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1.
Front Mol Biosci ; 9: 851966, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35923469

RESUMO

Background: Autophagy is a highly regulated and evolutionarily conserved process in eukaryotes which is responsible for protein and organelle degradation. Although this process was described over 60 years ago, the selective autophagy of mitochondria (mitophagy) was recently coined in 2005. Research on the topic of mitophagy has made rapid progress in the past decade, which proposed to play critical roles in human health and disease. This study aimed to visualize the scientific outputs and research trends of mitophagy. Methods: Articles and reviews related to the topic of mitophagy were retrieved from the Web of Science Core Collection on 30 November 2021. Two kinds of software (CiteSpace and VOSviewer) were used to perform a visualized analysis of countries/regions, institutions, authors, journals, references, and keywords. Results: From 2005 to 2021, total 5844 publications on mitophagy were identified for final analysis. The annual number of publications grew yearly over the past 17 years. United States (N = 2025) and Chinese Academy of Sciences is the leading country and institute (N = 112) ranked by the number of publications, respectively. The most productive author was Jun Ren (N = 38) and Derek P. Narendra obtained the most co-cited times (2693 times). The journals with the highest output and the highest co-citation frequency were Autophagy (N = 208) and Journal of Biological Chemistry (co-citation: 17226), respectively. Analyses of references and keywords suggested that "mechanism of mitochondrial quality control", "molecule and signaling pathway in mitophagy", and "mitophagy related diseases" were research hotspots, and parkin-mediated mitophagy and its roles in skeletal muscle and inflammation-related diseases may be the frontiers of future research. Conclusion: Although mitophagy research has flourished and attracted attention from all over the world, the regional imbalance in the development of mitophagy research was observed. Our results provided a comprehensive global research landscape of mitophagy from 2005- 2021 from a perspective of bibliometrics, which may serve as a reference for future mitophagy studies.

2.
Front Endocrinol (Lausanne) ; 13: 895360, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35813614

RESUMO

Background: Diabetic nephropathy (DN) is a serious complication among patients with diabetes. Elucidating its pathogenesis is crucial for identifying novel biomarkers and therapeutic targets for DN. Methods: DN tissues were harvested for examining MALAT1, LIN28A and Nox4. Human kidney-2 (HK-2) cells were treated with high glucose (HG) for establishing a cell model of DN. Cell viability was examined by MTT assay. HG-induced cell apoptosis and secretion of TNF-α and IL-6 were analyzed by TUNEL and ELISA assays, respectively. RIP and RNA pull-down assays were applied to analyze the interaction between MALAT1, LIN28A and Nox4 in HK-2 and human embryonic kidney 293T (HEK-293T) cells. A rat model of DN was established to determine the role of MALAT1 in DN in vivo. Results: MALAT1, LIN28A and Nox4 were upregulated in DN tissues and HG-treated HK-2 cells. Overexpression of MALAT1, LIN28A or Nox4 reduced cell viability and enhanced cell apoptosis, ROS generation and secretion of inflammatory cytokines in HG-treated HK-2 cells, whereas knockdown of MALAT1, LIN28A or Nox4 exerted opposite effects. Furthermore, MALAT1 directly interacted with LIN28A. Moreover, MALAT1 facilitated the interaction between LIN28A and Nox4 to increase Nox4 stability. Knockdown of Nox4 relieved HG-induced injury by suppressing the AMPK/mTOR signaling in HK-2 cells. Knockdown of MALAT1 alleviated renal tubular epithelial injury by suppressing LIN28A and the Nox4/AMPK/TOR signaling in DN. Conclusion: MALAT1 activates the AMPK/mTOR signaling via interacting with LIN28A to stabilize Nox4 mRNA, thereby aggravating high glucose-induced renal tubular epithelial injury. Our findings provide potential therapeutic targets for DN.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , RNA Longo não Codificante/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Animais , Linhagem Celular , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Glucose , Humanos , Rim , NADPH Oxidase 4/genética , RNA Longo não Codificante/genética , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Ratos , Serina-Treonina Quinases TOR/genética
3.
Eur Radiol ; 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35727319

