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1.
J Phys Chem A ; 128(25): 4976-4983, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38850250

RESUMO

Nonadiabatic interaction of adsorbate nuclear motion with the continuum of electronic states is known to affect the dynamics of chemical reactions at metal surfaces. A large body of work has probed the fundamental mechanisms of such interactions for atomic and diatomic molecules at surfaces. In polyatomic molecules, the possibility of mode-specific damping of vibrational motion due to the effects of electronic friction raises the question of whether such interactions could profoundly affect the outcome of chemistry at surfaces by selectively removing energy from a particular intramolecular adsorbate mode. However, to date, there have not been any fundamental experiments demonstrating nonadiabatic electron-vibration coupling in a polyatomic molecule at a surface. In this work, we scatter excited metastable formaldehyde and formaldehyde-d2 from a low work function surface and detect ejected exoelectrons that accompany molecular relaxation. The exoelectron ejection efficiency exhibits a strong dependence on the vibrational mode that is excited: out-of-plane bending excitation (ν4) leads to significantly more exoelectrons than does CO stretching excitation (ν2). The results provide clear evidence for mode-specific energy transfer from vibration to surface electrons.

2.
bioRxiv ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38854152

RESUMO

Precise control of morphogen signaling levels is essential for proper development. An outstanding question is: what mechanisms ensure proper morphogen activity and correct cellular responses? Previous work has identified Semaphorin (SEMA) receptors, Neuropilins (NRPs) and Plexins (PLXNs), as positive regulators of the Hedgehog (HH) signaling pathway. Here, we provide evidence that NRPs and PLXNs antagonize Wnt signaling in both fibroblasts and epithelial cells. Further, Nrp1/2 deletion in fibroblasts results in elevated baseline Wnt pathway activity and increased maximal responses to Wnt stimulation. Notably, and in contrast to HH signaling, SEMA receptor-mediated Wnt antagonism is independent of primary cilia. Mechanistically, PLXNs and NRPs act downstream of Dishevelled (DVL) to destabilize ß-catenin (CTNNB1) in a proteosome-dependent manner. Further, NRPs, but not PLXNs, act in a GSK3ß/CK1-dependent fashion to antagonize Wnt signaling, suggesting distinct repressive mechanisms for these SEMA receptors. Overall, this study identifies SEMA receptors as novel Wnt pathway antagonists that may also play larger roles integrating signals from multiple inputs.

3.
Glob Chang Biol ; 30(6): e17374, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38863181

RESUMO

In this Technical Advance, we describe a novel method to improve ecological interpretation of remotely sensed vegetation greenness measurements that involved sampling 24,395 Landsat pixels (30 m) across 639 km of Alaska's central Brooks Range. The method goes well beyond the spatial scale of traditional plot-based sampling and thereby more thoroughly relates ground-based observations to satellite measurements. Our example dataset illustrates that, along the boreal-Arctic boundary, vegetation with the greatest Landsat Normalized Difference Vegetation Index (NDVI) is taller than 1 m, woody, and deciduous; whereas vegetation with lower NDVI tends to be shorter, evergreen, or non-woody. The field methods and associated analyses advance efforts to inform satellite data with ground-based vegetation observations using field samples collected at spatial scales that closely match the resolution of remotely sensed imagery.


Assuntos
Imagens de Satélites , Tundra , Alaska , Regiões Árticas , Tecnologia de Sensoriamento Remoto/métodos , Taiga , Monitoramento Ambiental/métodos
4.
Infection ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856806

