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1.
Eur Heart J ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38953786

RESUMEN

BACKGROUND AND AIMS: Physical activity has proven effective in preventing atherosclerotic cardiovascular disease, but its role in preventing degenerative valvular heart disease (VHD) remains uncertain. This study aimed to explore the dose-response association between moderate to vigorous physical activity (MVPA) volume and the risk of degenerative VHD among middle-aged adults. METHODS: A full week of accelerometer-derived MVPA data from 87 248 UK Biobank participants (median age 63.3, female: 56.9%) between 2013 and 2015 were used for primary analysis. Questionnaire-derived MVPA data from 361 681 UK Biobank participants (median age 57.7, female: 52.7%) between 2006 and 2010 were used for secondary analysis. The primary outcome was the diagnosis of incident degenerative VHD, including aortic valve stenosis (AS), aortic valve regurgitation (AR), and mitral valve regurgitation (MR). The secondary outcome was VHD-related intervention or mortality. RESULTS: In the accelerometer-derived MVPA cohort, 555 incident AS, 201 incident AR, and 655 incident MR occurred during a median follow-up of 8.11 years. Increased MVPA volume showed a steady decline in AS risk and subsequent AS-related intervention or mortality risk, levelling off beyond approximately 300 min/week. In contrast, its association with AR or MR incidence was less apparent. The adjusted rates of AS incidence (95% confidence interval) across MVPA quartiles (Q1-Q4) were 11.60 (10.20, 13.20), 7.82 (6.63, 9.23), 5.74 (4.67, 7.08), and 5.91 (4.73, 7.39) per 10 000 person-years. The corresponding adjusted rates of AS-related intervention or mortality were 4.37 (3.52, 5.43), 2.81 (2.13, 3.71), 1.93 (1.36, 2.75), and 2.14 (1.50, 3.06) per 10 000 person-years, respectively. Aortic valve stenosis risk reduction was also observed with questionnaire-based MVPA data [adjusted absolute difference Q4 vs. Q1: AS incidence, -1.41 (-.67, -2.14) per 10 000 person-years; AS-related intervention or mortality, -.38 (-.04, -.88) per 10 000 person-years]. The beneficial association remained consistent in high-risk populations for AS, including patients with hypertension, obesity, dyslipidaemia, and chronic kidney disease. CONCLUSIONS: Higher MVPA volume was associated with a lower risk of developing AS and subsequent AS-related intervention or mortality. Future research needs to validate these findings in diverse populations with longer durations and repeated periods of activity monitoring.

2.
Can J Infect Dis Med Microbiol ; 2024: 4749097, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38826677

RESUMEN

Background: Blood safety levels have been significantly improved since the implementation of nucleic acid amplification technology (NAT) testing for blood donors. However, there remains a residual risk of transfusion transmission infections. This study aimed to evaluate the prevalence of HIV and its residual risk transmission among volunteer blood donors of Zhejiang Province, China, for five years after NAT implementation. Materials and Methods: All specimens and information were collected from voluntary unpaid donors at all blood services in Zhejiang Province, China, from January 2018 to December 2022. The HIV antibody or antigen and HIV RNA were detected using enzyme-linked immunosorbent assay and NAT, respectively. The HIV residual risk transmission was calculated using the incidence or window period model. Results: A total of 3,375,678 voluntary blood donors were detected, revealing an HIV prevalence of 9.92/100000. The HIV prevalence of blood donors in 12 blood services in Zhejiang Province was 6.11, 6.98, 7.45, 8.21, 8.36, 8.94, 9.04, 9.66, 9.73, 10.22, 11.80, and 12.47 per 100000 donors, without statistically significant difference observed among the services (p > 0.05). The HIV prevalence of males (15.49/100000) was significantly higher compared to females (1.95/100000; p < 0.05). There was an insignificant difference in HIV prevalence among blood donors of all different age groups (p > 0.05), but the HIV prevalence in the 26-35 age group and 18-25 age group was significantly higher compared to the 36-45 age group (p < 0.05). The difference in HIV prevalence between first-time blood donors (13.65/100,000) and repeat blood donors (6.78/100,000) was statistically significant (p < 0.05). From 2018 to 2022, the HIV residual risk in blood transfusion transmission was 0.266/100000. Conclusion: The prevalence of HIV among blood donors in Zhejiang Province, China, is associated with age, gender, and times of blood donation. The HIV residual risk in blood transfusion transmission remains low in the province, and increasing the rate of repeat blood donors is beneficial to improve blood safety.

