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1.
Ann Bot ; 2024 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-38908008

RESUMEN

BACKGROUND: The evolutionary success of flowering plants is associated with the vast diversity of their reproductive structures. Despite recent progress in understanding angiosperm-wide trends of floral structure and evolution, a synthetic view of the diversity in seed form and function across angiosperms is lacking. SCOPE: Here we present a roadmap to synthesise the diversity of seed forms in extant angiosperms, relying on the morphospace concept, i.e. a mathematical representation which relates multiple traits and describes the realised morphologies. We provide recommendations on how to broaden the range of measurable traits beyond mass, by using key morphological traits representative of the embryo, endosperm, and seed coat but also fruit attributes (e.g., dehiscence, fleshiness). These key traits were used to construct and analyse a morphospace to detect evolutionary trends and gain insight into how morphological traits relate to seed functions. Finally, we outline challenges and future research directions, combining the morphospace with macroevolutionary comparative methods to underline the drivers that gave rise to the diversity of observed seed forms. CONCLUSIONS: We conclude that this multidimensional approach has the potential, although still untapped, to improve our understanding of covariation among reproductive traits, and further elucidate angiosperm reproductive biology as a whole.

2.
Microbiol Resour Announc ; : e0024224, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38940606

RESUMEN

Sphingomonas sp. strain R1 was isolated from the stem of a tomato plant and exhibited antagonism with Agrobacterium. The complete genome sequence of this bacterium consists of one 3,874,532 bp circular chromosome and two plasmids.

3.
JACC Adv ; 3(4): 100909, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38939657

RESUMEN

Background: There is controversy regarding sex differences in short-term mortality in acute type A aortic dissection (ATAAD). Objectives: This study aimed to investigate the impact of sex differences on 30-day operative mortality after ATAAD surgery and to determine if other covariates modify the association. Methods: Consecutive patients (N = 5670) with surgically repaired ATAAD were identified from the multicenter China 5A study. The primary outcome was operative mortality. The age dependency was modeled using a cubic spline curve. Results: There were 1,503 females (26.5%) and 4,167 males (73.5%). Females were older and had a lower percentage of comorbidities compared with males. Females had higher mortality compared to males (10.2% vs 8.2%, P = 0.019); however, there was no difference after propensity analyses (adjusted OR: 1.334 [95% CI: 0.918-1.938]). There was an interaction with sex and age (P interaction = 0.035): older age was associated with higher odds of operative mortality among females (OR: 1.045 [95% CI: 1.029-1.061]) compared with males (OR: 1.025 [95% CI: 1.016-1.035]). The risk of mortality for males and females appears to diverge at 55 years of age (P interaction = 0.019): females under 55 years of age had similar odds to males (OR: 0.852 [95% CI: 0.603-1.205]) but higher odds when over 55 years (OR: 1.420 [95% CI: 1.096-1.839]) compared to males. Conclusions: Under the age of 55 years, females have similar odds of operative mortality compared with males; however, over the age of 55 years females have higher odds than males. Understanding differences in risk allows for individualized treatment strategies. (Additive Anti-inflammatory Action for Aortopathy & Arteriopathy; NCT04398992).

4.
Cancer Lett ; 592: 216929, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38697461

RESUMEN

Small cell lung cancer (SCLC) is a recalcitrant cancer characterized by high frequency loss-of-function mutations in tumor suppressors with a lack of targeted therapy due to absence of high frequency gain-of-function abnormalities in oncogenes. SMARCAL1 is a member of the ATP-dependent chromatin remodeling protein SNF2 family that plays critical roles in DNA damage repair and genome stability maintenance. Here, we showed that SMARCAL1 was overexpressed in SCLC patient samples and was inversely associated with overall survival of the patients. SMARCAL1 was required for SCLC cell proliferation and genome integrity. Mass spectrometry revealed that PAR6B was a downstream SMARCAL1 signal molecule which rescued inhibitory effects caused by silencing of SMARCAL1. By screening of 36 FDA-approved clinically available agents related to DNA damage repair, we found that an aza-anthracenedione, pixantrone, was a potent SMARCAL1 inhibitor which suppressed the expression of SMARCAL1 and PAR6B at protein level. Pixantrone caused DNA damage and exhibited inhibitory effects on SCLC cells in vitro and in a patient-derived xenograft mouse model. These results indicated that SMARCAL1 functions as an oncogene in SCLC, and pixantrone as a SMARCAL1 inhibitor bears therapeutic potentials in this deadly disease.


