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Plant Physiology Sep 2023An apical hook is a special structure formed during skotomorphogenesis in dicotyledonous plant species. It is critical for protecting the shoot apical meristem from...
An apical hook is a special structure formed during skotomorphogenesis in dicotyledonous plant species. It is critical for protecting the shoot apical meristem from mechanical damage during seed germination and hypocotyl elongation in soil. Brassinosteroid (BR) and jasmonate (JA) phytohormones antagonistically regulate apical hook formation. However, the interrelationship between BRs and JAs in this process has not been well elucidated. Here, we reveal that JAs repress BRs to regulate apical hook development in Arabidopsis (Arabidopsis thaliana). Exogenous application of methyl jasmonate (MeJA) repressed the expression of the rate-limiting BR biosynthetic gene DWARF4 (DWF4) in a process relying on 3 key JA-dependent transcription factors, MYC2, MYC3, and MYC4. We demonstrated that MYC2 interacts with the critical BR-activated transcription factor BRASSINAZOLE RESISTANT 1 (BZR1), disrupting the association of BZR1 with its partner transcription factors, such as those of the PHYTOCHROME INTERACTING FACTOR (PIF) family and downregulating the expression of their target genes, such as WAVY ROOT GROWTH 2 (WAG2), encoding a protein kinase essential for apical hook development. Our results indicate that JAs not only repress the expression of BR biosynthetic gene DWF4 but, more importantly, attenuate BR signaling by inhibiting the transcriptional activation of BZR1 by MYC2 during apical hook development.
Topics: Arabidopsis Proteins; Brassinosteroids; Arabidopsis; Transcription Factors; Gene Expression Regulation, Plant
PubMed: 37467431
DOI: 10.1093/plphys/kiad399 -
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 -
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 -
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 -
Periodontology 2000 Feb 2024After tooth loss in the posterior area of the maxilla, sinus floor elevation is often required to compensate the vertical bone loss due to sinus pneumatization. This... (Review)
Review
After tooth loss in the posterior area of the maxilla, sinus floor elevation is often required to compensate the vertical bone loss due to sinus pneumatization. This narrative review reports on the potential benefits of autologous platelet concentrates (APCs) during this procedure. As for transcrestal approach, APCs have been used as "sole" substitute/graft. However, because of the low number of clinical trials available with PRGF, and even none for PRP, no definitive conclusions can be made regarding their efficacy. The number of studies on the use of L-PRF were outnumbered indicating good feasibility for vertical bone gain, with a high implant survival rate and a low degree of complications. PRP and PRGF have not been studied as a "single/sole" substitute for a one-stage lateral window approach, probably because of the weak physical characteristics of the membranes. L-PRF alone appears to be a predictable grafting material for lateral maxillary sinus grafting and a reduced RBH should not be considered as a risk factor. Compared to a "standard" bone substitute L-PRF shows slightly less vertical bone gain (consider enough membrane application and use of bony window as new sinus floor roof over the implant apices), enhanced early resorption (first 6 months after application), but a similar stable bone gain afterward. For a two-stage lateral window approach, APCs "alone" cannot be recommended, due to their weak withstand to the sinus pneumatization forces. APCs combined with bone substitutes seem to accelerate bone formation, without any additional benefits on the long-term new bone gain. The use of L-PRF membranes for the treatment of perforations appears to be an effective treatment option, but further clinical studies are needed to confirm this. Even though the abovementioned statements are based on large numbers of studies, additional RCTs comparing APCs with different types of grafting procedures for sinus elevation are needed.
PubMed: 38363055
DOI: 10.1111/prd.12554 -
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 -
JACC. Cardiovascular Imaging May 2024There is no acceptable maximum wall thickness (MWT) threshold for diagnosing apical hypertrophic cardiomyopathy (ApHCM), with guidelines referring to ≥15 mm MWT for...