3.
J Mol Cell Cardiol ; 194: 16-31, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38821243

RESUMEN

BACKGROUND: Hypoxia-induced pulmonary artery hypertension (HPH) is a complication of chronic hypoxic lung disease and the third most common type of pulmonary artery hypertension (PAH). Epigenetic mechanisms play essential roles in the pathogenesis of HPH. N6-methyladenosine (m6A) is an important modified RNA nucleotide involved in a variety of biological processes and an important regulator of epigenetic processes. To date, the precise role of m6A and regulatory molecules in HPH remains unclear. METHODS: HPH model and pulmonary artery smooth muscle cells (PASMCs) were constructed from which m6A changes were observed and screened for AlkB homolog 5 (Alkbh5). Alkbh5 knock-in (KI) and knock-out (KO) mice were constructed to observe the effects on m6A and evaluate right ventricular systolic pressure (RVSP), left ventricular and septal weight [RV/(LV + S)], and pulmonary vascular remodeling in the context of HPH. Additionally, the effects of Alkbh5 knockdown using adenovirus were examined in vitro on m6A, specifically in PASMCs with regard to proliferation, migration and cytochrome P450 1A1 (Cyp1a1) mRNA stability. RESULTS: In both HPH mice lung tissues and hypoxic PASMCs, a decrease in m6A was observed, accompanied by a significant up-regulation of Alkbh5 expression. Loss of Alkbh5 attenuated the proliferation and migration of hypoxic PASMCs in vitro, with an associated increase in m6A modification. Furthermore, Alkbh5 KO mice exhibited reduced RVSP, RV/(LV + S), and attenuated vascular remodeling in HPH mice. Mechanistically, loss of Alkbh5 inhibited Cyp1a1 mRNA decay and increased its expression through an m6A-dependent post-transcriptional mechanism, which hindered the proliferation and migration of hypoxic PASMCs. CONCLUSION: The current study highlights the loss of Alkbh5 impedes the proliferation and migration of PASMCs by inhibiting post-transcriptional Cyp1a1 mRNA decay in an m6A-dependent manner.

4.
J Cell Biol ; 223(8)2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-38713825

RESUMEN

Whether, to what extent, and how the axons in the central nervous system (CNS) can withstand sudden mechanical impacts remain unclear. By using a microfluidic device to apply controlled transverse mechanical stress to axons, we determined the stress levels that most axons can withstand and explored their instant responses at nanoscale resolution. We found mild stress triggers a highly reversible, rapid axon beading response, driven by actomyosin-II-dependent dynamic diameter modulations. This mechanism contributes to hindering the long-range spread of stress-induced Ca2+ elevations into non-stressed neuronal regions. Through pharmacological and molecular manipulations in vitro, we found that actomyosin-II inactivation diminishes the reversible beading process, fostering progressive Ca2+ spreading and thereby increasing acute axonal degeneration in stressed axons. Conversely, upregulating actomyosin-II activity prevents the progression of initial injury, protecting stressed axons from acute degeneration both in vitro and in vivo. Our study unveils the periodic actomyosin-II in axon shafts cortex as a novel protective mechanism, shielding neurons from detrimental effects caused by mechanical stress.


Asunto(s)
Actomiosina , Axones , Estrés Mecánico , Animales , Ratones , Actomiosina/metabolismo , Axones/metabolismo , Axones/patología , Calcio/metabolismo , Células Cultivadas , Degeneración Nerviosa/patología , Ratas
5.
Cereb Cortex ; 34(5)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38700440

RESUMEN

While the auditory and visual systems each provide distinct information to our brain, they also work together to process and prioritize input to address ever-changing conditions. Previous studies highlighted the trade-off between auditory change detection and visual selective attention; however, the relationship between them is still unclear. Here, we recorded electroencephalography signals from 106 healthy adults in three experiments. Our findings revealed a positive correlation at the population level between the amplitudes of event-related potential indices associated with auditory change detection (mismatch negativity) and visual selective attention (posterior contralateral N2) when elicited in separate tasks. This correlation persisted even when participants performed a visual task while disregarding simultaneous auditory stimuli. Interestingly, as visual attention demand increased, participants whose posterior contralateral N2 amplitude increased the most exhibited the largest reduction in mismatch negativity, suggesting a within-subject trade-off between the two processes. Taken together, our results suggest an intimate relationship and potential shared mechanism between auditory change detection and visual selective attention. We liken this to a total capacity limit that varies between individuals, which could drive correlated individual differences in auditory change detection and visual selective attention, and also within-subject competition between the two, with task-based modulation of visual attention causing within-participant decrease in auditory change detection sensitivity.