Asunto(s)
Proliferación Celular , ADN Helicasas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Animales , ADN Helicasas/genética , ADN Helicasas/metabolismo , Proliferación Celular/efectos de los fármacos , Ratones , Línea Celular Tumoral , Daño del ADN , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Reparación del ADN/efectos de los fármacos
5.
Small ; : e2401995, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38818678

RESUMEN

Upgrading thermosetting polymer waste and harvesting unwanted electromagnetic energy are of great significance in solving environmental pollution and energy shortage problems. Herein, inspired by the glass-blowing art, a spontaneous, controllable, and scalable strategy is proposed to prepare hollow carbon materials by inner blowing and outside blocking. Specifically, hierarchically neuron-like hollow carbon materials (HCMSs) with various sizes are fabricated from melamine-formaldehyde sponge (MS) waste. Benefiting from the synergistic of the hollow "cell body" and the connected "protrusions" networks, HCMSs reveal superior electromagnetic absorption performance with a strong reflection loss of -54.9 dB, electromagnetic-heat conversion ability with a high conversion efficiency of 34.4%, and efficient energy storage performance in supercapacitor. Furthermore, a multifunctional device integrating electromagnetic-heat-electrical energy conversion is designed, and its feasibility is proved by experiments and theoretical calculations. The integrated device reveals an output voltage of 34.5 mV and a maximum output power of 0.89 µW with electromagnetic radiation for 60 s. This work provides a novel solution to recycle polymer waste, electromagnetic energy, and unwanted thermal energy.

6.
Nature ; 629(8014): 1091-1099, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38750363

RESUMEN

The baobab trees (genus Adansonia) have attracted tremendous attention because of their striking shape and distinctive relationships with fauna1. These spectacular trees have also influenced human culture, inspiring innumerable arts, folklore and traditions. Here we sequenced genomes of all eight extant baobab species and argue that Madagascar should be considered the centre of origin for the extant lineages, a key issue in their evolutionary history2,3. Integrated genomic and ecological analyses revealed the reticulate evolution of baobabs, which eventually led to the species diversity seen today. Past population dynamics of Malagasy baobabs may have been influenced by both interspecific competition and the geological history of the island, especially changes in local sea levels. We propose that further attention should be paid to the conservation status of Malagasy baobabs, especially of Adansonia suarezensis and Adansonia grandidieri, and that intensive monitoring of populations of Adansonia za is required, given its propensity for negatively impacting the critically endangered Adansonia perrieri.


Asunto(s)
Adansonia , Filogenia , Adansonia/clasificación , Adansonia/genética , Biodiversidad , Conservación de los Recursos Naturales , Ecología , Especies en Peligro de Extinción , Evolución Molecular , Genoma de Planta/genética , Madagascar , Dinámica Poblacional , Elevación del Nivel del Mar
7.
Int J Surg ; 110(6): 3346-3356, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38445499

RESUMEN

BACKGROUND: Peripheral platelet-white blood cell ratio (PWR) integrating systemic inflammatory and coagulopathic pathways is a key residual inflammatory measurement in the management of acute DeBakey type I aortic dissection (AAD); however, trajectories of PWR in AAD is poorly defined. METHODS: Two AAD cohorts were included in two cardiovascular centers (2020-2022) if patients underwent emergency total arch replacement with frozen elephant trunk implantation. PWR data were collected over time at baseline and five consecutive days after surgery. Trajectory patterns of PWR were determined using the latent class mixed modelling (LCMM). Cox regression was used to determine independent risk factors. By adding PWR Trajectory, a user-friendly nomogram was developed for predicting mortality after surgery. RESULTS: Two hundred forty-six patients with AAD were included with a median follow-up of 26 (IRQ 20-37) months. Three trajectories of PWR were identified [cluster α 45(18.3%), ß105 (42.7%), and γ 96 (39.0%)]. Cluster γ was associated with higher risk of mortality at follow-up (crude HR, 3.763; 95% CI: 1.126-12.574; P =0.031) than cluster α. By the addition of PWR trajectories, an inflammatory nomogram, composed of age, hemoglobin, estimated glomerular filtration rate, and cardiopulmonary time was developed and internally validated, with adequate discrimination [the area under the receiver-operating characteristic curve 0.765, 95% CI: 0.660-0.869)], calibration, and clinical utility. CONCLUSION: Based on PWR trajectories, three distinct clusters were identified with short-term outcomes, and longitudinal residual inflammatory shed some light to individualize treatment strategies for AAD.


