-
Sheng Li Xue Bao : [Acta Physiologica... Aug 2016Epicardium is one of the important components of the heart and plays a critical role in cardiogenesis. Moreover, further studies have shown that epicardium contributes... (Review)
Review
Epicardium is one of the important components of the heart and plays a critical role in cardiogenesis. Moreover, further studies have shown that epicardium contributes to post-injury heart regeneration. After heart injury, epicardium secretes various signaling factors, regulating the cardiomyocyte proliferation and neovascularization. In addition, epicardium differentiates into many kinds of cells which take part in the heart repair in response to heart damage. In this review, we summarize recent progress on epicardial function, related signaling pathways and the potential clinical application, and provide a reference for future studies in epicardium and heart regeneration.
Topics: Heart; Pericardium; Regeneration; Signal Transduction
PubMed: 27546512
DOI: No ID Found -
Digestive Diseases (Basel, Switzerland) 2017Farnesoid X receptor (FXR) regulates the synthesis, transport and enterohepatic circulation of bile acids (BA) by modulating the expression of related genes in the liver... (Review)
Review
Farnesoid X receptor (FXR) regulates the synthesis, transport and enterohepatic circulation of bile acids (BA) by modulating the expression of related genes in the liver and small intestine. The composition of the gut microbiota is correlated with metabolic diseases, notably obesity and non-alcoholic fatty acid disease (NAFLD). Recent studies revealed that bacterial metabolism of BA can modulate FXR signaling in the intestine by altering the composition and concentrations of FXR agonist and antagonist. FXR agonist enhances while FXR antagonist suppresses obesity, NAFLD and insulin resistance. The role of intestinal FXR in metabolic disease was firmly established by the analysis of mice lacking FXR that are metabolic resistant to HFD-induced metabolic disease. This is mediated by FXR modulating in part the expression of genes involved in ceramide synthesis in the small intestine. In ileum of obese mice due to the presence of endogenous FXR agonists produced in the liver, these genes are activated, while in mice with altered levels of specific gut bacteria, levels of an FXR antagonist, tauro-β-muricholic acid (T-β-MCA) increase and FXR signaling and ceramide synthesis are repressed. T-β-MCA, which is metabolized in wild-type mice, led to the discovery of glycine-β-muricholic acid (Gly-MCA) that is stable in the intestine and a potent inhibitor of FXR signaling. These studies reveal that ceramides produced in the ileum under the control of FXR, influence metabolic disease, and suggest that novel FXR antagonist such as Gly-MCA that specifically inhibit intestine FXR, could serve as potential drug for the treatment of metabolic disease.
Topics: Animals; Bacteria; Humans; Intestinal Mucosa; Metabolic Diseases; Molecular Targeted Therapy; Receptors, Cytoplasmic and Nuclear; Signal Transduction
PubMed: 28249275
DOI: 10.1159/000450908 -
Revista Espanola de Enfermedades... Dec 2022Amyloidosis is a disease caused by extracellular deposition of abnormally folded proteins. While gastrointestinal involvement is relatively frequent in its systemic...
Amyloidosis is a disease caused by extracellular deposition of abnormally folded proteins. While gastrointestinal involvement is relatively frequent in its systemic form, isolated gastrointestinal disease is rare. We present the case of a 62-year-old man assessed for iron deficiency anemia and abdominal pain after starting antiplatelet therapy with acetylsalicylic acid and ticagrelor for ischemic heart disease. An esophagogastroduodenoscopy was performed as part of the study, showing thickened folds with pseudopolypoid morphology and nodular mucosa with a preserved crypt pattern in the duodenal bulb and second duodenal portion.
Topics: Male; Humans; Middle Aged; Duodenum; Amyloidosis; Gastrointestinal Diseases; Intestinal Mucosa; Anemia, Iron-Deficiency
PubMed: 35638766
DOI: 10.17235/reed.2022.8934/2022 -
Ophthalmology Feb 2018Despite posterior vitreous detachment being a common ocular event affecting most individuals in an aging population, there is little consensus regarding its precise...