Asunto(s)
Atención , Percepción Auditiva , Electroencefalografía , Percepción Visual , Humanos , Atención/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Percepción Auditiva/fisiología , Percepción Visual/fisiología , Estimulación Acústica/métodos , Estimulación Luminosa/métodos , Potenciales Evocados/fisiología , Encéfalo/fisiología , Adolescente
6.
Acta Cardiol ; 79(2): 149-158, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38628089

RESUMEN

BACKGROUND: This study aims to investigate prognostic implications of coronary slow flow (CSF) and angiography-derived index of microcirculatory resistance (caIMR) in patients with angina and normal coronary arteries. METHODS: A total of 582 patients were enrolled with angiographically normal coronary arteries. caIMR was calculated using a commercial software. Patients were followed up for a median of 45 months. The primary endpoint was defined as major adverse cardiovascular events (MACEs) comprising death, myocardial infarction and readmission for angina or heart failure. RESULTS: CSF was diagnosed when TIMI grade 2 flow presented in at least one coronary artery. Multivariate analysis indicated TIMI-flow-based determination of CSF was not significantly associated with MACEs [hazard ratio (HR): 2.14; 95% confidence interval (CI): 0.87-5.31; p = 0.099), while caIMR >42 (HR: 2.53; 95% CI: 1.02-6.32; p = 0.047) were independent predictors of MACEs. Incorporation of caIMR improved the area under the curve from 0.587 to 0.642. CONCLUSIONS: caIMR was an independent prognostic factor of long-term cardiovascular events in patients with CSF. Evaluation of caIMR improved the risk stratification of patients with angiographically-normal coronary arteries.


Asunto(s)
Enfermedad de la Arteria Coronaria , Vasos Coronarios , Humanos , Pronóstico , Vasos Coronarios/diagnóstico por imagen , Angiografía Coronaria , Estudios Retrospectivos , Microcirculación , Angina de Pecho/diagnóstico
7.
iScience ; 27(4): 109368, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38510112

RESUMEN

Focusing attention in visual working memory (vWM) depends on the ability to filter distractors and expand the scope of targets. Although many properties of attention processes in vWM have been well documented, it remains unclear how the mechanisms of neurovascular coupling (NVC) function during attention processes in vWM. Here, we show simultaneous multimodal data that reveal the similar temporal and spatial features of attention processes during vWM. These similarities lead to common NVC outcomes across individuals. When filtering out distractors, the electroencephalography (EEG)-informed NVC displayed broader engagement across the frontoparietal network. A negative correlation may exist between behavioral metrics and EEG-informed NVC strength related to attention control. On a dynamic basis, NVC features exhibited higher discriminatory power in predicting behavior than other features alone. These results underscore how multimodal approaches can advance our understanding of the role of attention in vWM, and how NVC fluctuations are associated with actual behavior.

8.
Anal Bioanal Chem ; 416(7): 1561-1570, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38285227

RESUMEN

The abuse of herbicides has emerged as a great threat to food security. Herein, a low-background interference detection method based on UPLC-MS was developed for the simultaneous determination of glufosinate, glyphosate, and its metabolite aminomethylphosphonic acid (AMPA) in foods. Initially, this study proposed a simple and rapid pretreatment method, utilizing water extraction and PRiME HLB purification to isolate glyphosate, glufosinate, and AMPA from food samples. After the optimization of pretreatment conditions, the processed samples are then analyzed directly by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) without pre-column derivatization. The method can effectively reduce interference from by-products of pre-column derivatization and background substrates of food sample, showing low matrix effects (ME) ranging from - 24.83 to 32.10%. Subsequently, the method has been validated by 13 kinds of food samples. The recoveries of the three herbicides in the food samples range from 84.2 to 115.6%. The limit of detection (LOD) is lower to 0.073 mg/kg, 0.017 mg/kg, and 0.037 mg/kg, respectively. Moreover, the method shows an excellent reproducibility with relative standard deviations (RSD) within 16.9%. Thus, the method can provide high trueness, reproducibility, sensitivity, and interference-free detection to ensure human health safety.