Asunto(s)
Disección Aórtica , Humanos , Disección Aórtica/cirugía , Disección Aórtica/mortalidad , Masculino , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Pronóstico , Anciano , Inflamación/sangre , Recuento de Leucocitos , Nomogramas , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/mortalidad , Factores de Riesgo
8.
Int J Cardiol Heart Vasc ; 50: 101341, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38313452

RESUMEN

Background: Early identification of patients at high risk of operative mortality is important for acute type A aortic dissection (TAAD). We aimed to investigate whether patients with distinct risk stratifications respond differently to anti-inflammatory pharmacotherapy. Methods: From 13 cardiovascular hospitals, 3110 surgically repaired TAAD patients were randomly divided into a training set (70%) and a test set (30%) to develop and validate a risk model to predict operative mortality using extreme gradient boosting. Performance was measured by the area under the receiver operating characteristic curve (AUC). Subgroup analyses were performed by risk stratifications (low versus middle-high risk) and anti-inflammatory pharmacotherapy (absence versus presence of ulinastatin use). Results: A simplified risk model was developed for predicting operative mortality, consisting of the top ten features of importance: platelet-leukocyte ratio, D-dimer, activated partial thromboplastin time, urea nitrogen, glucose, lactate, base excess, hemoglobin, albumin, and creatine kinase-MB, which displayed a superior discrimination ability (AUC: 0.943, 95 % CI 0.928-0.958 and 0.884, 95 % CI 0.836-0.932) in the derivation and validation cohorts, respectively. Ulinastatin use was not associated with decreased risk of operative mortality among each risk stratification, however, ulinastatin use was associated with a shorter mechanical ventilation duration among patients with middle-high risk (defined as risk probability >5.0 %) (ß -1.6 h, 95 % CI [-3.1, -0.1] hours; P = 0.048). Conclusion: This risk model reflecting inflammatory, coagulation, and metabolic pathways achieved acceptable predictive performances of operative mortality following TAAD surgery, which will contribute to individualized anti-inflammatory pharmacotherapy.

9.
BMC Cardiovasc Disord ; 24(1): 120, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38383323

RESUMEN

BACKGROUND: Acute aortic syndrome (AAS) is a life-threatening condition. Inflammation plays a key role in the pathogenesis, development and progression of AAS, and is associated with significant mortality and morbidity. Understanding the inflammatory responses and inflammation resolutions is essential for an appropriate management of AAS. METHOD: Thirty Chinese cardiovascular centers have collaborated to create a multicenter observational registry (named Chinese Additive Anti-inflammatory Action for Aortopathy & Arteriopathy [5A] registry), with consecutive enrollment of adult patients who underwent surgery for AAS that was started on Jan 1, 2016 and will be ended on December 31, 2040. Specially, the impact of inflammation and anti-inflammatory strategies on the early and late adverse events are investigated. Primary outcomes are severe systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), Sequential Organ Failure Assessment (SOFA) scores at 7 days following this current surgery. Secondary outcomes are SISR, 30-day mortality, operative mortality, hospital mortality, new-onset stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. DISCUSSION: The analysis of this multicenter registry will allow our better knowledge of the prognostic importance of preoperative inflammation and different anti-inflammatory strategies in adverse events after surgery for AAS. This registry is expected to provide insights into novel different inflammatory resolutions in management of AAS beyond conventional surgical repair. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04398992 (Initial Release: 05/19/2020).