RESUMO

OBJECTIVES: The presence of non-alcoholic fatty liver disease (NAFLD) has been associated with major adverse cardiovascular events (MACEs); however, the mechanisms that initiate the risk for MACEs in patients with NAFLD remain unknown. We sought to investigate whether plaque progression (PP), determined by coronary CT angiography (CCTA), moderate the relationship between NAFLD and MACEs. METHODS: A total of 1683 asymptomatic participants (mean age, 63.3 ± 9.4 [range, 38-85] years; 1117 men) who underwent baseline and follow-up CCTA examination were prospectively included in our study. All of the participants were divided into the NAFLD and non-NAFLD groups. PP was determined by follow-up CCTA. The primary endpoint was MACEs, defined as the composite of all-cause death, nonfatal myocardial infarction, and unplanned hospitalization for acute coronary syndrome leading to revascularization. RESULTS: At follow-up CCTA, participants with NAFLD showed higher incidence of PP than those without [33.0% (248/752) vs. 16.6% (155/931), p < 0.001]. Compared with non-NAFLD participants, participants with NAFLD had a lower 9.7-year event-free survival rate (80.9 vs. 66.4%, log-rank p < 0.001). Cox regression analysis revealed NAFLD was significantly associated with MACEs (HR = 1.63, 95% CI: 1.28 to 2.06, p < 0.001) after adjusting for covariables. However, this association was no longer significant after adjustment for PP (HR = 1.10, 95% CI: 0.84 to 1.45, p = 0.496). The mediation analysis revealed that PP had a significant indirect effect (ß = 0.0587, 95% CI: 0.0424 to 0.08, p < 0.001) and mediated 99.8% (p = 0.002) for the relationship between NAFLD and MACEs. CONCLUSIONS: Plaque progression, identified by follow-up CCTA, mediates the relationship between NAFLD and MACEs. KEY POINTS: The incidence of CCTA-identified PP was higher for participants with NAFLD than those without NAFLD (248/752 [33.0%] vs. 155/931 [16.6%], p < 0.001). Participants with NAFLD had a lower 9.7-year event-free survival rate than those without NAFLD (66.4% vs. 80.9%, log-rank p < 0.001). The mediation analysis revealed that PP had a significant indirect effect (ß = 0.0587, 95% CI: 0.0424 to 0.08, p < 0.001) and mediated 99.8% (p = 0.002) for the relationship between NAFLD and MACEs.

4.
Ann Transl Med ; 10(10): 614, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35722356

RESUMO

Background: Polymyxins antibiotics have become the first-line clinical drugs in the treatment of refractory gram-negative bacterial infections. Currently, there is a lack of clinical studies on the effect of extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy (CRRT) on polymyxin concentrations. The purpose of this report was to investigate the changes in the plasma concentrations of Colistin sulfate during ECMO and CRRT and to provide drug administration programs for critically ill patients receiving ECMO and CRRT. Case Description: In this case report, a patient with septic shock caused by severe acute pancreatitis, with abdominal pain and dyspnea as the main manifestations, was treated with ECMO combined with CRRT for life support and multiple anti-infective drugs. However, the symptoms of infection had not got improved, the inflammatory indicators remain high and the body temperature fluctuates repeatedly 36.7-38.5 ℃, was considered as carbapenem-resistant organisms (CROs) infection, and was empirically given Colistin sulfate for anti-infection treatment. Finally, the patient's condition improved and ECMO and CRRT were gradually withdrawn. At the same time, the plasma concentrations of Colistin sulfate before and after ECMO combined with CRRT, was monitored to determine the changes in the plasma concentrations of Colistin sulfate during ECMO and CRRT. Trough and peak concentrations on the 4th day of venovenous ECMO (VV-ECMO) combined with CRRT were 0.36 and 0.98 mg/L, respectively. After withdrawal of ECMO and CRRT, the concentrations were, respectively, 0.27 and 0.34 mg/L for trough concentrations, and 0.82 and 0.98 mg/L for peak concentrations. The data showed that there were no significant differences in the trough and peak concentrations of Colistin sulfate before and after ECMO and CRRT. No adverse effects occurred during follow-up. Conclusions: There were no significant differences in the trough and peak concentrations of Colistin sulfate before and after ECMO and CRRT. Therefore, no dose modification is required for Colistin sulfate in patients receiving ECMO with CRRT.

5.
Eur Radiol ; 2022 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-35567603

RESUMO

OBJECTIVES: Immune checkpoint inhibitor (ICI)-associated myocarditis is a potentially fatal complication. Sparse published researches evaluated the prognostic value of cardiovascular magnetic resonance feature tracking (CMR-FT) for ICI-associated myocarditis. METHODS: In the single-center retrospective study, 52 patients with ICI-associated myocarditis and CMR were included from August 2018 to July 2021. The ICI-associated myocarditis was diagnosed by using the clinical criteria of the European Society of Cardiology guidelines. Major adverse cardiovascular events (MACE) were comprised of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. RESULTS: During a median follow-up of 171 days, 14 (27%) patients developed MACE. For patients with MACE, the global circumferential strain (GCS), global radial strain (GRS), global longitudinal strain (GLS), and left ventricular ejection fraction (LVEF) were significantly worse and native T1 values and late gadolinium enhancement (LGE) extent were significantly increased, compared with patients without MACE (p < 0.05). The GLS remained the independent factor associated with a higher risk of MACE (hazard ratio (HR): 2.115; 95% confidence interval (CI): 1.379-3.246; p = 0.001) when adjusting for LVEF, LGE extent, age, sex, body mass index, steroid treatment, and prior cardiotoxic chemotherapy or radiation. After adjustment for LVEF, the GLS remained the independent risk factor associated with a higher rate of MACE among patients with a preserved LVEF (HR: 1.358; 95% CI: 1.007-1.830; p = 0.045). CONCLUSIONS: GLS could provide independent prognostic value over GCS, GRS, traditional CMR features, and clinical features in patients with ICI-associated myocarditis. KEY POINTS: • The global circumferential strain (GCS), global radial strain (GRS), and global longitudinal strain (GLS) by cardiovascular magnetic resonance feature tracking were significantly impaired in patients with an immune checkpoint inhibitor (ICI)-associated myocarditis. • GLS was still significantly impaired in patients with preserved left ventricular ejection fraction. • The worse GLS was an independent risk factor over GCS, GRS, traditional CMR features, and clinical features for predicting major adverse cardiovascular events in patients with ICI-associated myocarditis.

