-
The Plant Cell Jul 2024Lignin production marked a milestone in vascular plant evolution, and the emergence of syringyl (S) lignin is lineage specific. S-lignin biosynthesis in angiosperms,...
Lignin production marked a milestone in vascular plant evolution, and the emergence of syringyl (S) lignin is lineage specific. S-lignin biosynthesis in angiosperms, mediated by ferulate 5-hydroxylase (F5H, CYP84A1), has been considered a recent evolutionary event. F5H uniquely requires the cytochrome b5 protein CB5D as an obligatory redox partner for catalysis. However, it remains unclear how CB5D functionality originated and whether it coevolved with F5H. We reveal here the ancient evolution of CB5D-type function supporting F5H-catalyzed S-lignin biosynthesis. CB5D emerged in charophyte algae, the closest relatives of land plants, and is conserved and proliferated in embryophytes, especially in angiosperms, suggesting functional diversification of the CB5 family before terrestrialization. A sequence motif containing acidic amino residues in Helix 5 of the CB5 heme-binding domain contributes to the retention of CB5D function in land plants but not in algae. Notably, CB5s in the S-lignin-producing lycophyte Selaginella lack these residues, resulting in no CB5D-type function. An independently evolved S-lignin biosynthetic F5H (CYP788A1) in Selaginella relies on NADPH-dependent cytochrome P450 reductase as sole redox partner, distinct from angiosperms. These results suggest that angiosperm F5Hs coopted the ancient CB5D, forming a modern cytochrome P450 monooxygenase system for aromatic ring meta-hydroxylation, enabling the reemergence of S-lignin biosynthesis in angiosperms.
Topics: Lignin; Cytochromes b5; Plant Proteins; Phylogeny; Cytochrome P-450 Enzyme System; Evolution, Molecular; Magnoliopsida; Embryophyta; Charophyceae
PubMed: 38657101
DOI: 10.1093/plcell/koae120 -
Annals of Clinical and Translational... Jun 2024Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterized by recurrent ischemic/hemorrhagic strokes due to progressive occlusion of the intracranial...
OBJECTIVE
Moyamoya angiopathy (MA) is a rare cerebrovascular disorder characterized by recurrent ischemic/hemorrhagic strokes due to progressive occlusion of the intracranial carotid arteries. The lack of reliable disease severity biomarkers led us to investigate molecular features of a Caucasian cohort of MA patients.
METHODS
The participants consisted of 30 MA patients and 40 controls. We measured cerebrospinal fluid (CSF) levels of angiogenic/inflammatory factors (ELISA). We then applied quantitative real-time PCR on cerebral artery specimens for expression analyses of angiogenic factors. By an immunoassay based on microfluidic technology, we examined the potential correlations between plasma protein expression and MA clinical progression. A RNA interference approach toward Ring Finger Protein 213 (RNF213) and a tube formation assay were applied in cellular model.
RESULTS
We detected a statistically significant (p < 0.000001) up-regulation of Angiopoietin-2 (Ang-2) in CSF and stenotic middle cerebral arteries (RQ >2) of MA patients compared to controls. A high Ang-2 plasma concentration (p = 0.018) was associated with unfavorable outcome in a subset of MA patients. ROC curve analyses indicated Ang-2 as diagnostic CSF biomarker (>3741 pg/mL) and prognostic plasma biomarker (>1162 pg/mL), to distinguish stable-from-progressive MA. Consistently, MA cellular model showed a significant up-regulation (RQ >2) of Ang-2 in RNF213 silenced condition.
INTERPRETATION
Our results pointed out Ang-2 as a reliable biomarker mirroring arterial steno-occlusion and vascular instability of MA in CSF and blood, providing a candidate factor for patient stratification. This pilot study may pave the way to the validation of a biomarker to identify progressive MA patients deserving a specific treatment path.
Topics: Humans; Moyamoya Disease; Angiopoietin-2; Male; Female; Adult; Middle Aged; Prognosis; Biomarkers; Ubiquitin-Protein Ligases; Young Adult; Adenosine Triphosphatases
PubMed: 38655722
DOI: 10.1002/acn3.52076 -
Korean Journal of Anesthesiology Apr 2024Bleeding incidents during percutaneous dilatational tracheostomy are concerning, and most cases occur in patients with unrecognized and unanticipated anatomical...
