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Renewal of embryonic and neonatal-derived cardiac-resident macrophages in response to environmental cues abrogated their potential to promote cardiomyocyte proliferation via Jagged-1-Notch1

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Acta Pharmaceutica Sinica B 2023年第1期13卷 128-141页

作者： Rong Chen Shiqing Zhang Fang Liu Lin Xia Chong Wang Siamak Sandoghchian Shotorbani Huaxi Xu Subrata Chakrabarti Tianqing Peng Zhaoliang Su International Genome Center Jiangsu UniversityZhenjiang 212013China institute for Medical Immunology Jiangsu UniversityZhenjiang 212013China Department of Laboratory Medicine Affiliated Hospital of Jiangsu UniversityZhenjiang 212001China Department of Immunology Tabriz University of Medical SciencesTabriz ***Iran Lawson Health Research institute London Health Sciences CentreLondonOntario N6A 5w9Canada Department of Pathology and Laboratory Medicine Western UniversityLondonOntario N6A 5CICanada

Cardiac-resident macrophages(CRMs)play important roles in homeostasis,cardiac function,and *** CRMs play critical roles in cardiac regeneration of neonatal mice,their roles are yet to be fully ***,this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac *** mouse cardiac ontogeny,four CRM subsets exist successively:CX3CR1+CCR2-Ly6C-MHCII-(MP1),CX3CR1lowCCR2lowLy6C-MHCII-(MP2),CX3CR1-CCR2+Ly6C+MHCII-(MP3),and CX3CR1+CCR2-Ly6C-MHCII+(MP4).MP1 cluster has different derivations(yolk sac,fetal liver,and bone marrow)and multiple functions *** and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial ***2/3 subsets could survive throughout ***4,the main population in adult mouse hearts,contributed to *** ontogeny,MP1 can convert into MP4 triggered by changes in the cellular redox *** findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte *** findings also shed light on cardiac repair following injury.

关键词： Cardiac resident macrophages Cardiac regeneration Cardiac injury Cardiomyocyte proliferation Myocardial infarction

The integrative roles of chemokines at the maternal-feta interface in early pregnancy

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Cellular & Molecular Immunology 2014年第5期11卷 438-448页

作者： Mei-Rong Du Song-Cun Wang Da-Jin Li M-RD and S-CW contributed equally to this work. Laboratory for Reproductive Immunology Hospital and Institute of Obstetrics and Gynecology Fudan University Shanghai Medical College Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases Shanghai China

embryos express paternal antigens that are foreign to the mother, but the mother provides a special immune milieu at the fetal-maternal interface to permit rather than reject the embryo growth in the uterus until parturition by establishing precise crosstalk between the mother and the fetus. There are unanswered questions in the maintenance of pregnancy, including the poorly understood phenomenon of maternal tolerance to the allogeneic conceptus, and the remarkable biological roles of placental trophoblasts that invade the uterine wall. Chemokines are multifunctional molecules initially described as having a role in leukocyte trafficking and later found to participate in developmental processes such as differentiation and directed migration. It is increasingly evident that the gestational uterine microenvironment is characterized, at least in part, by the differential expression and secretion of chemokines that induce selective trafficking of leukocyte subsets to the maternal-fetal interface and regulate multiple events that are closely associated with normal pregnancy. Here, we review the expression and function of chemokines and their receptors at the maternal-fetal interface, with a special focus on chemokine as a key component in trophoblast invasiveness and placental angiogenesis, recruitment and instruction of immune cells so as to form a fetus-supporting milieu during pregnancy. The chemokine network is also involved in pregnancy complications.

关键词： chemokine decidua pregnancy pregnant complications trophoblast

Effect of Maternal Diabetes on Pre- and Post-Natal Redox Status of F1 Rat Offspring

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Open Journal of Endocrine and Metabolic diseases 2014年第5期4卷 111-127页

作者： Maher A. Kamel Madiha H. Helmy Mervat Y. Hanafi Shimaa A. Mahmoud Hanan Abo Elfetooh Department of Biochemistry Medical Research Institute University of Alexandria Alexandria Egypt