6.
Acad Radiol ; 2022 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-35469720

RESUMO

RATIONALE AND OBJECTIVES: The value of myocardial strain for reflecting fibrosis in patients with hypertrophic cardiomyopathy (HCM) on cardiac magnetic resonance (CMR) has not been definite. We aim to explore whether there are underlying non-contrast parameters to evaluate myocardial fibrosis and screen which may be the best. MATERIALS AND METHODS: We retrospectively included 127 HCM patients (89 men; average age 46.6 ± 15.6 years) and 30 healthy controls (20 men; average age 52.0 ± 13.2 years) who have undergone late gadolinium enhancement (LGE) CMR. Next, 127 HCM patients were divided randomly into two sets including training cohort and validation cohort. Strain and imaging parameters were measured and analyzed statistically. RESULTS: Based on univariate and multivariate analysis, segmental circumferential strain (SCS) (p < 0.001) and maximal wall thickness (MWT) (p < 0.001) may differentiate myocardial segments with or without LGE as significant biomarkers for both sets. The area under the curve (AUC) was 0.803 (95% CI 0.785-0.820) for SCS and 0.777 (95% CI 0.759-0.795) for MWT to identify myocardial fibrosis. When combining SCS >-13.9% and MWT >16.4mm, the specificity of the model (AUC = 0.779; 95% CI 0.760-0.796) achieved the highest 93.9%, with a sensitivity of 61.8%. CONCLUSION: Strain analysis in HCM holds promise for myocardial fibrosis detection and SCS is the best strain parameter based on CMR. Nevertheless, the model of combining SCS and MWT could achieve the highest specificity for fibrotic diagnosis.

7.
Animals (Basel) ; 12(8)2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35454282

RESUMO

Twenty-four healthy castrated male Holstein growing cattle, with similar body weight (301 ± 11.5 kg), were enrolled in this study and randomly allocated into two groups (12/pen). Holstein growing cattle in the LPT (low NFC/NDF pelleted TMR) group were fed basal pelleted TMR with a low NFC/NDF ratio (NFC/NDF = 1.07), while the HPT (high NFC/NDF pelleted TMR) group were fed with a high NFC/NDF ratio diet (NFC/NDF = 1.71). The results showed that: (1) Body measurements were found to be increased for the LPT group (p < 0.05); compared with the HPT group, feed intake to gain ratio and feed cost in the LPT group were decreased by 12.24% and 15.35%, respectively (p < 0.01). Compared with the HPT group, the LPT group tended to increase chest girth. (2) Digestibility of DM and NDF in the LPT group was higher (p < 0.05) than in the HPT group, being increased by 3.41% and 4.26%, respectively, and increased digestibility of ADF in the LPT group was significant (p < 0.01). (3) The daily feed consumption of NDF in the LPT group was higher than that in the HPT group and the daily rumination time and chewing time in the LPT group were longer than that in the HPT group (p < 0.05). (4) Compared with the LPT group, the parameter of pH, microbial protein and acetate: propionate (p < 0.05) in the HPT group were decreased by 8.57%, 12.46% and 23.71%, respectively. In contrast, the concentration of total volatile fatty acids, acetate and propionate were higher (p < 0.05) in the HPT group, and increased by 13.49%, 19.59% and 52.70%, respectively. (5) Compared with the LPT group, rumen fluid in the HPT group diet up-regulated the mRNA expression levels of BRECs pro-inflammatory factor IL-1ß and TNF-α (p < 0.05), and meanwhile, up-regulated the mRNA expression levels of BRECs pro-inflammatory factor IL-6 (p < 0.01); compared with the LPT group, rumen fluid in the HPT group diet up-regulated the mRNA expression levels of CCL28 and CCL20 (p < 0.05) chemokines in CCL types of BRECs; in addition, compared with the LPT group, rumen fluid in the HPT group up-regulated the mRNA expression levels of CXCL2, CXCL3, CXCL9 and CXCL14 chemokines in CXCL types of BRECs (p < 0.01), and the mRNA expression levels of the CXCL5 chemokine tended to be increased (p = 0.06).