Asunto(s)
Unidades de Cuidados Intensivos , Enfermedades Vasculares , Adulto , Humanos , Antiinflamatorios , China , Inflamación , Estudios Multicéntricos como Asunto , Sistema de Registros , Estudios Observacionales como Asunto
10.
New Phytol ; 241(2): 623-631, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37715492

RESUMEN

Information on seed persistence and seedling emergence from the soil seed bank is critical for understanding species coexistence and predicting community dynamics. However, quantifying seed persistence in the soil is challenging; thus, its association with other life-history traits is poorly known on a broad scale. Using germination phenology for 349 species in a 42-yr experiment, we quantified the persistence-emergence correlations and their associations with intrinsic regeneration traits using Bayesian phylogenetic multilevel models. We showed no trade-off between seed persistence and seedling emergence. Physically dormant seeds were more persistent but exhibited lower emergence than nondormant seeds. Monocarpic species had both higher persistence and emergence than polycarpic species. Seed mass posed a marginal proxy for persistence, while emergence almost doubled from the smallest to the largest seeds. This study challenges the traditional assumption and is the first demonstration of noncorrelation between persistence and emergence, probably owing to the complexity of regenerative strategies. Species with short persistence and low emergence would be the most vulnerable for in situ conservation. Our analyses of this unique, long-term dataset provide a strong incentive for further experimental studies and a rich data resource for future syntheses.


Asunto(s)
Germinación , Plantones , Teorema de Bayes , Filogenia , Semillas , Suelo
11.
Open Heart ; 10(2)2023 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-38070883

RESUMEN

OBJECTIVE: Cabrol shunt has been introduced for surgical repair of type A aortic dissection (TAAD) without robust evidence supporting its routine preventive use. METHODS: Adult patients with TAAD from China 5A study were included if surgically repaired between 2016 and 2022. Primary outcome was operative mortality according to Society of Thoracic Surgeons criterion. Overall, we compared clinical outcomes in patients with and without Cabrol shunt, and subgroup analysis were further examined between Cabrol shunt and outcome among patients with or without root replacement. RESULTS: 3283 patients were finally identified for analysis, with median age of 51 (IQR 41-59) years, 2389 men, and 2201 treated with Cabrol shunt technique. Cabrol shunt-treated patients were more severely ill before surgery than those without Cabrol shunt. Overall, the rate of operative mortality was 6.6% (146/2201 in Cabrol shunt group and 71/1082 in non-Cabrol shunt group), with no association between Cabrol shunt and operative mortality (OR 1.012 (95% CI 0.754 to 1.357); p=0.938). Stratified by root replacement, Cabrol shunt was associated with similar risk of operative mortality either in patients without root replacement (OR 1.054 (0.747 to 1.487); p=0.764) or in patients with root replacement (OR 1.194 (0.563 to 2.536); p=0.644) (P interaction=0.765). Results were similar in multiple sensitivity analysis. CONCLUSION: Cabrol shunt was not associated with either a greatly lowered or an increased risk of operative mortality, regardless of aortic root replacement. Our study did not support the use of Cabrol shunt as a routine preventive strategy in the treatment of TAAD. TRIAL REGISTRATION NUMBER: NCT04398992.


Asunto(s)
Disección Aórtica , Masculino , Adulto , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Aorta/cirugía , China
12.
Microbiol Spectr ; 11(6): e0147123, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-37905800

RESUMEN

IMPORTANCE: Of 123 identified isolates from the fruit surface, C. tropicalis was the most frequently found species, followed by Meyerozyma caribbica and Candida krusei. All three fluconazole-resistant C. tropicalis were non-susceptible to voriconazole and belonged to the same predominant genotype of azole-resistant C. tropicalis causing candidemia in patients in Taiwan. Our findings provide evidence that fruit should be washed before eaten not only to remove chemicals but also potential drug-resistant pathogenic microbes, especially for immunocompromised individuals. To keep precious treatment options in patients, we not only continuously implement antimicrobial stewardship in hospitals but also reducing/stopping the use of agricultural fungicide classes used in human medicine.