RESUMO

PURPOSE: Most data regarding infective endocarditis (IE) after transcatheter aortic valve implantation (TAVI) comes from TAVI registries, rather than IE dedicated cohorts. The objective of our study was to compare the clinical and microbiological profile, imaging features and outcomes of patients with IE after SAVR with a biological prosthetic valve (IE-SAVR) and IE after TAVI (IE-TAVI) from 6 centres with an Endocarditis Team (ET) and broad experience in IE. METHODS: Retrospective analysis of prospectively collected data. From the time of first TAVI implantation in each centre to March 2021, all consecutive patients admitted for IE-SAVR or IE-TAVI were prospectively enrolled. Follow-up was monitored during admission and at 12 months after discharge. RESULTS: 169 patients with IE-SAVR and 41 with IE-TAVI were analysed. Early episodes were more frequent among IE-TAVI. Clinical course during hospitalization was similar in both groups, except for a higher incidence of atrioventricular block in IE-SAVR. The most frequently causative microorganisms were S. epidermidis, Enterococcus spp. and S. aureus in both groups. Periannular complications were more frequent in IE-SAVR. Cardiac surgery was performed in 53.6% of IE-SAVR and 7.3% of IE-TAVI (p=0.001), despite up to 54.8% of IE-TAVI patients had an indication. No differences were observed about death during hospitalization (32.7% vs 35.0%), and at 1-year follow-up (41.8% vs 37.5%), regardless of whether the patient underwent surgery or not. CONCLUSION: Patients with IE-TAVI had a higher incidence of early prosthetic valve IE. Compared to IE-SAVR, IE-TAVI patients underwent cardiac surgery much less frequently, despite having surgical indications. However, in-hospital and 1-year mortality rate was similar between both groups.

5.
Rev Esp Quimioter ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38934492

RESUMO

OBJECTIVE: Our aim was to analyse the relation between serial values of the indocyanine green plasma disappearance rate (ICG-PDR) with hospital mortality in the first 48 hours of ICU admission in patients with septic shock. METHODS: A prospective observational study was carried out over 12 months of patients admitted to the ICU with septic shock. Each patient underwent noninvasive determination of ICG-PDR at 24 and 48 hours with the LiMON® module. Follow-up was performed until hospital discharge or exitus. RESULTS: 63 patients. Age 61.1±12.3 years. 60.3% men. SOFA score on admission 8.7±3.3, APACHE II score was 27.9±10.7 points. A total of 44.4% of patients died. The ICG-PDR values in the first 24 hours of ICU admission were lower in nonsurvivors: 10.5 (5.7-13.0)%/min vs. 15.9 (11.4-28.0)%/min, p <0.001. Furthermore, in nonsurvivors, there was no improvement in ICG-PDR between 24 h and 48 h, while in survivors, there was an increase of 25%: 15.9 (11.4-28.0)%/min and 20.9 (18.0-27.0)%/min, p=0.020. The silhouette measure of ICG-PDR cohesion and separation for the clusters analysed (nonsurvivors and survivors) was satisfactory (0.6). ICG-PDR<11.7%/min was related to in-hospital mortality, ICG-PDR> 18%/min to survival, and the interval between 11.7% and 18%/min covered a range of uncertainty. In the two-stage cluster, ICG-PDR, SOFA and APACHE II present satisfactory predictive scores 24 hours after patient admission. CONCLUSIONS: ICG-PDR in our setting is a useful clinical prognostic tool and could optimise the decision tree in patients with septic shock.

6.
ACS Appl Mater Interfaces ; 16(23): 29657-29671, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38815127

RESUMO

The growing number of acute drug abuse overdoses demands the development of innovative detoxification strategies for emergency purposes. In this study, an innovative approach for the application of porous Zr-based metal-organic frameworks for the treatment of acute overdoses of popular drugs of abuse including amphetamine, methamphetamine, cocaine, and MDMA is presented. A comprehensive approach determining the efficacy and the kinetics of drug removal, considering dosage, adsorption time, and adsorption mechanisms, was tested and corroborated with density functional theory (DFT) modeling. The experimental results showed high removal efficiency reaching up to 90% in the case of the application of the NU-1000 metal-organic framework. The difference Raman spectroscopy method presented in this study corroborated with DFT-based vibrational analysis allows the detection of drug adsorbed in the MOF framework even with as low a concentration as 5 mg/g. Additionally, the drug adsorption mechanisms were modeled with DFT, showing the π-π stacking in a vast majority of considered cases. The performance and influence on the living organisms were evaluated throughout the in vitro and in vivo experiments, indicating that Zr-based MOFs could serve as efficient, organic, safe drug adsorbents.