BACKGROUND
There is no acceptable maximum wall thickness (MWT) threshold for diagnosing apical hypertrophic cardiomyopathy (ApHCM), with guidelines referring to ≥15 mm MWT for all hypertrophic cardiomyopathy subtypes. A normal myocardium naturally tapers apically; a fixed diagnostic threshold fails to account for this. Using cardiac magnetic resonance, "relative" ApHCM has been described with typical electrocardiographic features, loss of apical tapering, and cavity obliteration but also with MWT <15 mm.
OBJECTIVES
The authors aimed to define normal apical wall thickness thresholds in healthy subjects and use these to accurately identify ApHCM.
METHODS
The following healthy subjects were recruited: healthy UK Biobank imaging substudy subjects (n = 4,112) and an independent healthy volunteer group (n = 489). A clinically defined disease population of 104 ApHCM subjects was enrolled, with 72 overt (MWT ≥15 mm) and 32 relative (MWT <15 mm but typical electrocardiographic/imaging findings) ApHCM subjects. Cardiac magnetic resonance-derived MWT was measured in 16 segments using a published clinically validated machine learning algorithm. Segmental normal reference ranges were created and indexed (for age, sex, and body surface area), and diagnostic performance was assessed.
RESULTS
In healthy cohorts, there was no clinically significant age-related difference for apical wall thickness. There were sex-related differences, but these were not clinically significant after indexing to body surface area. Therefore, segmental reference ranges for apical hypertrophy required indexing to body surface area only (not age or sex). The upper limit of normal (the largest of the 4 apical segments measured) corresponded to a maximum apical MWT in healthy subjects of 5.2 to 5.6 mm/m with an accuracy of 0.94 (the unindexed equivalent being 11 mm). This threshold was categorized as abnormal in 99% (71/72) of overt ApHCM patients, 78% (25/32) of relative ApHCM patients, 3% (122/4,112) of UK Biobank subjects, and 3% (13/489) of healthy volunteers.
CONCLUSIONS
Per-segment indexed apical wall thickness thresholds are highly accurate for detecting apical hypertrophy, providing confidence to the reader to diagnose ApHCM in those not reaching current internationally recognized criteria.
Topics: Humans; Female; Male; Cardiomyopathy, Hypertrophic; Middle Aged; Predictive Value of Tests; Adult; Reproducibility of Results; Aged; Case-Control Studies; Electrocardiography; Magnetic Resonance Imaging; United Kingdom; Magnetic Resonance Imaging, Cine; Machine Learning; Healthy Volunteers; Apical Hypertrophic Cardiomyopathy
PubMed: 37831014
DOI: 10.1016/j.jcmg.2023.07.012 -
The Cochrane Database of Systematic... May 2024Dental pain can have a detrimental effect on quality of life. Symptomatic apical periodontitis and acute apical abscess are common causes of dental pain and arise from... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dental pain can have a detrimental effect on quality of life. Symptomatic apical periodontitis and acute apical abscess are common causes of dental pain and arise from an inflamed or necrotic dental pulp, or infection of the pulpless root canal system. Clinical guidelines recommend that the first-line treatment for these conditions should be removal of the source of inflammation or infection by local operative measures, and that systemic antibiotics are currently only recommended for situations where there is evidence of spreading infection (cellulitis, lymph node involvement, diffuse swelling) or systemic involvement (fever, malaise). Despite this, there is evidence that dentists frequently prescribe antibiotics in the absence of these signs. There is concern that this could contribute to the development of antibiotic-resistant bacteria. This review is the second update of the original version first published in 2014.
OBJECTIVES
To evaluate the effects of systemic antibiotics provided with or without surgical intervention (such as extraction, incision and drainage of a swelling, or endodontic treatment), with or without analgesics, for symptomatic apical periodontitis and acute apical abscess in adults.
SEARCH METHODS
We searched Cochrane Oral Health's Trials Register (26 February 2018 (discontinued)), CENTRAL (2022, Issue 10), MEDLINE Ovid (23 November 2022), Embase Ovid (23 November 2022), CINAHL EBSCO (25 November 2022) and two trials registries, and performed a grey literature search. There were no restrictions on language or date of publication.