Asunto(s)
Antifúngicos , Candida tropicalis , Humanos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candida tropicalis/genética , Frutas , Fluconazol/farmacología , Voriconazol , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Fúngica
13.
J Cardiovasc Transl Res ; 16(6): 1383-1391, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37713048

RESUMEN

Association of distinct inflammatory profiles with short-term mortality is little known in type A aortic dissection (TAAD). Latent class analysis was used to identify distinct inflammatory profiles based on leukocyte, neutrophils, monocyte, lymphocytes, platelet, fibrinogen, D-dimer, neutrophils-lymphocyte ratio, platelet-lymphocyte ratio, and lymphocyte-monocyte ratio. We identified 193 patients with median age of 56 (IQR 47-63) years and 146 males. Patients were divided as hyper-inflammatory profiles (84 [43.5%]) and hypo-inflammatory profiles (109 [56.5%]). Although baseline characteristics were not different, hyper-inflammatory patients had higher 6-month mortality (20 [23.8%] vs. 11 [10.1%]; P = 0.014) and 30-day mortality (18 [21.4%] vs. 9 [8.3%], P = 0.009) than hypo-inflammatory patients. After adjustment for potential confounders, hyper-inflammatory profiles remain associated with higher risk of 6-month mortality than hypo-inflammatory profiles (adjusted OR 2.427 [95%CI 1.154, 5.105], P = 0.019). Assessment of preoperative inflammatory profiles adds clarity regarding the extent of inflammatory response to TAAD aetiopathologies, highlighting individual anti-inflammatory pharmacotherapy for TAAD. ClinicalTrials.gov Identifier: NCT04398992.


Asunto(s)
Disección Aórtica , Relevancia Clínica , Masculino , Humanos , Persona de Mediana Edad , Disección Aórtica/diagnóstico por imagen , Linfocitos , Fenotipo , Estudios Retrospectivos
16.
Cardiology ; 148(5): 448-456, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37429265

RESUMEN

INTRODUCTION: Knowledge is limited regarding the significance of pulmonary arterial pressure (PAP) in predominantly congenital mitral valve regurgitation (MR)-based intracardiac abnormalities. METHODS: From a prospective cohort, we included 200 patients with congenital MR regardless of other associated intracardiac abnormalities (mean age 60.4 months, 67% female, systolic PAP (sPAP) 54.2 mm Hg) surgically repaired in 2012-2019 and followed up to 2020 (median 30.0 months). Significant pulmonary hypertension (PH) was defined as sPAP >50 mm Hg at rest or mean PAP >25 mm Hg on right heart catheterization. By perioperative sPAP changes, patients were stratified as group I (pre-normotension to post-normotension), group II (pre-hypertension to post-normotension), or group III (pre-hypertension to post-hypertension). Primary outcomes were the recurrence of MR (defined as the regurgitation grade of moderate or greater) and the progression of MR (defined as any increase in the magnitude of regurgitation grade after surgery). Cox proportional hazard and Kaplan-Meier curve were performed. RESULTS: There was no association between preoperative PH and the recurrent MR (adjusted hazard ratios [aHR]: 1.146 [95% CI: 0.453-2.899]) and progressive MR (aHR: 1.753 [95% CI: 0.807-3.804]), respectively. There were no significant differences among group I, group II, and group III in the recurrent MR but in the progressive MR. A dose dependency was identified for preoperative sPAP with recurrent MR (aHR: 1.050 [95% CI: 1.029-1.071]) and progressive MR risks (aHR: 1.037 [95% CI: 1.019-1.055]), respectively. CONCLUSIONS: Preoperative higher sPAP is associated with worse outcomes, warranting heightened attention to the identification of perioperative sPAP.


Asunto(s)
Hipertensión Pulmonar , Insuficiencia de la Válvula Mitral , Prehipertensión , Humanos , Femenino , Preescolar , Masculino , Pronóstico , Presión Arterial , Estudios Prospectivos , Resultado del Tratamiento , Prehipertensión/complicaciones , Válvula Mitral/cirugía , Hipertensión Pulmonar/complicaciones , Estudios Retrospectivos
17.
Ecotoxicol Environ Saf ; 262: 115215, 2023 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-37421785