Asunto(s)
Aminobutiratos , Glifosato , Herbicidas , Organofosfonatos , Humanos , Cromatografía Liquida/métodos , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico , Glicina , Cromatografía Líquida con Espectrometría de Masas , Espectrometría de Masas en Tándem/métodos , Reproducibilidad de los Resultados , Herbicidas/análisis , Cromatografía Líquida de Alta Presión
9.
Cell Biosci ; 13(1): 197, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37915043

RESUMEN

Organoids, three-dimensional structures cultured in vitro, can recapitulate the microenvironment, complex architecture, and cellular functions of in vivo organs or tissues. In recent decades, liver organoids have been developed rapidly, and their applications in biomedicine, such as drug screening, disease modeling, and regenerative medicine, have been widely recognized. However, the lack of repeatability and consistency, including the lack of standardized culture conditions, has been a major obstacle to the development and clinical application of liver organoids. It is time-consuming for researchers to identify an appropriate medium component scheme, and the usage of some ingredients remains controversial. In this review, we summarized and compared different methods for liver organoid cultivation that have been published in recent years, focusing on controversial medium components and discussing their advantages and drawbacks. We aimed to provide an effective reference for the development and standardization of liver organoid cultivation.

10.
Signal Transduct Target Ther ; 8(1): 431, 2023 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-37981648

RESUMEN

Hypoxia, characterized by reduced oxygen concentration, is a significant stressor that affects the survival of aerobic species and plays a prominent role in cardiovascular diseases. From the research history and milestone events related to hypoxia in cardiovascular development and diseases, The "hypoxia-inducible factors (HIFs) switch" can be observed from both temporal and spatial perspectives, encompassing the occurrence and progression of hypoxia (gradual decline in oxygen concentration), the acute and chronic manifestations of hypoxia, and the geographical characteristics of hypoxia (natural selection at high altitudes). Furthermore, hypoxia signaling pathways are associated with natural rhythms, such as diurnal and hibernation processes. In addition to innate factors and natural selection, it has been found that epigenetics, as a postnatal factor, profoundly influences the hypoxic response and progression within the cardiovascular system. Within this intricate process, interactions between different tissues and organs within the cardiovascular system and other systems in the context of hypoxia signaling pathways have been established. Thus, it is the time to summarize and to construct a multi-level regulatory framework of hypoxia signaling and mechanisms in cardiovascular diseases for developing more therapeutic targets and make reasonable advancements in clinical research, including FDA-approved drugs and ongoing clinical trials, to guide future clinical practice in the field of hypoxia signaling in cardiovascular diseases.


Asunto(s)
Enfermedades Cardiovasculares , Sistema Cardiovascular , Humanos , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/terapia , Hipoxia/genética , Oxígeno , Epigénesis Genética
11.
Catheter Cardiovasc Interv ; 102(7): 1210-1221, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37870101

RESUMEN

BACKGROUND: The predictors of success of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) through antegrade dissection and re-entry (ADR) using the Stingray system (Stingray ADR) remain elusive, mainly owing to the lack of consecutive angiographic and procedural records of patients. OBJECTIVES: This study aimed to identify indicators that can determine the success of CTO PCI performed using the Stingray ADR technique. METHODS: The clinical data of 115 patients who underwent CTO PCI through Stingray ADR at the same cardiac center were retrospectively and consecutively collected. Multivariate logistic regression analysis was performed to investigate the indicators of the success of ADR attempts. RESULTS: The technical success rate of Stingray ADR in CTO PCI was 72.2%. The overall technical success rate of CTO recanalization was 78.3% in all CTO PCIs having used Stingray Low Profile balloon. Vessel calcification (odds ratio [OR]: 4.03; 95% confidence interval [CI]: 1.49-11.88; p = 0.008), and retrograde puncture indicator (OR: 4.89; 95% CI: 1.51-17.11; p = 0.009) were identified as independent positive predictors. Blunt/no stump proximal to the occlusion segment (OR: 0.22; 95% CI: 0.06-0.64; p = 0.009), decision time before Stingray ADR (per 1 h increase) (OR: 0.54; 95% CI: 0.31-0.92; p = 0.026), operation duration of Stingray ADR (per 10 min increase) (OR: 0.62; 95% CI: 0.40-0.94; p = 0.028), and puncture site at the intraplaque region (OR: 0.24; 95% CI: 0.06-0.84; p = 0.026) were identified as the four negative independent predictors. CONCLUSIONS: This study revealed independent predictors of the success of CTO PCI performed using the Stingray ADR technique. As for CTO characteristics, the presence of calcification in the CTO segment and a tapered stump proximal to the lesion site can facilitate successful Stingray ADR. As for the procedures, the success rate of Stingray ADR can be improved by initiating the technique decisively and promptly, operating the system quickly and accurately and creating a puncture in the distal cap region of CTO under retrograde guidance.