Background: The oxidative stress and disturbed redox signaling during gestation my play an important role in the fetal programming of adult diabetes. Objective: The study aimed to investigate the effects of maternal diabetes on pre- and post-natal pancreatic and peripheral tissues redox and oxidative status in order to clarify their role in the diabetogenic programming of F1 offspring. Methods: Two groups of female Wistar rats were used (diabetic and control);diabetes was neonatally induced by STZ injection to 5-day old rats. 10 pregnancies of each group were terminated at GD 17 to obtain placentas and fetal pancreas, liver, muscle and adipose tissues for prenatal measurements. The rest of pregnancies were completed to term and the offspring were weaned to control diet or high-caloric (HCD) diet and followed up for 30 weeks. Every 5 weeks 10 male rats were sacrificed and serum and tissues were obtained for assessment of fasting blood glucose, tissues content of 8-oxo-dG, TBARS, GSH, GSSG, antioxidant enzymes and caspase-3. Results: The results indicated that, prenatally redox status of the foetuses of diabetic mothers is shifted toward more oxidizing environment which results from elevated oxidative stress and impaired antioxidants as indicated by elevated fetal tissues content of 8-oxo-dG, TBARS and GSSG and decreased GSH and GSH/GSSG ratio. All of these induce the apoptotic pathway in fetal pancreas. Postnatally, impaired glucose tolerance in the offspring of diabetic mothers is detected at 15th week of age and no hyperglycemia was detected until age of 30 weeks in the offspring under CD while some of offspring under HCD at age 25 weeks and most of them at 30 weeks have developed hyperglycemia. The pancreas of the offspring of diabetic mothers suffers from oxidative stress from the 5th week of age as indicated by elevated levels of nuclear and mitochondrial 8-oxo-dG contents and TBARS. Also, GSH level showed depletion with age and the activity of glutathione reduc

关键词： fetal Origin of disease Diabetes GSH Redox 8-Oxo-dG Apoptosis Oxidative Stress

REGULATORY EFFECTS OF HUMAN RECOMBINANT IL-6 ON NATURAL KILLER CELL ACTIVITY OF HUMAN fetal SPLEENS

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Chinese Journal of Cancer Research 1991年第1期3卷 38-41页

作者：路力生崔正言田志刚 Department of Immunology Institute of Basic Medical Sciences Shandong Academy of Medical Sciences Jinan Shandong Cancer Biotherapy Centre Jinan

In the present study it was proved first that human recombinant interleukin-6(HrIL-6) significantly augmented natural killer(NK) cell activity derived from human fetal spleens against K562 target cells in a 4 hours 51Cr release assay. The enhancement of NK activity with 24 hours preincubation in HrlL-6 was dose-dependent, and significantly higher than that of fresh NK cells and controls cultured with RPMI-1640 medium alone (Pfetal spleens at 20 to 40 weeks of gestation (up to 2.24 to 2.78 times), and no difference of NK activity of fetal splenocytes treated by HrIL-6 was observed between different fetal age (32.3% to 45.4%, P>0.05). Furthermore, IL-6-augmented NK activity of fetal splenocytes was very similar to adult levels (P>0.05). These finding strongly indicated that IL-6 plays an important role in the development of NK cell function during the gestational period, suggesting that IL-6 may be of importance in the regulation of host defense mechanisms against malignancies and viral diseases.

关键词： IL REGULATORY EFFECTS OF HUMAN RECOMBINANT IL-6 ON NATURAL KILLER CELL ACTIVITY OF HUMAN fetal SPLEENS

New model for cardiomyocyte sheet transplantation using a virus-cell fusion technique

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World Journal of Stem Cells 2015年第5期7卷 883-893页

作者： Yuto Takahashi Daihachiro Tomotsune Sakiko Takizawa Fengming Yue Mika Nagai Tadayuki Yokoyama Kanji Hirashima Katsunori Sasaki Department of Histology and embryology Shinshu University School of Medicine institute for Biomedical Sciences Interdisciplinary Cluster for Cutting Edge Research Shinshu University Bourbon Corporation Kashiwazaki Niigata 945-8611 Japan