SELECTION CRITERIA
Randomised controlled trials of systemic antibiotics in adults with a clinical diagnosis of symptomatic apical periodontitis or acute apical abscess, with or without surgical intervention (considered in this situation to be extraction, incision and drainage, or endodontic treatment) and with or without analgesics.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias. We used a fixed-effect model in the meta-analysis as there were fewer than four studies. We contacted study authors to request missing information. We used GRADE criteria to assess the certainty of the evidence.
MAIN RESULTS
There was one new completed trial on this topic since the last update in 2018. In total, we included three trials with 134 participants. Systemic antibiotics versus placebo with surgical intervention and analgesics for symptomatic apical periodontitis or acute apical abscess One trial (72 participants) compared the effects of a single preoperative dose of clindamycin versus a matched placebo when provided with a surgical intervention (endodontic chemo-mechanical debridement and filling) and analgesics to adults with symptomatic apical periodontitis. We assessed this study at low risk of bias. There were no differences in participant-reported pain or swelling across trial arms at any time point assessed. The median values for pain (numerical rating scale 0 to 10) were 3.0 in both groups at 24 hours (P = 0.219); 1.0 in the antibiotic group versus 2.0 in the control group at 48 hours (P = 0.242); and 0 in both groups at 72 hours and seven days (P = 0.116 and 0.673, respectively). The risk ratio of swelling when comparing preoperative antibiotic to placebo was 0.50 (95% confidence interval (CI) 0.10 to 2.56; P = 0.41). The certainty of evidence for all outcomes in this comparison was low. Two trials (62 participants) compared the effects of a seven-day course of oral phenoxymethylpenicillin (penicillin VK) versus a matched placebo when provided with a surgical intervention (total or partial endodontic chemo-mechanical debridement) and analgesics to adults with acute apical abscess or symptomatic necrotic tooth. Participants in both trials also received oral analgesics. We assessed one study at high risk of bias and the other at unclear risk of bias. There were no differences in participant-reported pain or swelling at any time point assessed. The mean difference for pain (short ordinal numerical scale 0 to 3, where 0 was no pain) was -0.03 (95% CI -0.53 to 0.47) at 24 hours; 0.32 (95% CI -0.22 to 0.86) at 48 hours; and 0.08 (95% CI -0.38 to 0.54) at 72 hours. The standardised mean difference for swelling was 0.27 (95% CI -0.23 to 0.78) at 24 hours; 0.04 (95% CI -0.47 to 0.55) at 48 hours; and 0.02 (95% CI -0.49 to 0.52) at 72 hours. The certainty of evidence for all the outcomes in this comparison was very low. Adverse effects, as reported in two studies, were diarrhoea (one participant in the placebo group), fatigue and reduced energy postoperatively (one participant in the antibiotic group) and dizziness preoperatively (one participant in the antibiotic group). Systemic antibiotics without surgical intervention for adults with symptomatic apical periodontitis or acute apical abscess We found no studies that compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults.
AUTHORS' CONCLUSIONS
The evidence suggests that preoperative clindamycin for adults with symptomatic apical periodontitis results in little to no difference in participant-reported pain or swelling at any of the time points included in this review when provided with chemo-mechanical endodontic debridement and filling under local anaesthesia. The evidence is very uncertain about the effect of postoperative phenoxymethylpenicillin for adults with localised apical abscess or a symptomatic necrotic tooth when provided with chemo-mechanical debridement and oral analgesics. We found no studies which compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults.
Topics: Adult; Humans; Acute Disease; Anti-Bacterial Agents; Bias; Drainage; Periapical Abscess; Periapical Periodontitis; Randomized Controlled Trials as Topic; Toothache
PubMed: 38712714
DOI: 10.1002/14651858.CD010136.pub4