Assuntos
Estruturas Metalorgânicas , Zircônio , Estruturas Metalorgânicas/química , Adsorção , Zircônio/química , Teoria da Densidade Funcional , Animais , Porosidade , Metanfetamina/química
7.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38731994

RESUMO

The mechanism of ethylene (ET)-regulated salinity stress response remains largely unexplained, especially for semi-halophytes and halophytes. Here, we present the results of the multifaceted analysis of the model semi-halophyte Mesembryanthemum crystallinum L. (common ice plant) ET biosynthesis pathway key components' response to prolonged (14 days) salinity stress. Transcriptomic analysis revealed that the expression of 3280 ice plant genes was altered during 14-day long salinity (0.4 M NaCl) stress. A thorough analysis of differentially expressed genes (DEGs) showed that the expression of genes involved in ET biosynthesis and perception (ET receptors), the abscisic acid (ABA) catabolic process, and photosynthetic apparatus was significantly modified with prolonged stressor presence. To some point this result was supported with the expression analysis of the transcript amount (qPCR) of key ET biosynthesis pathway genes, namely ACS6 (1-aminocyclopropane-1-carboxylate synthase) and ACO1 (1-aminocyclopropane-1-carboxylate oxidase) orthologs. However, the pronounced circadian rhythm observed in the expression of both genes in unaffected (control) plants was distorted and an evident downregulation of both orthologs' was induced with prolonged salinity stress. The UPLC-MS analysis of the ET biosynthesis pathway rate-limiting semi-product, namely of 1-aminocyclopropane-1-carboxylic acid (ACC) content, confirmed the results assessed with molecular tools. The circadian rhythm of the ACC production of NaCl-treated semi-halophytes remained largely unaffected by the prolonged salinity stress episode. We speculate that the obtained results represent an image of the steady state established over the past 14 days, while during the first hours of the salinity stress response, the view could be completely different.


Assuntos
Etilenos , Regulação da Expressão Gênica de Plantas , Estresse Salino , Plantas Tolerantes a Sal , Etilenos/biossíntese , Etilenos/metabolismo , Plantas Tolerantes a Sal/genética , Plantas Tolerantes a Sal/metabolismo , Mesembryanthemum/metabolismo , Mesembryanthemum/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Vias Biossintéticas , Perfilação da Expressão Gênica/métodos , Ácido Abscísico/metabolismo , Salinidade , Transcriptoma
8.
Hum Mol Genet ; 33(R1): R26-R33, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38779774

RESUMO

Mitochondria are vital organelles present in almost all eukaryotic cells. Although most of the mitochondrial proteins are nuclear-encoded, mitochondria contain their own genome, whose proper expression is necessary for mitochondrial function. Transcription of the human mitochondrial genome results in the synthesis of long polycistronic transcripts that are subsequently processed by endonucleases to release individual RNA molecules, including precursors of sense protein-encoding mRNA (mt-mRNA) and a vast amount of antisense noncoding RNAs. Because of mitochondrial DNA (mtDNA) organization, the regulation of individual gene expression at the transcriptional level is limited. Although transcription of most protein-coding mitochondrial genes occurs with the same frequency, steady-state levels of mature transcripts are different. Therefore, post-transcriptional processes are important for regulating mt-mRNA levels. The mitochondrial degradosome is a complex composed of the RNA helicase SUV3 (also known as SUPV3L1) and polynucleotide phosphorylase (PNPase, PNPT1). It is the best-characterized RNA-degrading machinery in human mitochondria, which is primarily responsible for the decay of mitochondrial antisense RNA. The mechanism of mitochondrial sense RNA decay is less understood. This review aims to provide a general picture of mitochondrial genome expression, with a particular focus on mitochondrial RNA (mtRNA) degradation.


Assuntos
Mitocôndrias , Polirribonucleotídeo Nucleotidiltransferase , Estabilidade de RNA , RNA Mitocondrial , Humanos , Mitocôndrias/metabolismo , Mitocôndrias/genética , Estabilidade de RNA/genética , Polirribonucleotídeo Nucleotidiltransferase/metabolismo , Polirribonucleotídeo Nucleotidiltransferase/genética , RNA Mitocondrial/metabolismo , RNA Mitocondrial/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Antissenso/genética , RNA Antissenso/metabolismo , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , RNA Helicases/metabolismo , RNA Helicases/genética , RNA/metabolismo , RNA/genética , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/genética , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Endorribonucleases , Exorribonucleases , Complexos Multienzimáticos
9.
J Colloid Interface Sci ; 669: 952-964, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38759594