8.
AJR Am J Roentgenol ; 219(2): 199-211, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35293232

RESUMO

BACKGROUND. Coronary MRA is commonly performed at 1.5 T using SSFP acquisitions. Coronary MRA performed at 3 T using SSFP is limited due to impaired fat suppression and has been typically investigated using contrast-enhanced techniques. A Dixon fat-water separation gradient-recalled echo (GRE) method may enable high-quality unenhanced 3-T coronary MRA. OBJECTIVE. The purpose of this study was to compare 1.5-T SSFP and 3-T Dixon water-fat separation GRE methods for unenhanced whole-heart coronary MRA in patients with suspected coronary artery disease (CAD). METHODS. This prospective study included 44 patients (27 men and 17 women; mean age, 59 ± 8 [SD] years) with an intermediate to high risk of CAD who underwent both 1.5-T SSFP and 3-T Dixon GRE coronary MRA examinations before undergoing coronary angiography (CAG). Two radiologists independently assessed coronary arteries in terms of subjective image quality (on a scale of 1-5, with 5 denoting the highest image quality), number of visible segments, apparent contrast-to-noise ratio (CNR; vs myocardium), and presence of significant stenoses. Methods were compared using the mean of the readers' values for apparent CNR and using consensus interpretations for other measures. CAG served as the reference standard for detecting the presence of stenoses. RESULTS. Expressed as a kappa coefficient, interobserver agreement was 0.85 for image quality, 0.85 for segment visibility, and 0.83 for stenosis, and expressed as an intraclass correlation coefficient, interobserver agreement was 0.92 for apparent CNR. The mean overall image quality score was 4.0 ± 1.1 for 3-T Dixon GRE versus 3.0 ± 1.2 for 1.5-T SSFP. The percentage of visible segments for 3-T Dixon GRE versus 1.5-T SSFP was 96.7% versus 88.9% for all segments, 96.9% versus 90.1% for distal segments, and 93.1% versus 77.2% for branch segments. The mean overall apparent CNR was 93.2 ± 29.2 for 3-T Dixon GRE versus 80.8 ± 27.9 for 1.5-T SSFP. The 3-T Dixon GRE method, compared with the 1.5-T SSFP method, showed higher sensitivity and specificity in per-vessel analysis (87.9% vs 77.3% and 83.3% vs 60.6%, respectively), per-segment analysis (84.6% vs 74.8% and 90.9% vs 79.6%, respectively), and per-segment analysis of distal and branch segments (89.7% vs 75.9% and 89.7% vs 73.7%, respectively). CONCLUSION. For unenhanced coronary MRA, 3-T unenhanced Dixon GRE had better image quality and diagnostic performance than 1.5-T SSFP, particularly for distal and branch segments. CLINICAL IMPACT. The 3-T Dixon GRE technique may be preferred to the current clinical standard of the 1.5-T SSFP technique for unenhanced coronary MRA.


Assuntos
Meios de Contraste , Angiografia por Ressonância Magnética , Idoso , Constrição Patológica , Angiografia Coronária , Feminino , Humanos , Angiografia por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Água
10.
J Am Coll Cardiol ; 79(1): 35-48, 2022 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-34991787

RESUMO

BACKGROUND: Reperfusion therapy for acute myocardial infarction (MI) is lifesaving. However, the benefit of reperfusion therapy can be paradoxically diminished by reperfusion injury, which can increase MI size. OBJECTIVES: Hemorrhage is known to occur in reperfused MIs, but whether hemorrhage plays a role in reperfusion-mediated MI expansion is not known. METHODS: We studied cardiac troponin kinetics (cTn) of ST-segment elevation MI patients (n = 70) classified by cardiovascular magnetic resonance to be hemorrhagic (70%) or nonhemorrhagic following primary percutaneous coronary intervention. To isolate the effects of hemorrhage from ischemic burden, we performed controlled canine studies (n = 25), and serially followed both cTn and MI size with time-lapse imaging. RESULTS: CTn was not different before reperfusion; however, an increase in cTn following primary percutaneous coronary intervention peaked earlier (12 hours vs 24 hours; P < 0.05) and was significantly higher in patients with hemorrhage (P < 0.01). In hemorrhagic animals, reperfusion led to rapid expansion of myocardial necrosis culminating in epicardial involvement, which was not present in nonhemorrhagic cases (P < 0.001). MI size and salvage were not different at 1 hour postreperfusion in animals with and without hemorrhage (P = 0.65). However, within 72 hours of reperfusion, a 4-fold greater loss in salvageable myocardium was evident in hemorrhagic MIs (P < 0.001). This paralleled observations in patients with larger MIs occurring in hemorrhagic cases (P < 0.01). CONCLUSIONS: Myocardial hemorrhage is a determinant of MI size. It drives MI expansion after reperfusion and compromises myocardial salvage. This introduces a clinical role of hemorrhage in acute care management, risk assessment, and future therapeutics.


Assuntos
Hemorragia/diagnóstico por imagem , Traumatismo por Reperfusão Miocárdica/diagnóstico por imagem , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem , Animais , Modelos Animais de Doenças , Cães , Humanos , Imagem Cinética por Ressonância Magnética , Miocárdio/patologia , Necrose , Intervenção Coronária Percutânea , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Terapia de Salvação , Tempo para o Tratamento , Troponina/sangue
11.
Sci Rep ; 12(1): 913, 2022 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042878

