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1.
Plant Physiol ; 195(2): 1712-1727, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38401163

RESUMO

Improving nitrogen-use efficiency is an important path toward enhancing crop yield and alleviating the environmental impacts of fertilizer use. Ammonium (NH4+) is the energetically preferred inorganic N source for plants. The interaction of NH4+ with other nutrients is a chief determinant of ammonium-use efficiency (AUE) and of the tipping point toward ammonium toxicity, but these interactions have remained ill-defined. Here, we report that iron (Fe) accumulation is a critical factor determining AUE and have identified a substance that can enhance AUE by manipulating Fe availability. Fe accumulation under NH4+ nutrition induces NH4+ efflux in the root system, reducing both growth and AUE in Arabidopsis (Arabidopsis thaliana). Low external availability of Fe and a low plant Fe status substantially enhance protein N-glycosylation through a Vitamin C1-independent pathway, thereby reducing NH4+ efflux to increase AUE during the vegetative stage in Arabidopsis under elevated NH4+ supply. We confirm the validity of the iron-ammonium interaction in the important crop species lettuce (Lactuca sativa). We further show that dolomite can act as an effective substrate to subdue Fe accumulation under NH4+ nutrition by reducing the expression of Low Phosphate Root 2 and acidification of the rhizosphere. Our findings present a strategy to improve AUE and reveal the underlying molecular-physiological mechanism.


Assuntos
Compostos de Amônio , Arabidopsis , Ferro , Raízes de Plantas , Arabidopsis/metabolismo , Arabidopsis/genética , Arabidopsis/efeitos dos fármacos , Ferro/metabolismo , Compostos de Amônio/metabolismo , Glicosilação , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Lactuca/metabolismo , Lactuca/crescimento & desenvolvimento , Lactuca/genética , Nitrogênio/metabolismo , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Rizosfera , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética
2.
Biochem Biophys Res Commun ; 716: 150002, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38697011

RESUMO

Type 2 diabetes mellitus (T2DM) significantly impairs the functionality and number of endothelial progenitor cells (EPCs) and resident endothelial cells, critical for vascular repair and regeneration, exacerbating the risk of vascular complications. GLP-1 receptor agonists, like dulaglutide, have emerged as promising therapeutic agents due to their multifaceted effects, including the enhancement of EPC activity and protection of endothelial cells. This study investigates dulaglutide's effects on peripheral blood levels of CD34+ and CD133+ cells in a mouse model of lower limb ischemia and its protective mechanisms against high-glucose-induced damage in endothelial cells. Results demonstrated that dulaglutide significantly improves blood flow, reduces tissue damage and inflammation in ischemic limbs, and enhances glycemic control. Furthermore, dulaglutide alleviated high-glucose-induced endothelial cell damage, evident from improved tube formation, reduced reactive oxygen species accumulation, and restored endothelial junction integrity. Mechanistically, dulaglutide mitigated mitochondrial fission in endothelial cells under high-glucose conditions, partly through maintaining SIRT1 expression, which is crucial for mitochondrial dynamics. This study reveals the potential of dulaglutide as a therapeutic option for vascular complications in T2DM patients, highlighting its role in improving endothelial function and mitochondrial integrity.


Assuntos
Diabetes Mellitus Experimental , Células Progenitoras Endoteliais , Peptídeos Semelhantes ao Glucagon , Glucose , Fragmentos Fc das Imunoglobulinas , Dinâmica Mitocondrial , Proteínas Recombinantes de Fusão , Sirtuína 1 , Animais , Fragmentos Fc das Imunoglobulinas/farmacologia , Peptídeos Semelhantes ao Glucagon/análogos & derivados , Peptídeos Semelhantes ao Glucagon/farmacologia , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Sirtuína 1/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Masculino , Camundongos , Glucose/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Camundongos Endogâmicos C57BL , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Hipoglicemiantes/farmacologia , Humanos , Isquemia/metabolismo , Isquemia/tratamento farmacológico , Isquemia/patologia
3.
Echocardiography ; 41(5): e15834, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38784981

RESUMO

OBJECTIVES: Endocardial global longitudinal strain (endo-GLS) measured with echocardiography (echo) has been demonstrated to be associated with myocardial fibrosis (MF) and is a prognostic predictor in patients with hypertrophic cardiomyopathy (HCM). Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging showed that MF is primarily located in the myocardial layer of the extremely hypertrophic septal or ventricular wall. We hypothesized that GLS of the myocardial layer (myo-GLS) is more strongly correlated with the extent of LGE (%LGE) and is a more powerful prognostic factor than endo-GLS. METHODS: A total of 177 inpatients (54.0 [IQR: 43.0, 64.0] years, female 37.3%) with HCM were retrospectively included from May 2019 to April 2021. Among them, 162 patients underwent echocardiographic examination and contrast-enhanced CMR within 7 days. Myo-GLS and %LGE were blindly assessed in a core laboratory. All the patients were followed after they were discharged. RESULTS: During a mean follow-up of 33.77 [IQR 30.05, 35.40] months, 14 participants (7.91%) experienced major adverse cardiac events (MACE). The MACE (+) group showed lower absolute endo-GLS and myo-GLS than the MACE (-) group. Myo-GLS was more associated with %LGE (r = -.68, P < .001) than endo-GLS (r = -.64, P < .001). Cox multivariable analysis indicated that absolute myo-GLS was independently associated with MACE (adjusted hazard ratio = .75, P < .05). Myo-GLS was better than endo-GLS at detecting MACE (+) patients (-8.64%, AUC .939 vs. - 16.375%, AUC .898, P < .05). CONCLUSIONS: Myo-GLS is a stronger predictor of MACE than endo-GLS in patients with HCM and is highly correlated with %LGE.