Asunto(s)
Oclusión Coronaria , Intervención Coronaria Percutánea , Rajidae , Humanos , Animales , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Estudios Retrospectivos , Resultado del Tratamiento , Oclusión Coronaria/terapia , Oclusión Coronaria/cirugía , Angiografía Coronaria , Enfermedad Crónica , Factores de Riesgo , Sistema de Registros
12.
Artículo en Inglés | MEDLINE | ID: mdl-37674012

RESUMEN

BACKGROUND: Rapid development in coronary chronic total occlusion (CTO) interventional techniques and devices have achieved a greater success rate with favorable outcomes. Antegrade dissection re-entry (ADR) technique is an important CTO crossing strategy and a desirable approach for long CTOs with good distal landing zone. However, unsuccessful procedures in contemporary CTO-percutaneous coronary intervention (PCI) remain, especially in lesions with non-interventional collaterals. METHOD: Based on a single center experience, a hybrid interventional algorithm, parallel wire-based ADR (PW-ADR) combines the advantages of parallel wire technique (PWT) and device-based ADR to target CTO lesions with failed retrograde approach. A retrospective analysis of patients who underwent PW-ADR was performed. A risk nomogram was created to identify patients at high risk for technical failure. RESULTS: A total of 57 patients treated with PW-ADR were ultimately included in the present study. A total of 46 (80.7%) cases achieved technical success and procedural success, with low incidence of in-hospital complications or 1-year major adverse cardiac events (MACE). The risk nomogram identified 3 predictor variables associated with technical failure of PW-ADR, including tortuous vessel, J-CTO score, and times of antegrade coronary angiography (CAG) during ADR, with promising accuracy (AUROC 0.947). CONCLUSION: The novel hybrid CTO-PCI algorithm, PW-ADR, provided an alternative interventional approach for complex CTO lesions with a promising success rate. The risk nomogram served as a prompter for high-risk cases, which may warrant a change in treatment strategy.


The present study reported a new hybrid-PCI strategy with a promising success rate for the treatment of CTO from a single center experience, over last 5 years. A retrospective analysis of patients who underwent PW-ADR was performed. A risk nomogram was created to identify patients at high risk for technical failure. 80.7% of patients treated with PW-ADR were achieved technical success and procedural success, with low incidence of in-hospital complications or 1-year MACE in the present study. A total of 3 predictor variables were identified to be associated with technical failure of PW-ADR, including tortuous vessel, J-CTO score, and times of antegrade CAG during ADR. This prediction tool may allow early identification of more complex and difficult CTO cases that require a timely switch in strategic approach or termination of the procedure to avoid unnecessary surgical risk.

13.
Innovation (Camb) ; 4(5): 100489, 2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37636277

RESUMEN

It is essential to create a sustainable and all-encompassing panvascular ecosystem that integrates medical care, industry-academia research, prevention, and management, necessitating the in-depth participation of every cardiovascular doctor on their journey of unwavering excellence. "From doctors, by researchers/engineers, for patients" is the foundation of sustainable development in the "panvascular medicine +" ecosystem. Medical education can make knowledge tangible and serve as a conduit for inheritance and innovation. Prevention covers intelligent decision-making, primary prevention, and the popularization of knowledge. Furthermore, management is a potent tool for promoting development through overall coordination with social governance. Thus, in the "panvascular medicine +" ecosystem, cardiovascular doctors need to prioritize the doctor-patient collaboration, serving patients while possessing capabilities in scientific research, engineering applications, education, prevention, and management. This enables them to promote comprehensive and lifelong health management for patients.