RESUMO

Reassessing the continuing need for and choice of antibiotics by using an antibiotic "time out'' program may reduce unnecessary treatment. This study aimed to explore the effect of an antibiotic stewardship program (ASP) on the antibiotics consumption, incidence of resistant bacterial infections and overall hospital mortality in a tertiary medical center during the study period 2012-2014. An ASP composed of multidisciplinary strategies including pre-prescription approval and post-approval feedback and audit, and a major "time out'' intervention (shorten the default antibiotic prescription duration) usage was introduced in year 2013. Consumption of antibiotics was quantified by calculating defined daily doses (DDDs). Interrupted time series (ITS) analysis was used to explore the changes of antibiotics consumption before and after intervention, accounting for temporal trends that may be unrelated to intervention. Our results showed that following the intervention, DDDs showed a decreased trend in overall (in particular the major consumed penicillins and cephalosporins), in both intensive care unit (ICU) and non-ICU, and in non-restrictive versus restrictive antibiotics. Importantly, ITS analysis showed a significantly slope change since intervention (slope change p value 0.007), whereas the incidence of carbapenem-resistant and vancomycin-resistant pathogens did not change significantly. Moreover, annual overall mortality rates were 3.0%, 3.1% and 3.1% from 2012 to 2014, respectively. This study indicates that implementing a multi-disciplinary strategy to shorten the default duration of antibiotic prescription can be an effective manner to reduce antibiotic consumption while not compromising resistant infection incidence or mortality rates.


Assuntos
Gestão de Antimicrobianos
12.
Br J Radiol ; 95(1133): 20201060, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35084208

RESUMO

OBJECTIVES: To evaluate the performance of a deep learning-based method to automatically quantify left ventricular (LV) function from MR images in different cardiomyopathy. METHODS: This retrospective study included MRI data sets from 2013 to 2020. Data on left ventricular function from patients with hypertrophic cardiomyopathy (HCM), patients with dilated cardiomyopathy (DCM), and healthy participants were analyzed. MRI data from a total of 388 patients were measured manually and automatically.The performance of Convolutional Neural Networks (CNNs) was evaluated based on the manual notes of two experienced observers: (a) LV segmentation accuracy, and (b) LV functional parameter accuracy. Bland-Altman analysis, Receiver operating Characteristic (ROC) curve analysis and Pearson correlation analysis were used to evaluate the consistency between fully automatic and manual diagnosis of HCM and DCM. RESULTS: The deep-learning CNN performed best in HCM in evaluating LV function and worst in DCM. Compared with manual analysis, four parameters of LV function in the HCM group showed high correlation (r at least >0.901), and the correlation of DCM in all parameters was weaker than that of HCM, especially EF (r2 = 0.776) and SV (r2 = 0.645). ROC curve analysis indicated that at the optimal cut-off value, EF from automatic segmentation identified DCM and HCM patients with sensitivity of 92.31 and 78.05%, specificity of 82.96 and 54.07%, respectively. CONCLUSION: Among different heart diseases, the analysis of cardiac function based on deep-learning CNN may have different performances, with DCM performing the worst and HCM the best and thus, special attention should be paid to DCM patients when assessing LV function through artificial intelligence method. LV function parameter obtained by artificial intelligence method may play an important role in the future AI diagnosis of HCM and DCM. ADVANCES IN KNOWLEDGE: These data for the first time objectively evaluate the performance of a commercially available deep learning-based method in cardiac function evaluation of different cardiomyopathy and point out its advantages and disadvantages in different cardiomyopathy. This work did not attempt to design the algorithm itself, but rather applied an already existing method to a test dataset of clinical data and evaluated the results for a limited number of cardiomyopathy.


Assuntos
Cardiomiopatias , Cardiomiopatia Dilatada , Cardiomiopatia Hipertrófica , Inteligência Artificial , Cardiomiopatia Dilatada/diagnóstico por imagem , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Função Ventricular Esquerda
13.
J Magn Reson Imaging ; 55(2): 579-591, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34254384

RESUMO

BACKGROUND: 3.0 T non-contrast-enhanced nitroglycerin (NTG)-assisted whole-heart coronary magnetic resonance angiography (MRA) employing Dixon water-fat separation and compressed SENSE (CS-SENSE) acceleration is a promising method for diagnosing coronary artery disease (CAD). PURPOSE: To evaluate the diagnostic performance of this technique for detecting clinically-relevant (≥50% diameter reducing) CAD and to evaluate the difference in NTG-induced coronary vasodilation between patients with and without clinically-relevant CAD. STUDY TYPE: Prospective. POPULATION: Sixty-six patients with suspected CAD. FIELD STRENGTH/SEQUENCE: 3.0 T; CSSENSE, Dixon water-fat separation, three-dimensional segmented turbo field gradient-echo sequence for whole-heart coronary MRA. ASSESSMENT: Overall image quality of coronary MRA was calculated on the basis of all visible coronary segments. The diagnostic performance of coronary MRA for detecting a ≥50% reduction in coronary artery diameter with and without NTG was compared using X-ray coronary angiography (CAG) as the reference. According to CAG, patients were divided into a non-clinically-relevant CAD group and clinically-relevant CAD group, and the difference in NTG-induced vasodilation between the groups was evaluated. STATISTICAL TESTS: Unpaired/paired Student's t-test, Mann-Whitney U test, paired Wilcoxon signed-rank test, χ2 test, McNemar test. A two-tailed P value <0.05 was considered significant. RESULTS: Overall image quality was increased significantly in the coronary MRA images after NTG. The diagnostic performance of the non-NTG vs. NTG-assisted coronary MRA was as follows on a per-patient basis: sensitivity 94.3% vs. 94.3%, specificity 64.5% vs. 83.9%, positive predictive value 75.0% vs. 86.8%, negative predictive value 90.9% vs. 92.9%, and accuracy 80.3% vs. 89.4%, respectively. NTG-induced vasodilation was significantly lower in the clinically-relevant CAD group than in the non-clinically-relevant CAD group (13.7 ± 8.1% vs. 24.1 ± 16.3%). DATA CONCLUSION: Non-contrast Dixon water-fat separation CS-SENSE coronary MRA at 3.0 T can noninvasively detect clinically-relevant CAD and sublingual NTG improved performance. Combining pre- and post-NTG coronary MRA may provide a simple noninvasive and nonionizing test to evaluate coronary vasodilation function. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.


