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Cureus Sep 2023The aim of this literature review was to analyze all available scientific data on apical extrusion and to identify and associate the possible factors influencing the... (Review)
Review
The aim of this literature review was to analyze all available scientific data on apical extrusion and to identify and associate the possible factors influencing the occurrence of apical extrusion, ranging from the choice of the canal shaping system, the irrigation technique, to the choice of diameter and the apical limit of preparation. A bibliographic search for relevant articles on apical extrusion of debris, irrigants, and bacteria was performed using the following databases: PubMed, Cochrane Library, and ScienceDirect. This search identified articles published between 2010 and 2023 in two languages (French and English). After selective sorting, 25 relevant documents were included. All the studies retained clearly agree on the inherent nature of apical extrusion during endodontic treatment. At the same time, we also understand that the amount of extrusion can be influenced by a number of parameters throughout endodontic therapy. According to this review, despite the undeniable nature of apical extrusion during endodontic therapy, studies with relatable experimental models that approach in vivo conditions are required to establish exploitable conclusions regarding apical extrusion and its prevention.
PubMed: 37720124
DOI: 10.7759/cureus.45211 -
ELife Sep 2023The acquisition of distinct branch sizes and shapes is a central aspect in tubular organ morphogenesis and function. In the airway tree, the interplay of apical...
The acquisition of distinct branch sizes and shapes is a central aspect in tubular organ morphogenesis and function. In the airway tree, the interplay of apical extracellular matrix (ECM) components with the underlying membrane and cytoskeleton controls tube elongation, but the link between ECM composition with apical membrane morphogenesis and tube size regulation is elusive. Here, we characterized Emp (epithelial membrane protein), a CD36 homolog belonging to the scavenger receptor class B protein family. mutant embryos fail to internalize the luminal chitin deacetylases Serp and Verm at the final stages of airway maturation and die at hatching with liquid filled airways. Emp localizes in apical epithelial membranes and shows cargo selectivity for LDLr-domain containing proteins. mutants also display over elongated tracheal tubes with increased levels of the apical proteins Crb, DE-cad, and phosphorylated Src (p-Src). We show that Emp associates with and organizes the βH-Spectrin cytoskeleton and is itself confined by apical F-actin bundles. Overexpression or loss of its cargo protein Serp lead to abnormal apical accumulations of Emp and perturbations in p-Src levels. We propose that during morphogenesis, Emp senses and responds to luminal cargo levels by initiating apical membrane endocytosis along the longitudinal tube axis and thereby restricts airway elongation.
Topics: Animals; Drosophila melanogaster; Drosophila Proteins; Endocytosis; Morphogenesis; Receptors, Scavenger; Trachea
PubMed: 37706489
DOI: 10.7554/eLife.84974 -
Biomolecules Jul 2023Periradicular tissues have a rich supply of peripheral afferent neurons, also known as nociceptive neurons, originating from the trigeminal nerve. While their primary... (Review)
Review
Periradicular tissues have a rich supply of peripheral afferent neurons, also known as nociceptive neurons, originating from the trigeminal nerve. While their primary function is to relay pain signals to the brain, these are known to be involved in modulating innate and adaptive immunity by initiating neurogenic inflammation (NI). Studies have investigated neuroanatomy and measured the levels of biomolecules such as cytokines and neuropeptides in human saliva, gingival crevicular fluid, or blood/serum samples in apical periodontitis (AP) to validate the possible role of trigeminal nociceptors in inflammation and tissue regeneration. However, the contributions of nociceptors and the mechanisms involved in the neuro-immune interactions in AP are not fully understood. This narrative review addresses the complex biomolecular interactions of trigeminal nociceptors with macrophages, the effector cells of the innate immune system, in the clinical manifestations of AP.
Topics: Humans; Nociceptors; Inflammation; Periapical Periodontitis; Pain; Macrophages
PubMed: 37627258
DOI: 10.3390/biom13081193 -
Circulation Research Feb 2024Extracellular vesicles (EVs) contain bioactive cargo including miRNAs and proteins that are released by cells during cell-cell communication. Endothelial cells (ECs)...
BACKGROUND
Extracellular vesicles (EVs) contain bioactive cargo including miRNAs and proteins that are released by cells during cell-cell communication. Endothelial cells (ECs) form the innermost lining of all blood vessels, interfacing with cells in the circulation and vascular wall. It is unknown whether ECs release EVs capable of governing recipient cells within these 2 separate compartments. Given their boundary location, we propose ECs use bidirectional release of distinct EV cargo in quiescent (healthy) and activated (atheroprone) states to communicate with cells within the circulation and blood vessel wall.
METHODS
EVs were isolated from primary human aortic ECs (plate and transwell grown; ±IL [interleukin]-1β activation), quantified, visualized, and analyzed by miRNA transcriptomics and proteomics. Apical and basolateral EC-EV release was determined by miRNA transfer, total internal reflection fluorescence and electron microscopy. Vascular reprogramming (RNA sequencing) and functional assays were performed on primary human monocytes or smooth muscle cells±EC-EVs.