BACKGROUND
Bleeding incidents during percutaneous dilatational tracheostomy are concerning, and most cases occur in patients with unrecognized and unanticipated anatomical variations in the vascular anatomy. However, the extent of this variation remains unclear. To address this knowledge gap, our study aimed to comprehensively map laryngeal vascular anatomy in a cohort of adult patients.
METHODS
Ultrasound assessments of the soft tissue in the neck were performed, spanning from the thyroid cartilage to the third tracheal ring and extending 2 cm laterally on both sidesperformed. We subdivided this area into 12 zones comprising four medial and eight lateral sections. A pre-planned form was used to document the presence of arteries or veins in each zone. The results are reported as odds ratios, 95% CIs, and corresponding P-values.
RESULTS
Five-hundred patients were enrolled from August 14, 2023, to November 13, 2023, at the University Hospital of Padua. Arteries and veins were identified in all investigated zones (varying from a minimum of 1.0%-46.4%). The presence of invessels progressively increased from the cricothyroid membrane to the third tracheal ring and from the midline to the paramedian laryngeal area.
CONCLUSIONS
Given the prevalence of arteries and veins, particularly in areas where tracheostomies are commonly performed, we strongly advocate for routine ultrasound assessments before such procedures are performed.
PubMed: 38653329
DOI: 10.4097/kja.23900 -
Proceedings of the National Academy of... Apr 2024The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These...
The complex interplay between malignant cells and the cellular and molecular components of the tumor stroma is a key aspect of cancer growth and development. These tumor-host interactions are often affected by soluble bioactive molecules such as proteoglycans. Decorin, an archetypical small leucine-rich proteoglycan primarily expressed by stromal cells, affects cancer growth in its soluble form by interacting with several receptor tyrosine kinases (RTK). Overall, decorin leads to a context-dependent and protracted cessation of oncogenic RTK activity by attenuating their ability to drive a prosurvival program and to sustain a proangiogenic network. Through an unbiased transcriptomic analysis using deep RNAseq, we identified that decorin down-regulated a cluster of tumor-associated genes involved in lymphatic vessel (LV) development when systemically delivered to mice harboring breast carcinoma allografts. We found that Lyve1 and Podoplanin, two established markers of LVs, were markedly suppressed at both the mRNA and protein levels, and this suppression correlated with a significant reduction in tumor LVs. We further identified that soluble decorin, but not its homologous proteoglycan biglycan, inhibited LV sprouting in an ex vivo 3D model of lymphangiogenesis. Mechanistically, we found that decorin interacted with vascular endothelial growth factor receptor 3 (VEGFR3), the main lymphatic RTK, and its activity was required for the decorin-mediated block of lymphangiogenesis. Finally, we identified that Lyve1 was in part degraded via decorin-evoked autophagy in a nutrient- and energy-independent manner. These findings implicate decorin as a biological factor with antilymphangiogenic activity and provide a potential therapeutic agent for curtailing breast cancer growth and metastasis.
Topics: Decorin; Lymphangiogenesis; Animals; Mice; Humans; Female; Breast Neoplasms; Lymphatic Vessels; Cell Line, Tumor; Disease Progression; Vesicular Transport Proteins; Membrane Glycoproteins; Gene Expression Regulation, Neoplastic
PubMed: 38652741
DOI: 10.1073/pnas.2317760121 -
Cureus Mar 2024Embolization of entrapped intracardiac air represents a significant risk to the patient undergoing open-heart surgery. Entrapment of as little as 0.5 mL of gas in the...
Embolization of entrapped intracardiac air represents a significant risk to the patient undergoing open-heart surgery. Entrapment of as little as 0.5 mL of gas in the heart can cause temporary myocardial dysfunction, cardiac arrhythmias, and systemic emboli. In contrast, larger emboli can disrupt the evaluation of heart function by limiting visualization during echocardiography. We present the case of a 67-year-old male who presented with dizziness, nausea, and chest pain. A left heart catheterization revealed multi-vessel disease. Undergoing general anesthesia, the patient received three-vessel coronary artery bypass grafting, mitral valve repair, ring annuloplasty, and left atrial appendage closure. Upon aortic unclamping, transgastric echocardiography showed significant gas almost wholly obscuring the left heart chambers despite de-airing maneuvers. Successful resolution relied upon higher mean blood pressure and time, demonstrating the importance of intraoperative imaging and interdisciplinary collaboration.