RESUMO

HYPOTHESIS: Magnetic particles are widely used in many adsorption and removal processes. Among the many types of magnetic colloids, magnetic Janus particles offer significant possibilities for the effective removal of several components from aqueous solutions. Nevertheless, the synthesis of structures integrating different types of materials requires scalable fabrication processes to overcome the limitations of the available methodologies. Herein, we hypothesized a fabrication process for dual-surface functionalized magnetic Janus particles. EXPERIMENTS: The primary silica particles with surface-attached amine groups are further asymmetrically modified by iron oxide nanoparticles, exploiting Pickering emulsion and electroless deposition techniques. The dual surface functionality of the particles is designed for its versatility and demonstrated in two wastewater-related applications. FINDINGS: We show that our design can simultaneously remove chromium (VI) and phenol from aqueous solution. The fabricated magnetic-responsive Janus particles are also an effective adsorbent for genomic Deoxyribonucleic acid (DNA) and show superior performance to commercial magnetic beads. Thus, this study provides a novel platform for designing magnetic Janus particles with multifunctional surfaces for wastewater treatment applications.

11.
Biomater Adv ; 161: 213885, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38743993

RESUMO

Essential organs, such as the heart and liver, contain a unique porous network that allows oxygen and nutrients to be exchanged, with distinct random to ordered regions displaying varying degrees of strength. A novel technique, referred to here as flow-induced lithography, was developed. This technique generates tunable anisotropic three-dimensional (3D) structures. The ink for this bioprinting technique was made of titanium dioxide nanorods (Ti) and kaolinite nanoclay (KLT) dispersed in a GelMA/PEGDA polymeric suspension. By controlling the flow rate, aligned particle microstructures were achieved in the suspensions. The application of UV light to trigger the polymerization of the photoactive prepolymer freezes the oriented particles in the polymer network. Because the viability test was successful in shearing suspensions containing cells, the flow-induced lithography technique can be used with both acellular scaffolds and cell-laden structures. Fabricated hydrogels show outstanding mechanical properties resembling human tissues, as well as significant cell viability (> 95 %) over one week. As a result of this technique and the introduction of bio-ink, a novel approach has been pioneered for developing anisotropic tissue implants utilizing low-viscosity biomaterials.


Assuntos
Hidrogéis , Impressão Tridimensional , Estereolitografia , Alicerces Teciduais , Hidrogéis/química , Alicerces Teciduais/química , Anisotropia , Humanos , Titânio/química , Engenharia Tecidual/métodos , Sobrevivência Celular , Bioimpressão/métodos
12.
Int J Cardiol ; 410: 132179, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38761972

RESUMO

BACKGROUND: Optimal strategies to manage embolization of transcatheter aortic valve implantation (TAVI) devices are unclear; valve-in-valve (ViV) is often used. We aimed to describe through one-single center experience its rate, causes, consequences, and management as well as the rate and relevance of commissural alignment (CA) in this context. METHODS: We identified across 1038 TAVI cases, those cases requiring ViV for the management of first device embolization. CA (absence or mild misalignment) after first and second device was assessed by CT or fluoroscopy. RESULTS: A total of 23 cases (2.2%) were identified, 52.3% embolized towards the aorta and 47.7% towards the ventricle. Suboptimal implant height (38%) and embolization at the time of post-dilation (23%) were the most frequent mechanisms together with greater rate of bicuspid valve (p < 0.001) and a trend to greater annular eccentricity. Procedural and 1-year death occurred in 13% and 34%, respectively (vs. 1.1% and 7.8% in the global cohort, p < 0.001). CA was present in 76.9% of the prostheses initially implanted but was only spontaneously achieved in 30.8% of the second ViV device. Adequate CA of both prostheses was identified in only two cases (8.7%). There were no cases of coronary obstruction. CONCLUSIONS: TAVI device embolization mechanisms can often be predicted and prevented. Mortality following bail-out ViV is higher than in regular TAVI procedures but 2/3 of these patients survived beyond 1-year follow-up. In them, valve degeneration or coronary re-access might be particularly challenging since CA was rarely achieved with both devices suggesting that greater efforts should be made in this regard.