RESULTS
Activated ECs increased EV release, with miRNA and protein cargo related to atherosclerosis. EV-treated monocytes and smooth muscle cells revealed activated EC-EV altered pathways that were proinflammatory and atherogenic. ECs released more EVs apically, which increased with activation. Apical and basolateral EV cargo contained distinct transcriptomes and proteomes that were altered by EC activation. Notably, activated basolateral EC-EVs displayed greater changes in the EV secretome, with pathways specific to atherosclerosis. In silico analysis determined compartment-specific cargo released by the apical and basolateral surfaces of ECs can reprogram monocytes and smooth muscle cells, respectively, with functional assays and in vivo imaging supporting this concept.
CONCLUSIONS
Demonstrating that ECs are capable of polarized EV cargo loading and directional EV secretion reveals a novel paradigm for endothelial communication, which may ultimately enhance the design of endothelial-based therapeutics for cardiovascular diseases such as atherosclerosis where ECs are persistently activated.
Topics: Humans; Endothelial Cells; MicroRNAs; Extracellular Vesicles; Cell Communication; Atherosclerosis
PubMed: 38174557
DOI: 10.1161/CIRCRESAHA.123.322993 -
Clinical Research in Cardiology :... May 2024Since the first description of apical hypertrophic cardiomyopathy (ApHCM) in 1976, contrasting information from all over the world has emerged regarding the natural... (Review)
Review
Since the first description of apical hypertrophic cardiomyopathy (ApHCM) in 1976, contrasting information from all over the world has emerged regarding the natural history of the disease. However, the recommended guidelines on hypertrophic cardiomyopathy (HCM) pay a cursory reference to ApHCM, without ApHCM-specific recommendations to guide the diagnosis and management. In addition, cardiologists may not be aware of certain aspects that are specific to this disease subtype, and a robust understanding of specific disease features can facilitate recognition and timely diagnosis. Therefore, the review covers the incidence, pathogenesis, and characteristics of ApHCM and imaging methods. Echocardiography and cardiovascular magnetic resonance imaging (CMR) are the most commonly used imaging methods. Moreover, this review presents the management strategies of this heterogeneous clinical entity. In this review, we introduce a novel transapical beating-heart septal myectomy procedure for ApHCM patients with a promising short-time result.
Topics: Humans; Apical Hypertrophic Cardiomyopathy; Cardiomyopathy, Hypertrophic; Echocardiography
PubMed: 37982860
DOI: 10.1007/s00392-023-02328-8 -
The Journal of Cell Biology Dec 2023Although mutations in the SCRIB gene lead to multiple morphological organ defects in vertebrates, the molecular pathway linking SCRIB to organ shape anomalies remains...
Although mutations in the SCRIB gene lead to multiple morphological organ defects in vertebrates, the molecular pathway linking SCRIB to organ shape anomalies remains elusive. Here, we study the impact of SCRIB-targeted gene mutations during the formation of the gut epithelium in an organ-on-chip model. We show that SCRIB KO gut-like epithelia are flatter with reduced exposed surface area. Cell differentiation on filters further shows that SCRIB plays a critical role in the control of apical cell shape, as well as in the basoapical polarization of myosin light chain localization and activity. Finally, we show that SCRIB serves as a molecular scaffold for SHROOM2/4 and ROCK1 and identify an evolutionary conserved SHROOM binding site in the SCRIB carboxy-terminal that is required for SCRIB function in the control of apical cell shape. Our results demonstrate that SCRIB plays a key role in epithelial morphogenesis by controlling the epithelial apical contractility during cell differentiation.
Topics: Animals; Binding Sites; Biological Evolution; Cell Differentiation; Cell Shape; Epithelium; Microphysiological Systems; Membrane Proteins; Morphogenesis
PubMed: 37930352
DOI: 10.1083/jcb.202211113 -
BioRxiv : the Preprint Server For... Aug 2023The uterine epithelium is composed of a single layer of hormone responsive polarized epithelial cells that line the lumen and form tubular glands. Endometrial epithelial...
The uterine epithelium is composed of a single layer of hormone responsive polarized epithelial cells that line the lumen and form tubular glands. Endometrial epithelial organoids (EEO) can be generated from uterine epithelia and recapitulate cell composition and hormone responses . As such, the development of EEO represents a major advance for facilitating mechanistic studies . However, a major limitation for the use of EEO cultured in basement membrane extract and other hydrogels is the inner location of apical membrane, thereby hindering direct access to the apical surface of the epithelium to study interactions with the embryo or infectious agents such as viruses and bacteria. Here, a straightforward strategy was developed that successfully reverses the polarity of EEO. The result is an apical-out organoid that preserves a distinct apical-basolateral orientation and remains responsive to ovarian steroid hormones. Our investigations highlight the utility of polarity-reversed EEO to study interactions with and blastocysts. This method of generating apical-out EEO lays the foundation for developing new functional assays, particularly regarding epithelial interactions with embryos during pregnancy or other luminal constituents in a pathological or diseased state.