PubMed: 38646393
DOI: 10.7759/cureus.56525 -
Veterinary Surgery : VS Apr 2024The objective was to describe the successful thoracoscopic treatment of esophageal entrapment resulting from a vascular ring anomaly (VRA) comprising a persistent right...
OBJECTIVE
The objective was to describe the successful thoracoscopic treatment of esophageal entrapment resulting from a vascular ring anomaly (VRA) comprising a persistent right aortic arch (PRAA) and left ligamentum arteriosum (LA) in a Babydoll sheep wether.
STUDY DESIGN
Case report.
ANIMAL
Eight month old Babydoll sheep wether, 13 kg.
METHODS
The patient presented with a weight half that of its sibling, persistent regurgitation following eating, and delayed growth noted from the age of approximately 2 months, coinciding with the introduction of solid feed into the diet. Plain thoracic radiographs were within normal limits but computed tomography angiography (CTA) confirmed multiple congenital vascular anomalies. The primary finding was esophageal and tracheal entrapment by a PRAA and left LA. Thoracoscopic transection of the LA was performed with a bipolar vessel sealing device with the aid of transesophageal endoscopy.
RESULTS
Immediate improvement in attitude and absence of regurgitation were observed. The patient was discharged and subsequently reintroduced to grazing and long-stem hay, which were previously not tolerated. By 6 months post discharge, the patient's weight was 36 kg, comparable to an age-matched sibling and considered appropriate for the stage of growth.
CONCLUSION
Thoracoscopic transection of the LA in sheep is a feasible treatment for esophageal compression resulting from a VRA. Surgical intervention resolved the clinical signs and allowed normal digestive rumination, restoring bidirectional esophageal function in a ruminant.
PubMed: 38641961
DOI: 10.1111/vsu.14094 -
Surgical Endoscopy May 2024Virtual reality is a frequently chosen method for learning the basics of robotic surgery. However, it is unclear whether tissue handling is adequately trained in VR... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Virtual reality is a frequently chosen method for learning the basics of robotic surgery. However, it is unclear whether tissue handling is adequately trained in VR training compared to training on a real robotic system.
METHODS
In this randomized controlled trial, participants were split into two groups for "Fundamentals of Robotic Surgery (FRS)" training on either a DaVinci VR simulator (VR group) or a DaVinci robotic system (Robot group). All participants completed four tasks on the DaVinci robotic system before training (Baseline test), after proficiency in three FRS tasks (Midterm test), and after proficiency in all FRS tasks (Final test). Primary endpoints were forces applied across tests.
RESULTS
This trial included 87 robotic novices, of which 43 and 44 participants received FRS training in VR group and Robot group, respectively. The Baseline test showed no significant differences in force application between the groups indicating a sufficient randomization. In the Midterm and Final test, the force application was not different between groups. Both groups displayed sufficient learning curves with significant improvement of force application. However, the Robot group needed significantly less repetitions in the three FRS tasks Ring tower (Robot: 2.48 vs. VR: 5.45; p < 0.001), Knot Tying (Robot: 5.34 vs. VR: 8.13; p = 0.006), and Vessel Energy Dissection (Robot: 2 vs. VR: 2.38; p = 0.001) until reaching proficiency.
CONCLUSION
Robotic tissue handling skills improve significantly and comparably after both VR training and training on a real robotic system, but training on a VR simulator might be less efficient.
Topics: Humans; Robotic Surgical Procedures; Clinical Competence; Female; Male; Virtual Reality; Prospective Studies; Adult; Simulation Training; Learning Curve; Young Adult
PubMed: 38632120
DOI: 10.1007/s00464-024-10842-7 -
Pediatric Pulmonology Apr 2024Tracheobronchomalacia (TBM) is characterized by excessive dynamic airway collapse. Severe TBM can be associated with substantial morbidity. Children with secondary TBM...
BACKGROUND
Tracheobronchomalacia (TBM) is characterized by excessive dynamic airway collapse. Severe TBM can be associated with substantial morbidity. Children with secondary TBM associated with esophageal atresia/tracheoesophageal fistula (EA/TEF) and vascular-related airway compression (VRAC) demonstrate clinical improvement following airway pexy surgery. It is unclear if children with severe primary TBM, without secondary etiologies (EA/TEF, vascular ring, intrinsic pulmonary pathology, or complex cardiac disease) demonstrate clinical improvement following airway pexy surgery.