Assuntos
Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/métodos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Resultado do Tratamento , Estenose da Valva Aórtica/cirurgia , Estudos Retrospectivos , Seguimentos , Desenho de Prótese , Embolia/etiologia , Valva Aórtica/cirurgia , Valva Aórtica/diagnóstico por imagem
13.
Nat Commun ; 15(1): 2915, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575645

RESUMO

Band engineering stands as an efficient route to induce strongly correlated quantum many-body phenomena. Besides inspiring analogies among diverse physical fields, tuning on demand the group velocity is highly attractive in photonics because it allows unconventional flows of light. Λ-schemes offer a route to control the propagation of light in a lattice-free configurations, enabling exotic phases such as slow-light and allowing for highly optical non-linear systems. Here, we realize room-temperature intercavity Frenkel polaritons excited across two strongly coupled cavities. We demonstrate the formation of a tuneable heavy-polariton, akin to slow light, appearing in the absence of a periodic in-plane potential. Our photonic architecture based on a simple three-level scheme enables the unique spatial segregation of photons and excitons in different cavities and maintains a balanced degree of mixing between them. This unveils a dynamical competition between many-body scattering processes and the underlying polariton nature which leads to an increased fluorescence lifetime. The intercavity polariton features are further revealed under appropriate resonant pumping, where we observe suppression of the polariton fluorescence intensity.

14.
Front Med (Lausanne) ; 11: 1325478, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660418

RESUMO

Introduction: COVID-19 vaccines are generally safe and effective; however, they are associated with various vaccine-induced cutaneous side effects. Several reported cases of primary cutaneous lymphomas (CLs) following the COVID-19 vaccination have raised concerns about a possible association. This systematic review aims to investigate and elucidate the potential link between CLs and SARS-CoV-2 vaccines. Methods: We performed a systematic literature search on PubMed, EBSCO and Scopus from January 01, 2019, to March 01, 2023, and analyzed studies based on determined eligibility criteria. The systematic review was performed based on the PRISMA protocol. Results: A total of 12 articles (encompassing 24 patients) were included in this analysis. The majority of CLs were indolent cutaneous T-cell lymphomas (CTCLs) (66,7%; 16/24), with Lymphomatoid papulosis (LyP) being the most common type (33,3%; 8/24). Most patients (79,2%; 19/24) developed lesions after receiving the COVID-19 mRNA-based vaccines, and predominantly after the first immunization dose (54,2%; 13/24). The presented CLs cases exhibited a tendency to exacerbate following subsequent COVID-19 vaccinations. Nevertheless, CLs were characterized by a favorable course, leading to remission in most cases. Conclusion: The available literature suggests an association between the occurrence and exacerbation of CLs with immune stimulation following COVID-19 vaccination. We hypothesize that post-vaccine CLs result from an interplay between cytokines and disrupted signaling pathways triggered by vaccine components, concurrently playing a pivotal role in the pathomechanism of CLs. However, establishing a definitive causal relationship between these events is currently challenging, primarily due to the relatively low rate of reported post-vaccine CLs. Nonetheless, these cases should not be disregarded, and patients with a history of lymphoproliferative disorders require post-COVID-19 vaccination monitoring to control the disease's course.Systematic review registrationwww.researchregistry.com, identifier [1723].

15.
Mayo Clin Proc ; 99(3): 400-410, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38432746

RESUMO

OBJECTIVE: To describe the evolution of symptoms in patients with symptomatic severe aortic stenosis (sSAS) undergoing valve replacement, the predictors of the persistence of these symptoms, and their prognostic significance. The evolution of symptoms after intervention in sSAS and their association with outcome are unknown. PATIENTS AND METHODS: Data from patients with sSAS who underwent intervention were collected. All-cause mortality and cardiovascular mortality were considered events. The evolution of symptoms and their association with events were studied. RESULTS: In this study, 451 consecutive patients with sSAS and no other valvular or coronary disease who were alive 30 days after intervention were included. Before valve replacement, 133 of the 451 patients (29.5%) had congestive heart failure requiring hospitalization. Of the remaining 318 patients, 287 (90.2%) had dyspnea on effort, 129 (40.6%) had angina, and 59 had syncope (18.6%). Symptoms disappeared after intervention in 192 of the 451 patients (42.6%) and remained in 259 (57.4%): 193 dyspnea, 9 angina, 17 syncope, and 60 admission for heart failure. Syncope on effort persisted in 4 of 33 patients (12.1%) and at rest in 11 of 20 (55.0%; P<.001). Age, body mass index, previous admission for heart failure, and chronic obstructive pulmonary disease were independently related to persistence of symptoms. Over a median follow-up of 56 months in our cohort of 451 patients, 129 deaths were registered (28.6%), 40 of which were cardiovascular (8.9%). Age, chronic obstructive pulmonary disease, chronic kidney disease, atrial fibrillation, heart failure, and persistence of symptoms were independently associated with all-cause mortality. CONCLUSION: Symptoms attributed to SAS remain after intervention in a high proportion of patients, particularly dyspnea on effort and syncope at rest. The persistence of symptoms after intervention identifies patients with poor outcome.