Assuntos
Cardiomiopatia Hipertrófica , Ecocardiografia , Imagem Cinética por Ressonância Magnética , Humanos , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/fisiopatologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Imagem Cinética por Ressonância Magnética/métodos , Ecocardiografia/métodos , Adulto , Prognóstico , Valor Preditivo dos Testes , Meios de Contraste , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Seguimentos , Miocárdio/patologia , Deformação Longitudinal Global
4.
Eur Heart J ; 44(43): 4579-4588, 2023 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36994934

RESUMO

AIMS: This study aims to outline the 'true' natural history of ascending thoracic aortic aneurysm (ATAA) based on a cohort of patients not undergoing surgical intervention. METHODS AND RESULTS: The outcomes, risk factors, and growth rates of 964 unoperated ATAA patients were investigated, over a median follow-up of 7.9 (maximum of 34) years. The primary endpoint was adverse aortic events (AAE), including dissection, rupture, and aortic death. At aortic sizes of 3.5-3.9, 4.0-4.4, 4.5-4.9, 5.0-5.4, 5.5-5.9, and ≥6.0 cm, the average yearly risk of AAE was 0.2%, 0.2%, 0.3%, 1.4%, 2.0%, and 3.5%, respectively (P < 0.001), and the 10-year survival free from AAE was 97.8%, 98.2%, 97.3%, 84.6%, 80.4%, and 70.9%, respectively (P < 0.001). The risk of AAE was relatively flat until 5 cm of aortic size, at which it began to increase rapidly (P for non-linearity <0.001). The mean annual growth rate was estimated to be 0.10 ± 0.01 cm/year. Ascending thoracic aortic aneurysms grew in a very slow manner, and aortic growth over 0.2 cm/year was rarely seen. Multivariable Cox regression identified aortic size [hazard ratio (HR): 1.78, 95% confidence interval (CI): 1.50-2.11, P < 0.001] and age (HR: 1.02, 95% CI: 1.00-1.05, P = 0.015) as significant independent risk factors for AAE. Interestingly, hyperlipidemia (HR: 0.46, 95% CI: 0.23-0.91, P = 0.025) was found to be a significant protective factor for AAE in univariable Cox regression. CONCLUSION: An aortic size of 5 cm, rather than 5.5 cm, may be a more appropriate intervention criterion for prophylactic ATAA repair. Aortic growth may not be an applicable indicator for intervention.


Assuntos
Aneurisma da Aorta Torácica , Aneurisma Aórtico , Dissecção Aórtica , Ruptura Aórtica , Humanos , Dissecção Aórtica/epidemiologia , Dissecção Aórtica/cirurgia , Universidades , Aneurisma Aórtico/cirurgia , Aorta , Aneurisma da Aorta Torácica/epidemiologia , Aneurisma da Aorta Torácica/cirurgia , Fatores de Risco , Estudos Retrospectivos , Ruptura Aórtica/cirurgia
5.
Circulation ; 143(23): 2254-2272, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33663226

RESUMO

BACKGROUND: Cyanotic congenital heart disease (CCHD) is a complex pathophysiological condition involving systemic chronic hypoxia (CH). Some patients with CCHD are unoperated for various reasons and remain chronically hypoxic throughout their lives, which heightens the risk of heart failure as they age. Hypoxia activates cellular metabolic adaptation to balance energy demands by accumulating hypoxia-inducible factor 1-α (HIF-1α). This study aims to determine the effect of CH on cardiac metabolism and function in patients with CCHD and its association with age. The role of HIF-1α in this process was investigated, and potential therapeutic targets were explored. METHODS: Patients with CCHD (n=25) were evaluated for cardiac metabolism and function with positron emission tomography/computed tomography and magnetic resonance imaging. Heart tissue samples were subjected to metabolomic and protein analyses. CH rodent models were generated to enable continuous observation of changes in cardiac metabolism and function. The role of HIF-1α in cardiac metabolic adaptation to CH was investigated with genetically modified animals and isotope-labeled metabolomic pathway tracing studies. RESULTS: Prepubertal patients with CCHD had glucose-dominant cardiac metabolism and normal cardiac function. In comparison, among patients who had entered puberty, the levels of myocardial glucose uptake and glycolytic intermediates were significantly decreased, but fatty acids were significantly increased, along with decreased left ventricular ejection fraction. These clinical phenotypes were replicated in CH rodent models. In patients with CCHD and animals exposed to CH, myocardial HIF-1α was upregulated before puberty but was significantly downregulated during puberty. In cardiomyocyte-specific Hif-1α-knockout mice, CH failed to initiate the switch of myocardial substrates from fatty acids to glucose, thereby inhibiting ATP production and impairing cardiac function. Increased insulin resistance during puberty suppressed myocardial HIF-1α and was responsible for cardiac metabolic maladaptation in animals exposed to CH. Pioglitazone significantly reduced myocardial insulin resistance, restored glucose metabolism, and improved cardiac function in pubertal CH animals. CONCLUSIONS: In patients with CCHD, maladaptation of cardiac metabolism occurred during puberty, along with impaired cardiac function. HIF-1α was identified as the key regulator of cardiac metabolic adaptation in animals exposed to CH, and pubertal insulin resistance could suppress its expression. Pioglitazone administration during puberty might help improve cardiac function in patients with CCHD.