MATERIALS AND METHODS
The study cohort consisted of 73 children with severe primary TBM who underwent airway pexy surgery between 2013 and 2020 at Boston Children's Hospital. Pre- and postoperative symptoms as well as bronchoscopic findings were compared with Fisher exact test for categorical data and Student's t-test for continuous data.
RESULTS
Statistically significant improvements in clinical symptoms were observed, including cough, noisy breathing, prolonged respiratory infections, pneumonias, exercise intolerance, cyanotic spells, brief resolved unexplained events (BRUE), and noninvasive positive pressure ventilation (NIPPV) dependence. No significant differences were seen regarding oxygen dependence, ventilator dependence, or respiratory distress requiring NIPPV. Comparison of pre- and postoperative dynamic bronchoscopy findings revealed statistically significant improvement in the percent of airway collapse in all anatomic locations except at the level of the upper trachea (usually not malacic). Despite some initial improvements, 21 (29%) patients remained symptomatic and underwent additional airway pexies with improvement in symptoms.
CONCLUSION
Airway pexy surgery resulted in significant improvement in clinical symptoms and bronchoscopic findings for children with severe primary TBM; however, future prospective and long-term studies are needed to confirm this benefit.
PubMed: 38629381
DOI: 10.1002/ppul.27012 -
The American Journal of Cardiology Jun 2024Development of functional tricuspid regurgitation (TR) because of chronic mitral disease and subsequent heart failure is common. However, the effect of TR on clinical...
Development of functional tricuspid regurgitation (TR) because of chronic mitral disease and subsequent heart failure is common. However, the effect of TR on clinical outcomes after transcatheter mitral valve replacement (TMVR) remains unclear. We aimed to evaluate the impact of baseline TR on outcomes after TMVR. This was a single-center, retrospective analysis of patients who received valve-in-valve or valve-in-ring TMVR between 2012 and 2022. Patients were categorized into none/mild TR and moderate/severe TR based on baseline echocardiography. The primary outcome was 3 years all-cause death and the secondary outcomes were in-hospital events. Of the 135 patients who underwent TMVR, 64 (47%) exhibited none/mild TR at baseline, whereas 71 (53%) demonstrated moderate/severe TR. There were no significant differences in in-hospital events between the groups. At 3 years, the moderate/severe TR group exhibited a significantly increased risk of all-cause death (adjusted hazard ratio 3.37, 95% confidence interval 1.35 to 8.41, p = 0.009). When patients with baseline moderate/severe TR were stratified by echocardiography at 30 days into improved (36%) and nonimproved (64%) TR groups, although limited by small sample size, there was no significant difference in 3-year all-cause mortality (p = 0.48). In conclusion, this study investigating the impact of baseline TR on clinical outcomes revealed that moderate/severe TR is prevalent in those who underwent TMVR and is an independent predictor of 3-year all-cause mortality. Earlier mitral valve intervention before the development of significant TR may play a pivotal role in improving outcomes after TMVR.
Topics: Humans; Male; Tricuspid Valve Insufficiency; Female; Retrospective Studies; Aged; Heart Valve Prosthesis Implantation; Mitral Valve Insufficiency; Echocardiography; Cardiac Catheterization; Severity of Illness Index; Treatment Outcome; Cause of Death; Postoperative Complications; Aged, 80 and over; Mitral Valve
PubMed: 38604492
DOI: 10.1016/j.amjcard.2024.03.036 -
Revue Medicale de Liege Apr 2024We report the case of a 36-year-old female whose dysphagia revealed a congenital anomaly of the thoracic aorta: the right aortic arch with mirror image branching. This...
We report the case of a 36-year-old female whose dysphagia revealed a congenital anomaly of the thoracic aorta: the right aortic arch with mirror image branching. This is a rare embryonic developmental anomaly where the aorta wraps around the right bronchus and the supra-aortic trunks emerge from the arch in the opposite order to normal. Most of the patients are asymptomatic unless there is a significant compression of mediastinal structures. Major compression of the esophagus or trachea, aneurysmal disease, dissection of the thoracic aorta, or the presence of a Kommerell diverticulum larger than 2 cm may require a surgical repair. There is no standard treatment and it must be adapted to the clinical presentation and the anatomic configuration of each patient. Our patient did not receive any treatment for her condition.
Topics: Female; Humans; Adult; Aorta, Thoracic; Deglutition Disorders; Mediastinum; Subclavian Artery
PubMed: 38602205
DOI: No ID Found