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1.
Acta Cardiol ; 79(2): 149-158, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38628089

RESUMO

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.


Assuntos
Doença da Artéria Coronariana , Vasos Coronários , Humanos , Prognóstico , Vasos Coronários/diagnóstico por imagem , Angiografia Coronária , Estudos Retrospectivos , Microcirculação , Angina Pectoris/diagnóstico
2.
iScience ; 27(4): 109368, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38510112

RESUMO

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.

3.
Anal Bioanal Chem ; 416(7): 1561-1570, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38285227

RESUMO

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.


Assuntos
Aminobutiratos , 60658 , Herbicidas , Organofosfonatos , Humanos , Cromatografia Líquida/métodos , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico , Glicina , 60705 , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Herbicidas/análise , Cromatografia Líquida de Alta Pressão
4.
Cell Biosci ; 13(1): 197, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37915043

RESUMO

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.

5.
Signal Transduct Target Ther ; 8(1): 431, 2023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37981648

RESUMO

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.


Assuntos
Doenças Cardiovasculares , Sistema Cardiovascular , Humanos , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/terapia , Hipóxia/genética , Oxigênio , Epigênese Genética
6.
Catheter Cardiovasc Interv ; 102(7): 1210-1221, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37870101

RESUMO

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.


Assuntos
Oclusão Coronária , Intervenção Coronária Percutânea , Rajidae , Humanos , Animais , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/métodos , Estudos Retrospectivos , Resultado do Tratamento , Oclusão Coronária/terapia , Oclusão Coronária/cirurgia , Angiografia Coronária , Doença Crônica , Fatores de Risco , Sistema de Registros
7.
Artigo em Inglês | MEDLINE | ID: mdl-37674012

RESUMO

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.

8.
Clin Transl Med ; 13(8): e1377, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37598403

RESUMO

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.


Assuntos
Células Endoteliais , Sirtuínas , Animais , Camundongos , Acetilação , Espécies Reativas de Oxigênio , Estresse Oxidativo , CME-Carbodi-Imida , Sirtuínas/genética
9.
Heliyon ; 9(8): e18460, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37576269

RESUMO

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.

10.
Innovation (Camb) ; 4(5): 100489, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37636277

RESUMO

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.

11.
J Multidiscip Healthc ; 16: 2463-2470, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37649873

RESUMO

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.

12.
Sci Bull (Beijing) ; 68(17): 1954-1974, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37541793

RESUMO

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.


Assuntos
Calcificação Vascular , Doenças Vasculares , Humanos , Músculo Liso Vascular/metabolismo , Hipóxia/metabolismo , Doenças Vasculares/metabolismo , Calcificação Vascular/metabolismo , Transdução de Sinais
14.
Eur Heart J ; 44(29): 2652-2653, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37339164
15.
Appl Opt ; 62(9): 2292-2299, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-37132868

RESUMO

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.

16.
Transgenic Res ; 32(3): 153-167, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37071377

RESUMO

Muscle mass development depends on increased protein synthesis and reduced muscle protein degradation. Muscle ring-finger protein-1 (MuRF1) plays a key role in controlling muscle atrophy. Its E3 ubiquitin ligase activity recognizes and degrades skeletal muscle proteins through the ubiquitin-proteasome system. The loss of Murf1, which encodes MuRF1, in mice leads to the accumulation of skeletal muscle proteins and alleviation of muscle atrophy. However, the function of Murf1 in agricultural animals remains unclear. Herein, we bred F1 generation Murf1+/- and F2 generation Murf1-/- Duroc pigs from F0 Murf1-/- pigs to investigate the effect of Murf1 knockout on skeletal muscle development. We found that the Murf1+/- pigs retained normal levels of muscle growth and reproduction, and their percentage of lean meat increased by 6% compared to that of the wild type (WT) pigs. Furthermore, the meat color, pH, water-holding capacity, and tenderness of the Murf1+/- pigs were similar to those of the WT pigs. The drip loss rate and intramuscular fat decreased slightly in the Murf1+/- pigs. However, the cross-sectional area of the myofibers in the longissimus dorsi increased in the adult Murf1+/- pigs. The skeletal muscle proteins MYBPC3 and actin, which are targeted by MuRF1, accumulated in the Murf1+/- and Murf1-/- pigs. Our findings show that inhibiting muscle protein degradation in MuRF1-deficient Duroc pigs increases the size of their myofibers and their percentage of lean meat without influencing their growth or pork quality. Our study demonstrates that Murf1 is a target gene for promoting skeletal muscle hypertrophy in pig breeding.


Assuntos
Músculo Esquelético , Atrofia Muscular , Animais , Camundongos , Suínos , Músculo Esquelético/metabolismo , Atrofia Muscular/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Complexo de Endopeptidases do Proteassoma/farmacologia , Hipertrofia/genética , Hipertrofia/metabolismo
17.
Front Neurosci ; 17: 1146465, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37090810

