEDLINE | ID: mdl-27451866

BACKGROUND: Ischemic injury of an organ causes metabolic change from aerobic to anaerobic metabolism. It has been shown in experimental studies on the heart and liver that such conversion may be detected by conventional microdialysis probes placed intra-parenchymatously, as well as on organ surfaces, by assaying lactate, pyruvate, glucose, and glycerol in dialysate. We developed a microdialysis probe (S-µD) intended for use solely on organ surfaces. The aim of this study was to assess whether the newly developed S-µD probe could be used for detection and monitoring of small bowel ischemia. METHODS: In anesthetized normoventilated pigs, a control S-µD probe was applied on the jejunal serosa 50 cm downstream from the duodenojejunal junction (DJJ). Starting 100 cm from DJJ, a 100-cm long ischemic segment was created by division of all mesenteric vessels. S-µDs were applied at 2.5, 5, 20, and 50 cm from the starting point of ischemia by serosal sutures. A standard µD probe was placed in the abdominal cavity as a further control. Dialysate was harvested before inducing ischemia and subsequently every 20 min for 4 h. Central venous blood was drawn every hour to monitor systemic lactate, C-reactive protein, and white blood cell count. RESULTS: Microdialysis lactate levels were significantly higher than baseline from 20 min on into protocol time in the ischemic segment and in the control S-µD probe. The peritoneal cavity probe showed no significant elevation. Lactate levels from the ischemic segment reached a plateau at 60 min. Courses of pyruvate, glucose, and glycerol levels were in accordance with transition from an aerobic to anaerobic metabolism in the bowel wall. No statistically significant changes in hemoglobin, white blood cell count, or lactate values in central venous blood were recorded. CONCLUSIONS: Assaying the aforementioned compounds in dialysate, harvested by the newly developed S-µD probe, allowed detection and monitoring of small bowel ischemia from 20 min on following its onset.


Ischemia/diagnosis , Jejunum/blood supply , Microdialysis/instrumentation , Serous Membrane/blood supply , Animals , Biomarkers/metabolism , Ischemia/metabolism , Ischemia/pathology , Jejunum/metabolism , Jejunum/pathology , Microdialysis/methods , Serous Membrane/metabolism , Serous Membrane/pathology , Swine
19.
Curr Opin Insect Sci ; 13: 86-92, 2016 02.
Article En | MEDLINE | ID: mdl-27436557

Morphogenetic functions of the amnioserosa, the serosa, the amnion, and the yolk sac are reviewed on the basis of recent studies in flies (Drosophila, Megaselia), beetles (Tribolium), and hemipteran bugs (Oncopeltus). Three hypotheses are presented. First, it is suggested that the amnioserosa of Drosophila and the dorsal amnion of other fly species function in a similar manner. Second, it is proposed that in many species with an amniotic cavity, the amnion determines the site of serosa rupture, which, through interactions between the serosa and the amnion, enables the embryo to break free from the amniotic cavity and to close its backside. Finally, it is concluded that the yolk sac is likely an important player in insect morphogenesis.


Insecta/embryology , Morphogenesis/physiology , Amnion/metabolism , Animals , Embryo, Nonmammalian , Extraembryonic Membranes/metabolism , Insecta/anatomy & histology , Serous Membrane/metabolism , Yolk Sac/metabolism
20.
J Basic Clin Physiol Pharmacol ; 27(4): 357-61, 2016 Jun 01.
Article En | MEDLINE | ID: mdl-26974137

BACKGROUND: The ability to absorb substances from the external environment is one of the features that make animals different from inanimate objects. In mammalian species, this quality is mainly the role of the small intestine. The process of absorption mainly takes place in the small intestine. This study was carried out to investigate the rate of glucose absorption in the intestine of albino rats and the effect of calcium and ouabain on the rate of glucose absorption. METHODS: Albino rats weighing between 200 and 250 g were used for this experiment. Guts were isolated and cut to segments. Test solution was injected into each of the isolated segments, which were then assayed for glucose. RESULTS: The result revealed that the rate of glucose absorption in the intestine of albino rats were found to be 3.02×10-1 g/min at the mucosa-to-serosa surface and 3.00×10-1 g/min at the serosa-to-mucosa surface, indicating that glucose was absorbed at both surfaces and that the rate of glucose absorption was higher in the mucosa-to-serosa direction than in the opposite direction. The rate of intestinal glucose absorption at different regions of the intestine and the effect of varying concentrations of calcium on the rate of glucose absorption revealed that glucose absorption was highest at the duodenum and lowest at the ileum. CONCLUSIONS: Ouabain blocked the rate of absorption of glucose in the intestine of albino rats.


Duodenum/metabolism , Glucose/metabolism , Ileum/metabolism , Intestinal Absorption/physiology , Animals , Calcium/metabolism , Mucous Membrane/metabolism , Rats , Serous Membrane/metabolism
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