Assuntos
Estenose da Valva Aórtica , Insuficiência Cardíaca , Doença Pulmonar Obstrutiva Crônica , Humanos , Prognóstico , Síncope , Constrição Patológica , Dispneia/etiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Medidas de Resultados Relatados pelo Paciente , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia
16.
J Clin Med ; 13(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38542014

RESUMO

Background: The umbilicus is a fibrous remnant located in the centre of the abdomen. Various entities may be encountered in this special anatomical location; however, little is known about their dermoscopic presentation. The aim of this study was to provide a comprehensive summary of existing evidence on dermoscopic features of umbilical lesions. Methods: Studies assessing dermoscopic images of umbilical lesions were included in this study. No age, ethnicity or skin phototype restrictions were applied. Papers assessing lesions outside of the umbilical area, lacking dermoscopic images and/or dermoscopic description and not related to the topic were excluded. Embase, Medline and Cochrane Library were searched from inception to the end of May 2023. The Joanna Briggs Institute critical appraisal tools were used to evaluate the risk of bias of the selected studies. The quality and the level of evidence of included studies were assessed according to the Oxford 2011 Levels of Evidence. Thirty-four studies reporting a total of 39 lesions met the inclusion criteria and were included in qualitative analysis. Results: A qualitative synthesis of the following entities was performed: melanoma, nevi, basal cell carcinoma, fibroepithelioma of Pinkus, Sister Mary Joseph nodule, mycosis fungoides, dermatofibroma, endometriosis, epidermal cyst, granuloma, intravascular papillary endothelial hyperplasia, lichen planus, omphalolith, seborrheic keratosis, and syringoma. Conclusions: Dermoscopy is a non-invasive technique that may be useful in the differential diagnosis of umbilical lesions. The main limitations of this study were lack of a high level of evidence in the studies and the lack of uniformity in applied dermoscopic terminology between included studies.

17.
Cell Rep ; 43(3): 113931, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38492223

RESUMO

In adult mammals, injured retinal ganglion cells (RGCs) fail to spontaneously regrow severed axons, resulting in permanent visual deficits. Robust axon growth, however, is observed after intra-ocular injection of particulate ß-glucan isolated from yeast. Blood-borne myeloid cells rapidly respond to ß-glucan, releasing numerous pro-regenerative factors. Unfortunately, the pro-regenerative effects are undermined by retinal damage inflicted by an overactive immune system. Here, we demonstrate that protection of the inflamed vasculature promotes immune-mediated RGC regeneration. In the absence of microglia, leakiness of the blood-retina barrier increases, pro-inflammatory neutrophils are elevated, and RGC regeneration is reduced. Functional ablation of the complement receptor 3 (CD11b/integrin-αM), but not the complement components C1q-/- or C3-/-, reduces ocular inflammation, protects the blood-retina barrier, and enhances RGC regeneration. Selective targeting of neutrophils with anti-Ly6G does not increase axogenic neutrophils but protects the blood-retina barrier and enhances RGC regeneration. Together, these findings reveal that protection of the inflamed vasculature promotes neuronal regeneration.