Assuntos
Nitroglicerina , Água , Angiografia Coronária , Vasos Coronários/diagnóstico por imagem , Humanos , Angiografia por Ressonância Magnética , Estudos Prospectivos , Sensibilidade e Especificidade , Vasodilatadores
14.
Acad Radiol ; 29 Suppl 4: S82-S90, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34127363

RESUMO

RATIONALE AND OBJECTIVES: The clinical utility of Dixon water-fat separation coronary MR angiography (CMRA) with compressed sensing (CS) reconstruction has not been determined in a patient population. This study was designed to evaluate the performance of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA sequence in vitro and in vivo. MATERIALS AND METHODS: In vitro phantom MRI, we compared key parameters of the SENSE and CS images. And in this prospective in vivo study, from November 2019 to October 2020, 94 participants were recruited for 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA. The accuracy of CMRA for detecting a ≥ 50% reduction in diameter was determined using X-ray coronary angiography (CA) as the reference method. RESULTS: Compared with SENSE, CS with an appropriate acceleration factor offers both higher SNR/CNR (p < 0.05) and a shortened acquisition. Fifty-eight patients successfully completed the CMRA and CA. The sensitivity, specificity, positive predictive values, negative predictive values, and accuracy of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA according to a patient-based analysis were 96.4%, 66.7%, 73.0%, 95.2% and 81.0%, respectively. The area under the receiver-operator characteristic (ROC) curve (AUC) of 3.0 T non-contrast-enhanced Dixon water-fat separation CS whole-heart CMRA for detecting significant coronary artery stenosis is 0.908, 0.895, and 0.904 in patient-, vessel-, and segment-based analyses respectively. CONCLUSION: 3.0 T non-contrast-enhanced Dixon water-fat separation whole-heart CMRA using appropriate CS is a promising noninvasive and radiation-free technique to detect clinically significant coronary stenosis on patients with suspected CAD.


Assuntos
Estenose Coronária , Angiografia por Ressonância Magnética , Meios de Contraste , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Humanos , Angiografia por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética , Estudos Prospectivos , Água
15.
Metabolism ; 128: 154959, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34953916

RESUMO

BACKGROUND: Mitochondrial biogenesis and dysfunction are associated with renal tubular epithelial cell injury and the pathophysiological development of diabetic nephropathy (DN). Adiponectin (APN) is a plasma hormone protein specifically secreted by adipocytes. In the present study, we studied the effects of APN on mitochondrial biogenesis and function in renal tubular epithelial cells and examined the mechanisms underlying its actions. MATERIALS: A rat model of type 2 diabetes mellitus (T2DM) was established using streptozotocin (STZ), and an NRK-52E culture model exposed to high glucose was also used. We found that APN treatment alleviated kidney histopathological injury in T2DM rats, reduced fasting blood glucose (FBG) and postprandial blood glucose (PBG) levels, maintained stable animal weight, promoted cell viability, inhibited apoptosis and the formation of autophagosomes, and also increased mitochondrial mass, mitochondrial DNA (mtDNA) content and mitochondrial membrane potential (MMP) in vivo and in vitro. RESULTS: We found that the expression of AdipoR1/CREB/PGC-1α/TFAM pathway proteins and respiratory chain complex subunits CO1, CO2, CO3, ATP6 and ATP8 were significantly increased after APN treatment. We also found that inhibition of cAMP response element binding protein (CREB) weakened the effects of APN in NRK-52E cells treated with high glucose. Coimmunoprecipitation experiments showed that AdipoR1 interacted with CREB. CONCLUSION: APN promoted mitochondrial biogenesis and function in renal tubular epithelial cells by regulating the AdipoR1/CREB/PGC-1α/TFAM pathway. APN has the potential to serve as an effective drug for the treatment of DN.