PURPOSE
Despite posterior vitreous detachment being a common ocular event affecting most individuals in an aging population, there is little consensus regarding its precise anatomic definition. We investigated the morphologic appearance and molecular composition of the posterior hyaloid membrane to determine whether the structure clinically observed enveloping the posterior vitreous surface after posterior vitreous detachment is a true basement membrane and to postulate its origin. Understanding the relationship between the vitreous (in both its attached and detached state) and the internal limiting membrane of the retina is essential to understanding the cause of rhegmatogenous retinal detachment and vitreoretinal interface disorders, as well as potential future prophylactic and treatment strategies.
DESIGN
Clinicohistologic correlation study.
PARTICIPANTS
Thirty-six human donor globes.
METHODS
Vitreous bodies identified to have posterior vitreous detachment were examined with phase-contrast microscopy and confocal microscopy after immunohistochemically staining for collagen IV basement membrane markers, in addition to extracellular proteins that characterize the vitreoretinal junction (fibronectin, laminin) and vitreous gel (opticin) markers. The posterior retina similarly was stained to evaluate the internal limiting membrane. Findings were correlated to the clinical appearance of the posterior hyaloid membrane observed during slit-lamp biomicroscopy after posterior vitreous detachment and compared with previously published studies.
MAIN OUTCOME MEASURES
Morphologic appearance and molecular composition of the posterior hyaloid membrane.
RESULTS
Phase-contrast microscopy consistently identified a creased and distinct glassy membranous sheet enveloping the posterior vitreous surface, correlating closely with the posterior hyaloid membrane observed during slit-lamp biomicroscopy in patients with posterior vitreous detachment. Immunofluorescent confocal micrographs demonstrated the enveloping membranous structure identified on phase-contrast microscopy to show positive stain results for type IV collagen. Immunofluorescence of the residual intact internal limiting membrane on the retinal surface also showed positive stain results for type IV collagen.
CONCLUSIONS
The results of this study provide immunohistochemical evidence that the posterior hyaloid membrane is a true basement membrane enveloping the posterior hyaloid surface. Because this membranous structure is observed only after posterior vitreous detachment, the results of this study indicate that it forms part of the internal limiting membrane when the vitreous is in its attached state.
Topics: Adult; Aged; Aged, 80 and over; Basement Membrane; Collagen; Female; Humans; Imaging, Three-Dimensional; Immunohistochemistry; Male; Microscopy, Acoustic; Microscopy, Confocal; Middle Aged; Prospective Studies; Vitrectomy; Vitreous Body; Vitreous Detachment
PubMed: 28867131
DOI: 10.1016/j.ophtha.2017.08.001 -
Hearing Research Sep 2022Intra organ of Corti (OC) vibrations differ from those measured at the basilar membrane (BM), with higher amplitudes and a wide-band nonlinearity extending well below a...
Intra organ of Corti (OC) vibrations differ from those measured at the basilar membrane (BM), with higher amplitudes and a wide-band nonlinearity extending well below a region's best frequency. The vibrations are boosted by the cochlear amplifier, the active processes within the mammalian hearing organ, and are thus sensitive to metabolic or pharmacological manipulation. We introduced salicylate, a known blocker of outer hair cell (OHC) based electromotility, into the perilymphatic space by applying sodium salicylate onto the round window membrane. Vibration patterns of an area of the OC were mapped with phase sensitive optical coherence tomography before and after treatment; distortion product otoacoustic emissions (DPOAEs) were measured at similar times to assess the cochlear condition. Following treatment, all regions showed a loss of vibration amplitude and tuning while OHC-region vibrations retained their wide-band nonlinearity. OC vibrations, which had been relatively confined in a region including OHCs and extending to the BM at the outer pillar foot, became less confined with structures lateral to the OHCs sometimes exhibiting the highest amplitudes. Vibrations and DPOAEs could recover to baseline levels over approximately three hours post treatment. This article is part of the Special Issue Outer hair cell Edited by Joseph Santos-Sacchi and Kumar Navaratnam.