14.
J Multidiscip Healthc ; 16: 2463-2470, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37649873

RESUMEN

Background: The tip-in technique, which involves advancing an antegrade microcatheter cross the lesion over a retrograde guidewire, is an elaborated maneuver in the recanalization of coronary chronic total occlusion (CTO). We seek to assess the efficiency of a guide extension catheter-facilitated tip-in technique in comparison to the traditional retrograde approach, which is accomplished by an externalization wire. Methods: Thirty-three CTO patients successfully revascularized using guide extension catheter-facilitated "tip-in" were included and matched with another 33 patients by J-CTO score and operators, whose CTO was recanalized using an externalized wire. The manipulation time from the first retrograde wire entering the antegrade guide to the first antegrade balloon inflation in the occlusion was calculated. Results: Compared with the wire-externalization group, the manipulation time in the tip-in group was significantly shortened [389s; interquartile range (IQR), 272-478 vs 706s; IQR, 560-914; p < 0.001]. There was a trend in decreasing total operation time and radiation dose, but it did not reach statistical significance. Conclusion: Guide extension catheter-facilitated tip-in is an efficient method to achieve the recanalization of CTO in a retrograde way, which would be pivotal when the retrograde microcatheter could not be advanced into the antegrade guide catheter.

15.
Sci Bull (Beijing) ; 68(17): 1954-1974, 2023 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-37541793

RESUMEN

As an emerging discipline, panvascular diseases are a set of vascular diseases with atherosclerosis as the common pathogenic hallmark, which mostly affect vital organs like the heart, brain, kidney, and limbs. As the major responser to the most common stressor in the vasculature (hypoxia)-hypoxia-inducible factors (HIFs), and the primary regulator of pressure and oxygen delivery in the vasculature-vascular smooth muscle cells (VSMCs), their own multifaceted nature and their interactions with each other are fascinating. Abnormally active VSMCs (e.g., atherosclerosis, pulmonary hypertension) or abnormally dysfunctional VSMCs (e.g., aneurysms, vascular calcification) are associated with HIFs. These widespread systemic diseases also reflect the interdisciplinary nature of panvascular medicine. Moreover, given the comparable proliferative characteristics exhibited by VSMCs and cancer cells, and the delicate equilibrium between angiogenesis and cancer progression, there is a pressing need for more accurate modulation targets or combination approaches to bolster the effectiveness of HIF targeting therapies. Based on the aforementioned content, this review primarily focused on the significance of integrating the overall and local perspectives, as well as temporal and spatial balance, in the context of the HIF signaling pathway in VSMC-related panvascular diseases. Furthermore, the review discussed the implications of HIF-targeting drugs on panvascular disorders, while considering the trade-offs involved.


Asunto(s)
Calcificación Vascular , Enfermedades Vasculares , Humanos , Músculo Liso Vascular/metabolismo , Hipoxia/metabolismo , Enfermedades Vasculares/metabolismo , Calcificación Vascular/metabolismo , Transducción de Señal
16.
Clin Transl Med ; 13(8): e1377, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37598403