Assuntos
Adiponectina/farmacologia , Nefropatias Diabéticas/tratamento farmacológico , Túbulos Renais/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Animais , Células Cultivadas , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Células Epiteliais/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiologia , Masculino , Mitocôndrias/fisiologia , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Estreptozocina , Fatores de Transcrição/fisiologia
16.
Food Chem ; 366: 130613, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34304136

RESUMO

A colorimetric and fluorescence dual-signal method based on sulfur quantum dots (SQDs) was established for determination of iron (II) (Fe2+) and H2O2 in foods. Due to the complexation of Fe2+ with SQD, Fe2+ can cause fluorescence quenching of SQDs, and the color of the mixed solution changed from light yellow to deep green. By use of Fenton reaction, H2O2 can restore the quenched fluorescence of SQDs, and the color of the mixture changed from green to colorless. The concentration of Fe2+ and H2O2 has a good linear relationship with the fluorescence intensity and absorbance in the range of 2.5-55 µM and 1.25-500 µM, and the detection limits were 1.41 µM and 0.54 µM, respectively. For determination of H2O2, the linear ranges were 1.17-1.97 mM and 0.867-1.50 mM, and the detection limits were 0.03 µM and 0.06 µM, respectively.


Assuntos
Pontos Quânticos , Colorimetria , Peróxido de Hidrogênio , Ferro , Enxofre
17.
Animals (Basel) ; 11(11)2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34827778

RESUMO

Sixty castrated male Haimen white growing goats with an initial age of 100 days old and similar body weight (16 ± 1.5 kg) were selected and randomly allocated into five groups with three replicates in each group with four goats in each pen (5 m × 3.2 m). Goats in the control group (CG) were fed a basal pelleted total mixed ration supplemented with 30% alfalfa hay pellet, while experimental treatments (G6, G12, G18, or G24) were supplemented with four levels (6%, 12%, 18%, or 24%) of GBLR replacing alfalfa hay pellet in the diet, separately. Results showed that (1) the final body weight, average daily gain, and average feed intake of G18 was significantly higher (p < 0.05) than CG; in contrast, the feed conversion ratio of G18 was significantly lower than CG and G12 (p < 0.05); the feed cost per head per day of CG was significantly higher (p < 0.05) than that of G18 and G24, and exhibited obvious linearly decrease (p = 0.04) with increasing GBLR supplementation; and apparent total-tract digestibility of DM and NDF in GBLR treatments were significantly higher (p < 0.05) than CG; (2) alanine transaminase (ALT) concentration in the G18 group was significantly lower (p < 0.05) than those in the control group; aspartate transaminase (AST) concentration in the G24 was significantly lower (p < 0.05) than those in the control group, and an increase in dietary level of GBLR tended to result in a linear decrease (p = 0.09) in the concentration of serum AST; (3) the concentration of malondialdehyde (MDA) demonstrated a tendency to decrease (p = 0.06) linearly with increasing GBLR supplementation; however, glutathione peroxidase (GSH-PX) activity in G12 was significantly higher (p < 0.05) than CG, G6, and G24; in addition, superoxide dismutase (SOD) activity in G18 was significantly higher (p < 0.05) than CG and G6; concentration of immunoglobulin M (IgM), immunoglobulin G (IgG), and immunoglobulin A (IgA) were not affected by GBLR, but increasing dietary GBLR showed a tendency (p = 0.08) to linearly increase the IgG concentration; the content of interleukin 4 (IL4) was significantly higher (p < 0.05) in G12, G18, and G24 than that in CG and G6; (4) There were similar NH3-N, pH, TVFA, and butyrate for goats fed different levels of GBLR supplementation; the C2 (p = 0.07) and acetate: propionate (p = 0.06) demonstrated a tendency to increase linearly with increasing level of GBLR supplementation, separately; however, it was observed that concentration of propionate showed a tendency to decrease (p = 0.08) linearly in response to GBLR supplementation; and (5) Increasing dietary GBLR tended to linearly enhance the lightness (L*) (p = 0.07) and yellowness (b*) (p = 0.09) values of longissimus dorsi muscles; the redness (a*) value in G18 was significantly higher than that in CG (p < 0.05).

18.
Mol Med ; 27(1): 137, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34711178

RESUMO

BACKGROUND: Obesity-related nephropathy (ORN) has become one of the leading causes of end-stage renal disease and has tripled over the past decade. Previous studies have demonstrated that decreased reactive oxygen species production may contribute to improving ORN by ameliorating oxidative stress injury. Here, IκB kinase (IKK) was hypothesized to inactivate the deubiquitination activity of cylindromatosis (CYLD) by activating the phosphorylation of CYLD, thus promoting the ubiquitination of NF-E2-related factor 2 (Nrf2) and further aggravating oxidative stress injury of the kidney in ORN. This study was aimed to confirm this hypothesis. METHODS: Haematoxylin and eosin (HE), periodic acid-Schiff (PAS) and Oil Red O staining were performed to assess histopathology. Dihydroethidium (DHE) staining and MDA, SOD, CAT, and GSH-PX assessments were performed to measure reactive oxygen species (ROS) production. Immunohistochemical (IHC) staining, qRT-PCR and/or western blotting were performed to assess the expression of related genes. JC-1 assays were used to measure the mitochondrial membrane potential (ΔΨm) of treated HK-2 cells. Co-immunoprecipitation experiments (Co-IP) were used to analyse the interaction between CYLD and Nrf2 in ORN. RESULTS: ORN in vivo and in vitro models were successfully constructed, and oxidative stress injury was detected in the model tissues and cells. Compared with the control groups, the phosphorylation level of CYLD increased while Nrf2 levels decreased in ORN model cells. An IKK inhibitor reduced lipid deposition, ROS production, CYLD phosphorylation levels and ΔΨm in vitro, which were reversed by knockdown of CYLD. Nrf2 directly bound to CYLD and was ubiquitinated in ORN cells. The proteasome inhibitor MG132 activated the Nrf2/ARE signalling pathway, thereby reversing the promoting effect of CYLD knockdown on oxidative stress. CONCLUSION: IKK inactivates the deubiquitination activity of CYLD by activating the phosphorylation of CYLD, thus promoting the ubiquitination of Nrf2 and further aggravating oxidative stress injury of the kidney in ORN. This observation provided a feasible basis for the treatment of kidney damage caused by ORN.