Topics: Animals; Basilar Membrane; Cochlea; Hair Cells, Auditory, Outer; Mammals; Organ of Corti; Salicylates; Vibration
PubMed: 34774368
DOI: 10.1016/j.heares.2021.108389 -
Wiley Interdisciplinary Reviews.... Jul 2018Efficient absorption of nutrients by the intestine is essential for life. In mammals and birds, convolution of the intestinal surface into finger-like projections called... (Review)
Review
Efficient absorption of nutrients by the intestine is essential for life. In mammals and birds, convolution of the intestinal surface into finger-like projections called villi is an important adaptation that ensures the massive surface area for nutrient contact that is required to meet metabolic demands. Each villus projection serves as a functional absorptive unit: it is covered by a simple columnar epithelium that is derived from endoderm and contains a mesodermally derived core with supporting vasculature, lacteals, enteric nerves, smooth muscle, fibroblasts, myofibroblasts, and immune cells. In cross section, the consistency of structure in the billions of individual villi of the adult intestine is strikingly beautiful. Villi are generated in fetal life, and work over several decades has revealed that villus morphogenesis requires substantial "crosstalk" between the endodermal and mesodermal tissue components, with soluble signals, cell-cell contacts, and mechanical forces providing specific dialects for sequential conversations that orchestrate villus assembly. A key part of this process is the formation of subepithelial mesenchymal cell clusters that act as signaling hubs, directing overlying epithelial cells to cease proliferation, thereby driving villus emergence and simultaneously determining the location of future stem cell compartments. Interestingly, distinct species-specific differences govern how and when tissue-shaping signals and forces generate mesenchymal clusters and control villus emergence. As the details of villus development become increasingly clear, the emerging picture highlights a sophisticated local self-assembled cascade that underlies the reproducible elaboration of a regularly patterned field of absorptive villus units. This article is categorized under: Vertebrate Organogenesis > From a Tubular Primordium: Non-Branched Comparative Development and Evolution > Organ System Comparisons Between Species Early Embryonic Development > Development to the Basic Body Plan.
Topics: Animals; Epithelial Cells; Humans; Intestinal Mucosa; Mice; Microvilli; Organogenesis; Rats; Signal Transduction; Species Specificity
PubMed: 29513926
DOI: 10.1002/wdev.317 -
Philosophical Transactions of the Royal... Dec 2022During the early development of Placentalia, a distinctive projection emerges at the posterior embryonic-extraembryonic interface of the conceptus; its fingerlike shape... (Review)
Review
During the early development of Placentalia, a distinctive projection emerges at the posterior embryonic-extraembryonic interface of the conceptus; its fingerlike shape presages maturation into the placental umbilical cord, whose major role is to shuttle fetal blood to and from the chorion for exchange with the mother during pregnancy. Until recently, the biology of the cord's vital vascular anlage, called the body stalk/allantois in humans and simply the allantois in rodents, has been largely unknown. Here, new insights into the development of the mouse allantois are featured, from its origin and mechanism of arterial patterning through its union with the chorion. Key to generating the allantois and its critical functions are the primitive streak and visceral endoderm, which together are sufficient to create the entire fetal-placental connection. Their newly discovered roles at the embryonic-extraembryonic interface challenge conventional wisdom, including the physical limits of the primitive streak, its function as sole purveyor of mesoderm in the mouse, potency of visceral endoderm, and the putative role of the allantois in the germ line. With this working model of allantois development, understanding a plethora of hitherto poorly understood orphan diseases in humans is now within reach. This article is part of the theme issue 'Extraembryonic tissues: exploring concepts, definitions and functions across the animal kingdom'.