Assuntos
Traumatismos do Nervo Óptico , beta-Glucanas , Animais , Neutrófilos , Regeneração Nervosa/fisiologia , Células Ganglionares da Retina/fisiologia , Axônios/fisiologia , Mamíferos
18.
Proc Natl Acad Sci U S A ; 121(11): e2309841121, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38442151

RESUMO

The transporter associated with antigen processing (TAP) is a key player in the major histocompatibility class I-restricted antigen presentation and an attractive target for immune evasion by viruses. Bovine herpesvirus 1 impairs TAP-dependent antigenic peptide transport through a two-pronged mechanism in which binding of the UL49.5 gene product to TAP both inhibits peptide transport and triggers its proteasomal degradation. How UL49.5 promotes TAP degradation has, so far, remained unknown. Here, we use high-content siRNA and genome-wide CRISPR-Cas9 screening to identify CLR2KLHDC3 as the E3 ligase responsible for UL49.5-triggered TAP disposal. We propose that the C terminus of UL49.5 mimics a C-end rule degron that recruits the E3 to TAP and engages the cullin-RING E3 ligase in endoplasmic reticulum-associated degradation.


Assuntos
Transportadores de Cassetes de Ligação de ATP , Degrons , Herpesviridae , Apresentação de Antígeno , Citomegalovirus , Degradação Associada com o Retículo Endoplasmático , Proteínas de Membrana Transportadoras , Peptídeos , Ubiquitina-Proteína Ligases/genética , Herpesviridae/fisiologia
19.
FASEB J ; 38(6): e23547, 2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38498368

RESUMO

Proteoglycan 4 (PRG4) is a boundary lubricant originally identified in articular cartilage and has been since shown to have immunomodulation and antifibrotic properties. Previously, we have demonstrated that recombinant human (rh)PRG4 treatment accelerates auricular cartilage injury closure through an inhibition of the fibrotic response, and promotion of tissue regeneration in mice. The purpose of the current study was to examine the effects of rhPRG4 treatment (vs. a DMSO carried control) on full-thickness skin wound healing in a preclinical porcine model. Our findings suggest that while rhPRG4 did not significantly accelerate nor impede full-thickness skin wound closure, it did improve repair quality by decreasing molecular markers of fibrosis and increasing re-vascularization. We also demonstrated that rhPRG4 treatment increased dermal adipose tissue during the healing process specifically by retaining adipocytes in the wound area but did not inhibit lipolysis. Overall, the results of the current study have demonstrated that rhPRG4 acts as antifibrotic agent and regulates dermal adipose tissue during the healing processes resulting in a tissue with a trajectory that more resembles the native skin vs. a fibrotic patch. This study provides strong rationale to examine if rhPRG4 can improve regeneration in human wounds.


Assuntos
Cartilagem Articular , Proteoglicanas , Suínos , Humanos , Animais , Camundongos , Proteoglicanas/farmacologia , Pele
20.
Microorganisms ; 12(3)2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38543658

RESUMO

Approximately a quarter of patients with infective endocarditis (IE) who have surgical indication only receive antibiotic treatment. Their short-term prognosis is dismal. We aimed to describe the characteristics of this group of patients to evaluate the mortality according to the cause of rejection and type of surgical indication and to analyze their prognostic factors of mortality. From 2005 to 2022, 1105 patients with definite left-sided IE were consecutively attended in three tertiary hospitals. Of them, 912 (82.5%) had formal surgical indication according to the most recent European Guidelines available in each period of the study and 303 (33%) only received medical treatment. These were older, had more comorbidities and higher in-hospital (46% vs. 24%; p < 0.001) and one year mortality (57.1% vs. 27.6%; p < 0.001) than operated patients. The main reason for surgical rejection was high surgical risk (57.1%) and the highest mortality when the cause were severe neurological conditions (76%). When the endocarditis team took the decision not to operate (25.5% of the patients), in-hospital (7%) and one-year mortality (17%) were low. In-hospital mortality associated with each surgical indication was 67% in heart failure, 53% in uncontrolled infection and 45% in prevention of embolisms (p < 0.001). Heart failure (OR: 2.26 CI95%: 1.29-3.96; p = 0.005), Staphylococcus aureus (OR: 3.17; CI95%: 1.72-5.86; p < 0.001) and persistent infection (OR: 5.07 CI95%: 2.85-9.03) are the independent risk factors of in-hospital mortality. One third of the patients with left-sided IE and formal surgical indication are rejected for surgery. In-hospital mortality is very high, especially when heart failure is the indication for surgery and when severe neurological conditions the reason for rejection. Short term prognosis of patients rejected by a specialized endocarditis team is favorable.

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