PubMed: 37645779
DOI: 10.1101/2023.08.18.553918 -
EMBO Reports Sep 2023Hepatocytes form bile canaliculi that dynamically respond to the signalling activity of bile acids and bile flow. Little is known about their responses to intraluminal...
Hepatocytes form bile canaliculi that dynamically respond to the signalling activity of bile acids and bile flow. Little is known about their responses to intraluminal pressure. During embryonic development, hepatocytes assemble apical bulkheads that increase the canalicular resistance to intraluminal pressure. Here, we investigate whether they also protect bile canaliculi against elevated pressure upon impaired bile flow in adult liver. Apical bulkheads accumulate upon bile flow obstruction in mouse models and patients with primary sclerosing cholangitis (PSC). Their loss under these conditions leads to abnormally dilated canaliculi, resembling liver cell rosettes described in other hepatic diseases. 3D reconstruction reveals that these structures are sections of cysts and tubes formed by hepatocytes. Mathematical modelling establishes that they positively correlate with canalicular pressure and occur in early PSC stages. Using primary hepatocytes and 3D organoids, we demonstrate that excessive canalicular pressure causes the loss of apical bulkheads and formation of rosettes. Our results suggest that apical bulkheads are a protective mechanism of hepatocytes against impaired bile flow, highlighting the role of canalicular pressure in liver diseases.
Topics: Mice; Animals; Bile; Liver; Bile Canaliculi; Liver Diseases; Hepatocytes
PubMed: 37522754
DOI: 10.15252/embr.202357181 -
The Journal of Cell Biology Sep 2023Apical constriction is a cell shape change that drives key morphogenetic events during development, including gastrulation and neural tube formation. The forces driving...
Apical constriction is a cell shape change that drives key morphogenetic events during development, including gastrulation and neural tube formation. The forces driving apical constriction are primarily generated through the contraction of apicolateral and/or medioapical actomyosin networks. In the Drosophila ventral furrow, the medioapical actomyosin network has a sarcomere-like architecture, with radially polarized actin filaments and centrally enriched non-muscle myosin II and myosin activating kinase. To determine if this is a broadly conserved actin architecture driving apical constriction, we examined actomyosin architecture during C. elegans gastrulation, in which two endodermal precursor cells internalize from the surface of the embryo. Quantification of protein localization showed that neither the non-muscle myosin II NMY-2 nor the myosin-activating kinase MRCK-1 is enriched at the center of the apex. Further, visualization of barbed- and pointed-end capping proteins revealed that actin filaments do not exhibit radial polarization at the apex. Our results demonstrate that C. elegans endodermal precursor cells apically constrict using a mixed-polarity actin filament network and with myosin and a myosin activator distributed throughout the network. Taken together with observations made in other organisms, our results demonstrate that diverse actomyosin architectures are used in animal cells to accomplish apical constriction.
Topics: Animals; Actin Cytoskeleton; Actomyosin; Caenorhabditis elegans; Constriction; Morphogenesis; Myosin Type II; Myosins; Caenorhabditis elegans Proteins
PubMed: 37351566
DOI: 10.1083/jcb.202302102 -
The Journal of Cell Biology Feb 2024Multiple physiology-pertinent transmembrane proteins reach the cell surface via the Golgi-bypassing unconventional protein secretion (UcPS) pathway. By employing C....
Multiple physiology-pertinent transmembrane proteins reach the cell surface via the Golgi-bypassing unconventional protein secretion (UcPS) pathway. By employing C. elegans-polarized intestine epithelia, we recently have revealed that the small GTPase RAB-8/Rab8 serves as an important player in the process. Nonetheless, its function and the relevant UcPS itinerary remain poorly understood. Here, we show that deregulated RAB-8 activity resulted in impaired apical UcPS, which increased sensitivity to infection and environmental stress. We also identified the SNARE VTI-1/Vti1a/b as a new RAB-8-interacting factor involved in the apical UcPS. Besides, RAB-11/Rab11 was capable of recruiting RABI-8/Rabin8 to reduce the guanine nucleotide exchange activity of SMGL-1/GEF toward RAB-8, indicating the necessity of a finely tuned RAB-8/RAB-11 network. Populations of RAB-8- and RAB-11-positive endosomal structures containing the apical UcPS cargo moved toward the apical side. In the absence of RAB-11 or its effectors, the cargo was retained in RAB-8- and RAB-11-positive endosomes, respectively, suggesting that these endosomes are utilized as intermediate carriers for the UcPS.
Topics: Animals; Caenorhabditis elegans; Cell Membrane; Protein Transport; Caenorhabditis elegans Proteins; rab GTP-Binding Proteins; Endosomes
PubMed: 38019180
DOI: 10.1083/jcb.202306107