AIM: To facilitate close contacts between transplanted cardiomyocytes and host skeletal muscle using cell fusion mediated by hemagglutinating virus of Japan envelope(HVJ-E) and tissue maceration. METHODS: Cardiomyocytes(1.5 × 106) from fetal rats were first cultured. After proliferation, some cells were used for fusion with adult muscle fibers using HVJ-E. Other cells were used to create cardiomyocyte sheets(area: about 3.5 cm2 including 2.1 × 106 cells), which were then treated with Nile blue, separated, and transplanted between the latissimus dorsi and intercostal muscles of adult rats with four combinations of HVJ-E and/or Na OH maceration: G1: HVJ-E(+), Na OH(+), Cardiomyocytes(+); G2: HVJ-E(-), NaO H(+), Cardiomyocytes(+); G3: HVJ-E(+),Na OH(-), Cardiomyocytes(+); G4: HVJ-E(-), Na OH(-), Cardiomyocytes(-). At 1 and 2 wk after transplantation, the four groups were compared by detection of beating domains, motion images using moving target analysis software, action potentials, gene expression of MLC-2v and Mesp1 by reverse transcription-polymerase chain reaction, hematoxylin-eosin staining, and immunostaining for cardiac troponin and skeletal ***: In vitro cardiomyocytes were fused with skeletal muscle fibers using HVJ-E. Cardiomyocyte sheets remained in the primary transplanted sites for 2 wk. Although beating domains were detected in G1, G2, and G3 rats, G1 rats prevailed in the number, size, motion image amplitudes, and action potential compared with G2 and G3 rats. Close contacts were only found in G1 rats. At 1 wk after transplantation, the cardiomyocyte sheets showed adhesion at various points to the myoblast layer in the latissimus dorsi muscle. At 2 wk after transplantation, close contacts were seen over a broad area. Part of the skeletal muscle sarcoplasma seemed to project into the myocardiocyte plasma and some nuclei appeared to share both ***: The present results show that close contacts were acquired and facilitated the

关键词： Cardiomyocyte sheet Latissimus dorsi Hemagglutinating virus of Japan envelope Cell fusion NaOH Maceration Cellular transplantation method

Thrombospondin-1 Expression in RPE and Choroidal Neovascular Membranes

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眼科学报 2006年第4期22卷 265-274页

作者： Shikun He Francesca Incardona Manlin Ji Stephen J. Ryan David R. Hinton Departments of Patholog Keck School of Medicine of the University of Southern Cdifornia Ophthalmology Keck School of Medicine of the University of Southern Cdifornia Doheny Eye institute Los A ngeles CA

Purpose: To investigate the expression of thrombospondin 1 (TSP-1) in retinal pigment epithelium (RPE) and choroidal neovascular membranes (CNVMs) from patients with age-related macular degeneration (AMD). Methods: Tissue sections from normal human fetal and adult eyes and surgically removed CNVMs were immunostained for TSP-1 localization. Polymerase chain reaction and Western blotting were used to analyze TSP-1 mRNA and protein from human RPE cells, respectively. TSP-1 in the supernatant of cultured RPE cells and eye explants were measured using enzyme-linked immunosorbent assay. MTT assay was used to evaluate the RPE survival after TSP-1 treatment. Results: The strongest immunostaining for TSP-1 was observed in the RPE monolayer around drusen in early AMD. The intensity of TSP-1 staining in normal eye sections was much weaker than that of early AMD and CNVM. TSP-1 mRNA was positive in cultured fetal and adult RPE cells. There was increasing secretion of TSP-1 into the supernatant of cultured RPE and eye explants. The specific band of TSP-1 was identified by Western blot. No significant inhibition of RPE survival was found with the exposure to TSP-1. Conclusions: TSP-1 expression in drusen and CNVM was upregulated and associated with RPE monolayer. TSP-1 may be a natural negative regulator for choroidal neovascularization.

关键词： thrombospondin 1 retinal pigment epithelium choroidal neovascular membrane

Effects of low-oxygen conditions on embryo growth in the painted turtle,Chrysemys picta

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Integrative Zoology 2017年第2期12卷 148-156页

作者： Gerardo A.CORDERO Matthew L.KARNATZ Jon C.SVENDSEN Eric J.GANGLOFF Department of Ecology Evolutionand Organismal BiologyIowa State UniversityAmesIowaUSA Technical University of Denmark National Institute of Aquatic ResourcesFreshwater FisheriesSilkeborgDenmark Interdisciplinary Centre of Marine and Environmental Research University of PortoPortoPortugal

Low-oxygen conditions(hypoxia;<21%O_(2))are considered unfavorable for growth;yet,embryos of many vertebrate taxa develop successfully in hypoxic subterranean *** enhanced tolerance to hypoxia has been demonstrated in... 详细信息

Low-oxygen conditions(hypoxia;embryos of many vertebrate taxa develop successfully in hypoxic subterranean *** enhanced tolerance to hypoxia has been demonstrated in adult reptiles,such as in the painted turtle(Chrysemys picta),its effects on sensitive embryo life stages warrant *** tested the hypothesis that short-term hypoxia negatively affects growth during day 40 of development in ***,when O_(2) demands are highest in embryos.A brief,but severe,hypoxic event(5%O_(2) for 0.5 h)moderately affected embryo growth,causing a 13%reduction in mass(relative to a normoxic control).The same condition had no effect during day 27;instead,a nearly anoxic event(1%O_(2) for 72 h)caused a 5%mass *** embryos survived the egg incubation *** study supports the assumption that reptilian embryos are resilient to intermittently low O_(2) in subterranean *** work is needed to ascertain responses to suboptimal O_(2) levels while undergoing dynamic changes in developmental physiology.