RESUMEN

Southwestern China has the largest geological phosphorus-rich mountain in the world, which is seriously degraded by mining activities. Understanding the trajectory of soil microbial recovery and identifying the driving factors behind such restoration, as well as conducting corresponding predictive simulations, can be instrumental in facilitating ecological rehabilitation. Here, high-throughput sequencing and machine learning-based approaches were employed to investigate restoration chronosequences under four restoration strategies (spontaneous re-vegetation with or without topsoil; artificial re-vegetation with or without the addition of topsoil) in one of the largest and oldest open-pit phosphate mines worldwide. Although soil phosphorus (P) is extremely high here (max = 68.3 mg/g), some phosphate solubilizing bacteria and mycorrhiza fungi remain as the predominant functional types. Soil stoichiometry ratios (C:P and N:P) closely relate to the bacterial variation, but soil P content contributes less to microbial dynamics. Meanwhile, as restoration age increases, denitrifying bacteria and mycorrhizal fungi significantly increased. Significantly, based on partial least squares path analysis, it was found that the restoration strategy is the primary factor that drives soil bacterial and fungal composition as well as functional types through both direct and indirect effects. These indirect effects arise from factors such as soil thickness, moisture, nutrient stoichiometry, pH, and plant composition. Moreover, its indirect effects constitute the main driving force towards microbial diversity and functional variation. Using a hierarchical Bayesian model, scenario analysis reveals that the recovery trajectories of soil microbes are contingent upon changes in restoration stage and treatment strategy; inappropriate plant allocation may impede the recovery of the soil microbial community. This study is helpful for understanding the dynamics of the restoration process in degraded phosphorus-rich ecosystems, and subsequently selecting more reasonable recovery strategies.

18.
Eur Heart J ; 44(29): 2746-2759, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37377116

RESUMEN

AIMS: The mechanisms underlying ageing-induced vascular remodelling remain unclear. This study investigates the role and underlying mechanisms of the cytoplasmic deacetylase sirtuin 2 (SIRT2) in ageing-induced vascular remodelling. METHODS AND RESULTS: Transcriptome and quantitative real-time PCR data were used to analyse sirtuin expression. Young and old wild-type and Sirt2 knockout mice were used to explore vascular function and pathological remodelling. RNA-seq, histochemical staining, and biochemical assays were used to evaluate the effects of Sirt2 knockout on the vascular transcriptome and pathological remodelling and explore the underlying biochemical mechanisms. Among the sirtuins, SIRT2 had the highest levels in human and mouse aortas. Sirtuin 2 activity was reduced in aged aortas, and loss of SIRT2 accelerated vascular ageing. In old mice, SIRT2 deficiency aggravated ageing-induced arterial stiffness and constriction-relaxation dysfunction, accompanied by aortic remodelling (thickened vascular medial layers, breakage of elastin fibres, collagen deposition, and inflammation). Transcriptome and biochemical analyses revealed that the ageing-controlling protein p66Shc and metabolism of mitochondrial reactive oxygen species (mROS) contributed to SIRT2 function in vascular ageing. Sirtuin 2 repressed p66Shc activation and mROS production by deacetylating p66Shc at lysine 81. Elimination of reactive oxygen species by MnTBAP repressed the SIRT2 deficiency-mediated aggravation of vascular remodelling and dysfunction in angiotensin II-challenged and aged mice. The SIRT2 coexpression module in aortas was reduced with ageing across species and was a significant predictor of age-related aortic diseases in humans. CONCLUSION: The deacetylase SIRT2 is a response to ageing that delays vascular ageing, and the cytoplasm-mitochondria axis (SIRT2-p66Shc-mROS) is important for vascular ageing. Therefore, SIRT2 may serve as a potential therapeutic target for vascular rejuvenation.


Asunto(s)
Sirtuina 2 , Remodelación Vascular , Ratones , Humanos , Animales , Anciano , Sirtuina 2/metabolismo , Proteína Transformadora 1 que Contiene Dominios de Homología 2 de Src , Especies Reactivas de Oxígeno/metabolismo , Envejecimiento , Ratones Noqueados
19.
Cell Rep Med ; 4(5): 101046, 2023 05 16.
Artículo en Inglés | MEDLINE | ID: mdl-37196632

RESUMEN

Swanton et al.1 find that PM2.5 exposure is associated with EGFR/KRAS-driven lung cancer incidence. PM2.5 increases EGFR pre-mutated alveolar type II cell progenitor function and tumorigenic activity through interstitial macrophage-secreted IL-1ß, providing potential prevention approaches to inhibit cancer initiation.


Asunto(s)
Contaminación del Aire , Neoplasias Pulmonares , Humanos , Material Particulado/efectos adversos , Contaminación del Aire/efectos adversos , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/genética , Receptores ErbB/genética , Mutación
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