Assuntos
Enzima Desubiquitinante CYLD/metabolismo , Quinase I-kappa B/metabolismo , Nefropatias/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Obesidade/metabolismo , Amidas/farmacologia , Animais , Linhagem Celular , Enzima Desubiquitinante CYLD/genética , Humanos , Quinase I-kappa B/antagonistas & inibidores , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/etiologia , Nefropatias/patologia , Metabolismo dos Lipídeos , Lipoproteínas LDL/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/antagonistas & inibidores , Obesidade/complicações , Obesidade/patologia , Estresse Oxidativo , Oxirredutases/metabolismo , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Tiofenos/farmacologia , Ubiquitinação
19.
J Cardiovasc Magn Reson ; 23(1): 104, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34587984

RESUMO

BACKGROUND: T2* cardiovascular magnetic resonance (CMR) is commonly used in the diagnosis of intramyocardial hemorrhage (IMH). For quantifying IMH with T2* CMR, despite the lack of consensus studies, two different methods [subject-specific T2* (ssT2*) and absolute T2* thresholding (aT2* < 20 ms)] are interchangeably used. We examined whether these approaches yield equivalent information. METHODS: ST elevation myocardial infarction (STEMI) patients (n = 70) were prospectively recruited for CMR at 4-7 days post revascularization and for 6-month follow up (n = 43). Canines studies were performed for validation purposes, where animals (n = 20) were subject to reperfused myocardial infarction (MI) and those surviving the MI (n = 16) underwent CMR at 7 days and 8 weeks and then euthanized. Both in patients and animals, T2* of IMH and volume of IMH were determined using ssT2* and aT2* < 20 ms. In animals, ex-vivo T2* CMR and mass spectrometry for iron concentration ([Fe]Hemo) were determined on excised myocardial sections. T2* values based on ssT2* and absolute T2* threshold approaches were independently regressed against [Fe]Hemo and compared. A range of T2* cut-offs were tested to determine the optimized conditions relative to ssT2*. RESULTS: While both approaches showed many similarities, there were also differences. Compared to ssT2*, aT2* < 20 ms showed lower T2* and volume of IMH in patients and animals independent of MI age (all p < 0.005). While T2* determined from both methods were highly correlated against [Fe]Hemo (R2 = 0.9 for both), the slope of the regression curve for ssT2* was significantly larger as compared to aT2* < 20 ms (0.46 vs. 0.32, p < 0.01). Further, slightly larger absolute T2* cut-offs (patients: 23 ms; animals: 25 ms) showed similar IMH characteristics compared to ssT2*. CONCLUSION: Current quantification methods have excellent capacity to identify IMH, albeit the T2*of IMH and volume of IMH based on aT2* < 20 ms are smaller compared to ssT2*. Thus the method used to quantify IMH from T2* CMR may influence the diagnosis for IMH.


Assuntos
Imagem Cinética por Ressonância Magnética , Infarto do Miocárdio com Supradesnível do Segmento ST , Animais , Cães , Hemorragia/diagnóstico por imagem , Hemorragia/etiologia , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Miocárdio , Valor Preditivo dos Testes , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem
20.
Front Cell Dev Biol ; 9: 706832, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34422828

RESUMO

Diabetic kidney disease (DKD) is the predominant complication of diabetes mellitus (DM) and the leading cause of chronic kidney disease and end-stage renal disease worldwide, which are major risk factors for death. The pathogenesis of DKD is very complicated, including inflammation, autophagy impairment, oxidative stress, and so on. Recently, accumulating evidence suggests that the loss of mitochondrial quality control exerts critical roles in the progression of DKD. Mitochondria are essential for eukaryotic cell viability but are extremely vulnerable to damage. The mechanisms of mitochondrial quality control act at the molecular level and the organelle level, including mitochondrial dynamics (fusion and fission), mitophagy, mitochondrial biogenesis, and mitochondrial protein quality control. In this review, we summarize current knowledge of the role of disturbances in mitochondrial quality control in the pathogenesis of DKD and provide potential insights to explore how to delay the onset and development of DKD.

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