Topics: Allantois; Animals; Embryo, Mammalian; Female; Humans; Mesoderm; Mice; Placenta; Pregnancy; Primitive Streak
PubMed: 36252214
DOI: 10.1098/rstb.2021.0251 -
Nature Reviews. Gastroenterology &... Jan 2021The intestinal epithelium serves the unique and critical function of harvesting dietary nutrients, while simultaneously acting as a cellular barrier separating tissues... (Review)
Review
The intestinal epithelium serves the unique and critical function of harvesting dietary nutrients, while simultaneously acting as a cellular barrier separating tissues from the luminal environment and gut microbial ecosystem. Two salient features of the intestinal epithelium enable it to perform these complex functions. First, cells within the intestinal epithelium achieve a wide range of specialized identities, including different cell types and distinct anterior-posterior patterning along the intestine. Second, intestinal epithelial cells are sensitive and responsive to the dynamic milieu of dietary nutrients, xenobiotics and microorganisms encountered in the intestinal luminal environment. These diverse identities and responsiveness of intestinal epithelial cells are achieved in part through the differential transcription of genes encoded in their shared genome. Here, we review insights from mice and other vertebrate models into the transcriptional regulatory mechanisms underlying intestinal epithelial identity and microbial responsiveness, including DNA methylation, chromatin accessibility, histone modifications and transcription factors. These studies are revealing that most transcription factors involved in intestinal epithelial identity also respond to changes in the microbiota, raising both opportunities and challenges to discern the underlying integrative transcriptional regulatory networks.
Topics: Animals; Cell Differentiation; Cellular Microenvironment; Gastrointestinal Microbiome; Gene Expression Regulation; Humans; Intestinal Mucosa; Intestines; Mice; Models, Animal; Nutrigenomics; Nutritional Physiological Phenomena; Transcription, Genetic; Zebrafish
PubMed: 33024279
DOI: 10.1038/s41575-020-00357-6 -
Nature Communications Nov 2022Stimulus transduction in cilia of olfactory sensory neurons is mediated by odorant receptors, Gαolf, adenylate cyclase-3, cyclic nucleotide-gated and chloride ion...
Stimulus transduction in cilia of olfactory sensory neurons is mediated by odorant receptors, Gαolf, adenylate cyclase-3, cyclic nucleotide-gated and chloride ion channels. Mechanisms regulating trafficking and localization of these proteins in the dendrite are unknown. By lectin/immunofluorescence staining and in vivo correlative light-electron microscopy (CLEM), we identify a retinitis pigmentosa-2 (RP2), ESCRT-0 and synaptophysin-containing multivesicular organelle that is not part of generic recycling/degradative/exosome pathways. The organelle's intraluminal vesicles contain the olfactory transduction proteins except for Golf subunits Gγ13 and Gβ1. Instead, Gβ1 colocalizes with RP2 on the organelle's outer membrane. The organelle accumulates in response to stimulus deprivation, while odor stimuli or adenylate cyclase activation cause outer membrane disintegration, release of intraluminal vesicles, and RP2/Gβ1 translocation to the base of olfactory cilia. Together, these findings reveal the existence of a dendritic organelle that mediates both stimulus-regulated storage of olfactory ciliary transduction proteins and membrane-delimited sorting important for G protein heterotrimerization.
Topics: Adenylyl Cyclases; Multivesicular Bodies; Olfactory Receptor Neurons; Receptors, Odorant; Smell; Cilia; Proteins; Olfactory Mucosa
PubMed: 36371422
DOI: 10.1038/s41467-022-34604-y -
The Journal of Experimental Medicine Mar 2023Group 2 innate lymphoid cells (ILC2) are functionally poised, tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. ILC2...
Group 2 innate lymphoid cells (ILC2) are functionally poised, tissue-resident lymphocytes that respond rapidly to damage and infection at mucosal barrier sites. ILC2 reside within complex microenvironments where they are subject to cues from both the diet and invading pathogens-including helminths. Emerging evidence suggests ILC2 are acutely sensitive not only to canonical activating signals but also perturbations in nutrient availability. In the context of helminth infection, we identify amino acid availability as a nutritional cue in regulating ILC2 responses. ILC2 are found to be uniquely preprimed to import amino acids via the large neutral amino acid transporters Slc7a5 and Slc7a8. Cell-intrinsic deletion of these transporters individually impaired ILC2 expansion, while concurrent loss of both transporters markedly impaired the proliferative and cytokine-producing capacity of ILC2. Mechanistically, amino acid uptake determined the magnitude of ILC2 responses in part via tuning of mTOR. These findings implicate essential amino acids as a metabolic requisite for optimal ILC2 responses within mucosal barrier tissues.
Topics: Immunity, Innate; Lymphocytes; Amino Acids; Cytokines; Mucous Membrane
PubMed: 36571761
DOI: 10.1084/jem.20221073