关键词： embryo metabolism embryo respiration growth rate nest environment oxygen consumption rate

Developmental expression of Cyclin H and Cdk7 in zebrafish: the essential role of Cyclin H during early embryo development

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Cell Research 2007年第2期17卷 163-173页

作者： Qing Yun Liu~1 Zhi Li Wu~1 Wen Jian Lv~1 Yuan Chang Yan~(1,2) Yi Ping Li~1 ~1Lab of Molecular Cell Biology,institute of Biochemistry and Cell Biology,Shanghai institutes for Biological Science,Chinese Academy of Sciences,Graduate School of the Chinese Academy of Sciences,320 Yue Yang Road,Shanghai 200031,China ~2Model Organism Division,E-institutes of Shanghai University,Shanghai 200025,China Lab of Molecular Cell Biology Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Science Chinese Academy of Sciences Graduate School of the Chinese Academy of Sciences Shanghai China Model Organism Division E-institutes of Shanghai University Shanghai China

Cyclin-dependent kinase 7(Cdk7)is the catalytic subunit of the metazoan Cdk-activating kinase(CAK).Activationof Cdk7 requires its association with a regulatory subunit,Cyclin *** the Cdk7/Cyclin H complex has beenimplicated in the regulation of RNA polymerase in several species,the precise function of their orthologs in zebrafish hasnot been fully *** this study,we isolated from zebrafish blastula embryos two cDNAs encoding the orthologsof human Cyclin H and Cdk7,and examined the role of Cdk7/Cvclin H in zebrafish *** analysisshowed that the zebrafish Cyclin H and Cdk7 cDNAs encode proteins with 65% and 86% identity to the respective hu-man ***-PCR and whole-mount in situ hybridization analyses of their expression in unfertilized eggs,embryosand organs of adult fish suggested that Cyclin H and Cdk7 messages are maternally *** data also showed thattheir transcripts were detected throughout *** of Cyclin H transcripts was found to be ubiquitousduring early stages of development and become restricted to the anterior neural tube,brain,eyes,procreate tissues,liverand heart by 5 days *** of a dominant-negative form of Cyclin H delayed the onset of zygotictranscription in the early embryo,resulting in apoptosis at 5 hours post-fertilization and leading to sever defects in tis-sues normally exhibiting high levels of Cyclin H *** results implicate Cyclin H in the regulation of thetranscriptional machinery during midblastula transition and suggest that it is an essential gene in early zebrafish larvaldevelopment.

关键词： Zebrafish Cyclin H Cdk7 whole-mount in situ hybridization embryonic development midblasmla transition

Sexual dimorphism in the number of microglial cells isolated from neonate mice

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Precision Medicine Research 2021年第3期3卷 12-16页

作者： Maryam Khajeh-Mobarakeh Farshad Homayouni Moghadam Department of Biology ACECR Institute of Higher EducationIsfahanIran Department of animal Biotechnology Cell Science Research CenterRoyan Institute for BiotechnologyACECRIsfahanIran

Background:Microglia are brain resident macrophages originating from mesodermal/mesenchymal cells that migrate into the CNS as early as embryonic day 9 in mice(E9)prior to the emergence of neurons and other *** have variety of neuro-developmental and homeostatic functions during early embryonic central nervous system development and later in the adult *** may be responsible for mediating some gender-related structural and functional differences in the ***,identifying the microglia content and amount of migrated microglia in embryonic stage would be helpful to determine the function of microglia in induction of brain gender-related *** of its complexity to determine the exact number of microglia in embryo,and since most studies harvest microglia form neonate mice,but it is not completely determined yet if there is any difference in the content of microglia in male and female ***:Brains were extracted from male and female neonates to prepare mixed glia,then microglia were extracted from cultured mixed glia using shaking *** microglia were counted,cultured and gone under microscopic and flow cytometry ***:The number of microglia harvested from male and female pubs is different and presumably male pubs have more microglia ab *** assessments on presence of amoeboid,rod like and ramified types showed that both genders have similar ***:Presence of a greater number of ab initio microglia in male neonates could indicate that gender-difference in the number of microglia may play a role in gender-dependent brain development from infancy.

关键词： Microglia Gender Brain Sex Neonatal Mixed glia