RESUMO

Introduction: Working memory (WM) is a well-known fundamental ability related to various high-level cognitive functions, such as executive functioning, decision-making, and problem-solving. Although previous studies have posited that chronic exercise may improve cognitive functions, its underlying neural mechanisms and whether habitual exercise is associated with individual WM ability remain unclear. Methods: In the current study, 36 participants reported their habitual physical activity through the International Physical Activity Questionnaire (IPAQ). In addition to assessments of intelligence quotient (IQ), WM storage capacity (K score), and visuomotor coordination capacity, electroencephalogram (EEG) signals were recorded while the participants performed a WM precision task fusing conventional visual and motor retrospective cue (retro-cue) WM tasks. Results: We found that greater amounts of and higher frequencies of vigorous-intensity exercise were highly correlated with smaller recall errors in the WM precision task. Contralateral delay activity (CDA), a well-known WM-related event-related potential (ERP) component evoked by the valid retro-cue, predicted individual behavioral recall error. Participants who met the medium or high level of IPAQ criteria (the regular exercise group) showed smaller behavioral recall error and larger CDA than participants who did not meet the criteria (the irregular exercise group). The two groups did not differ in other assessments, such as IQ, WM storage capacity, and visuomotor coordination ability. Discussion: Habitual exercise was specifically correlated with individual differences in WM precision, rather than IQ, WM storage capacity, and visuomotor coordination ability, suggesting potential mechanisms of how modulations of chronic exercise improve cognition through visual and/or motor WM precision.

18.
Int J Mol Sci ; 24(6)2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36982476

RESUMO

Hypothermic oxygenated machine perfusion (HOPE) can enhance organ preservation and protect mitochondria from hypoxia-ischemic injury; however, an understanding of the underlying HOPE mechanism that protects mitochondria is somewhat lacking. We hypothesized that mitophagy may play an important role in HOPE mitochondria protection. Experimental rat liver grafts were exposed to 30 min of in situ warm ischemia. Then, grafts were procured, followed by cold storage for 3 or 4 h to mimic the conventional preservation and transportation time in donation after circulatory death (DCD) in clinical contexts. Next, the grafts underwent hypothermic machine perfusion (HMP) or HOPE for 1 h through portal vein only perfusion. The HOPE-treated group showed a better preservation capacity compared with cold storage and HMP, preventing hepatocyte damage, nuclear injury, and cell death. HOPE can increase mitophagy marker expression, promote mitophagy flux via the PINK1/Parkin pathway to maintain mitochondrial function, and reduce oxygen free radical generation, while the inhibition of autophagy by 3-methyladenine and chloroquine could reverse the protective effect. HOPE-treated DCD liver also demonstrated more changes in the expression of genes responsible for bile metabolism, mitochondrial dynamics, cell survival, and oxidative stress. Overall, HOPE attenuates hypoxia-ischemic injury in DCD liver by promoting mitophagy flux to maintain mitochondrial function and protect hepatocytes. Mitophagy could pave the way for a protective approach against hypoxia-ischemic injury in DCD liver.


Assuntos
Transplante de Fígado , Ratos , Animais , Mitofagia , Fígado/metabolismo , Hepatócitos , Perfusão , Preservação de Órgãos
19.
Neuroimage ; 269: 119902, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36708973

RESUMO

Previous work has proposed two potential benefits of retrospective attention on working memory (WM): target strengthening and non-target inhibition. It remains unknown which hypothesis contributes to the improved WM performance, yet the neural mechanisms responsible for this attentional benefit are unclear. Here, we recorded electroencephalography (EEG) signals while 33 participants performed a retrospective-cue WM task. Multivariate pattern classification analysis revealed that only representations of target features were enhanced by valid retrospective attention during retention, supporting the target strengthening hypothesis. Further univariate analysis found that mid-frontal theta inter-trial phase coherence (ITPC) and ERP components were modulated by valid retrospective attention and correlated with individual differences and moment-to-moment fluctuations on behavioral outcomes, suggesting that both trait- and state-level variability in attentional preparatory processes influence goal-directed behavior. Furthermore, task-irrelevant target spatial location could be decoded from EEG signals, indicating that enhanced spatial binding of target representation is vital to high WM precision. Importantly, frontoparietal theta-alpha phase-amplitude coupling was increased by valid retrospective attention and predicted the reduced random guessing rates. This long-range connection supported top-down information flow in the engagement of frontoparietal networks, which might organize attentional states to integrate target features. Altogether, these results provide neurophysiological bases that retrospective attention improves WM precision by enhancing flexible target representation and emphasize the critical role of the frontoparietal attentional network in the control of WM representations.


Assuntos
Atenção , Memória de Curto Prazo , Humanos , Memória de Curto Prazo/fisiologia , Estudos Retrospectivos , Atenção/fisiologia , Eletroencefalografia , Cognição
20.
Hum Brain Mapp ; 44(3): 937-947, 2023 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-36250701

RESUMO

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in school-age children. Attentional orientation is a potential clinical diagnostic marker to aid in the early diagnosis of ADHD. However, the underlying pathophysiological substrates of impaired attentional orienting in childhood ADHD remain unclear. Electroencephalography (EEG) was measured in 135 school-age children (70 with childhood ADHD and 65 matched typically developing children) to directly investigate target localization during spatial selective attention through univariate ERP analysis and information-based multivariate pattern machine learning analysis. Compared with children with typical development, a smaller N2pc was found in the ADHD group through univariate ERP analysis. Children with ADHD showed a lower parieto-occipital multivariate decoding accuracy approximately 240-340 ms after visual search onset, which predicts a slower reaction time and larger standard deviation of reaction time. Furthermore, a significant correlation was found between N2pc and decoding accuracy in typically developing children but not in children with ADHD. These observations reveal that impaired attentional orienting in ADHD may be due to inefficient neural encoding responses. By using a personalized information-based multivariate machine learning approach, we have advanced the understanding of cognitive deficits in neurodevelopmental disorders. Our study provides potential research directions for the early diagnosis and optimization of personalized intervention in children with ADHD.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Humanos , Criança , Eletroencefalografia , Tempo de Reação/fisiologia
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