RESUMEN

BACKGROUND: SIRT6, an important NAD+ -dependent protein, protects endothelial cells from inflammatory and oxidative stress injuries. However, the role of SIRT6 in cardiac microvascular endothelial cells (CMECs) under ischemia-reperfusion injury (IRI) remains unclear. METHODS: The HUVECs model of oxygen-glucose deprivation/reperfusion (OGD/R) was established to simulate the endothelial IRI in vitro. Endoplasmic reticulum oxidase 1 alpha (Ero1α) mRNA and protein levels in SIRT6-overexpressing or SIRT6-knockdown cells were measured by qPCR and Western blotting. The levels of H2 O2 and mitochondrial reactive oxygen species (ROS) were detected to evaluate the status of oxidative stress. The effects of SIRT6 deficiency and Ero1α knockdown on cellular endoplasmic reticulum stress (ERS), inflammation, apoptosis and barrier function were detected by a series of molecular biological experiments and functional experiments in vitro. Chromatin immunoprecipitation, Western blotting, qPCR, and site-specific mutation experiments were used to examine the underlying molecular mechanisms. Furthermore, endothelial cell-specific Sirt6 knockout (ecSirt6-/- ) mice were subjected to cardiac ischemia-reperfusion surgery to investigate the effects of SIRT6 in CMECs in vivo. RESULTS: The expression of Ero1α was significantly upregulated in SIRT6-knockdown endothelial cells, and high Ero1α expression correlated with the accumulation of H2 O2 and mitochondrial ROS. In addition, SIRT6 deficiency increased ERS, inflammation, apoptosis and endothelial permeability, and these effects could be significantly attenuated by Ero1α knockdown. The deacetylase catalytic activity of SIRT6 was important in regulating Ero1α expression and these biological processes. Mechanistically, SIRT6 inhibited the enrichment of HIF1α and p300 at the Ero1α promoter through deacetylating H3K9, thereby antagonizing HIF1α/p300-mediated Ero1α expression. Compared with SIRT6-wild-type (SIRT6-WT) cells, cells expressing the SIRT6-H133Y-mutant and SIRT6-R65A-mutant exhibited increased Ero1α expression. Furthermore, ecSirt6-/- mice subjected to ischemia-reperfusion surgery exhibited increased Ero1α expression and ERS in CMECs and worsened injuries to microvascular barrier function and cardiac function. CONCLUSIONS: Our results revealed an epigenetic mechanism associated with SIRT6 and Ero1α expression and highlighted the therapeutic potential of targeting the SIRT6-HIF1α/p300-Ero1α axis.


Asunto(s)
Células Endoteliales , Sirtuinas , Animales , Ratones , Acetilación , Especies Reactivas de Oxígeno , Estrés Oxidativo , CME-Carbodiimida , Sirtuinas/genética
17.
Heliyon ; 9(8): e18460, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37576269

RESUMEN

A 79-year-old female patient was admitted to the hospital due to intense chest pain. Emergency percutaneous coronary intervention (PCI) revealed an occlusion in the distal portion of the left circumflex artery (LCx). The patient suffered from cardiac rupture, an uncommon yet extremely perilous condition, within 30 minutes following the procedure. This was verified through a computed tomography angiography (CTA) scan and bedside echocardiography. The etiology of cardiac rupture remains elusive, yet potential factors such as the patient's age, gender, initial acute myocardial infarction (AMI), and single-vessel disease without collateral circulation may be linked to this occurrence. This case report emphasizes that occluded tiny distal coronary arteries can also induce cardiac rupture and that a sufficient level of suspicion for the diagnosis of cardiac rupture should be raised when adequate fluid resuscitation fails to alleviate hypotension. Additionally, contrast-enhanced spiral computed tomography (CESCT) is highly effective in revealing certain pathological features associated with cardiac rupture.

18.
Eur Heart J ; 44(29): 2652-2653, 2023 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-37339164
20.
Appl Opt ; 62(9): 2292-2299, 2023 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-37132868

RESUMEN

Photothermoelectric conversion in chiral metasurfaces with thermoelectric material provides an effective way to achieve circular polarization recognition. In this paper, we propose a circular-polarization-sensitive photodetector in a mid-infrared region, which is mainly composed of an asymmetric silicon grating, a film of gold (Au), and the thermoelectric B i 2 T e 3 layer. The asymmetric silicon grating with the Au layer achieves high circular dichroism absorption due to a lack of mirror symmetry, which results in a different temperature increasing on the surface of the B i 2 T e 3 layer under right-handed circularly polarized (RCP) and left-handed circularly polarized (LCP) excitation. Then the chiral Seebeck voltage and output power density are obtained, thanks to the thermoelectric effect of B i 2 T e 3. All the works are based on the finite element method, and the simulation results are conducted by the Wave Optics module of COMSOL, which is coupled with the Heat Transfer module and Thermoelectric module of COMSOL. When the incident flux is 1.0W/c m 2, the output power density under RCP (LCP) light reaches 0.96m W/c m 2 (0.01m W/c m 2) at a resonant wavelength, which achieves a high capability of detecting circular polarization. Besides, the proposed structure shows a faster response time than that of other plasmonic photodetectors. Our design provides a novel, to the best of our knowledge, method for chiral imaging, chiral molecular detection, and so on.

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