Assuntos
Cardiopatias Congênitas/patologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Miocárdio/metabolismo , Animais , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Glucose/metabolismo , Glicólise/efeitos dos fármacos , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/deficiência , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Resistência à Insulina , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miocárdio/patologia , Pioglitazona/farmacologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Puberdade , Regulação para Cima , Função Ventricular Esquerda/efeitos dos fármacos
6.
Plant Cell Environ ; 45(5): 1537-1553, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35133011

RESUMO

Rice is known for its superior adaptation to ammonium (NH4+ ) as a nitrogen source. Compared to many other cereals, it displays lower NH4+ efflux in roots and higher nitrogen-use efficiency on NH4+ . A critical role for GDP-mannose pyrophosphorylase (VTC1) in controlling root NH4+ fluxes was previously documented in Arabidopsis, but the molecular pathways involved in regulating VTC1-dependent NH4+ efflux remain unclear. Here, we report that ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1) acts as a key transcription factor regulating OsVTC1-3-dependent NH4+ efflux and protein N-glycosylation in rice grown under NH4+ nutrition. We show that OsEIL1 in rice plays a contrasting role to Arabidopsis-homologous ETHYLENE-INSENSITIVE3 (AtEIN3) and maintains rice growth under NH4+ by stabilizing protein N-glycosylation and reducing root NH4+ efflux. OsEIL1 constrains NH4+ efflux by activation of OsVTC1-3, but not OsVTC1-1 or OsVTC1-8. OsEIL1 binds directly to the promoter EIN3-binding site (EBS) of OsVTC1-3 in vitro and in vivo and acts to increase the transcription of OsVTC1-3. Our work demonstrates an important link between excessive root NH4+ efflux and OsVTC1-3-mediated protein N-glycosylation in rice grown under NH4+ nutrition and identifies OsEIL1 as a direct genetic regulator of OsVTC1-3 expression.


Assuntos
Compostos de Amônio , Arabidopsis , Oryza , Compostos de Amônio/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Glicosilação , Nitrogênio/metabolismo , Oryza/metabolismo , Raízes de Plantas/metabolismo
7.
J Card Surg ; 37(6): 1602-1610, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35348246

RESUMO

OBJECTIVE: This study aimed to establish a risk assessment model to predict postoperative severe acute lung injury (ALI) risk in patients with acute type A aortic dissection (ATAAD). METHODS: Consecutive patients with ATAAD admitted to our hospital were included in this retrospective assessment and placed in the postoperative severe ALI and nonsevere ALI groups based on the presence or absence of ALI within 72 h postoperatively (oxygen index [OI] ≤ 100 mmHg). Patients were then randomly divided into training and validation groups in a ratio of 8:2. Univariate and multivariate stepwise forward logistic regression analyses were used to statistically assess data and establish the prediction model. The prediction model's effectiveness was evaluated via 10-fold cross-validation of the validation group to facilitate the construction of a nomogram. RESULTS: After the screening, 479 patients were included in the study: 132 (27.6%) in the postoperative severe ALI group and 347 (72.4%) in the postoperative nonsevere ALI group. Based on multivariate logistics regression analyses, the following variables were included in the model: coronary heart disease, cardiopulmonary bypass (CPB) ≥ 257.5 min, left atrium diameter ≥ 35.5 mm, hemoglobin ≤ 139.5 g/L, preCPB OI ≤ 100 mmHg, intensive care unit OI ≤ 100 mmHg, left ventricular posterior wall thickness ≥ 10.5 mm, and neutrophilic granulocyte percentage ≥ 0.824. The area under the receiver operating characteristic (ROC) curve of the modeling group was 0.805 and differences between observed and predicted values were not deemed statistically significant via the Hosmer-Lemeshow test (χ2 = 6.037, df = 8, p = .643). For the validation group, the area under the ROC curve was 0.778, and observed and predicted value differences were insignificant when assessed using the Hosmer-Lemeshow test (χ2 = 3.3782, df = 7; p = .848). The average 10-fold cross-validation score was 0.756. CONCLUSIONS: This study established a prediction model and developed a nomogram to determine the risk of postoperative severe ALI after ATAAD. Variables used in the model were easy to obtain clinically and the effectiveness of the model was good.


Assuntos
Lesão Pulmonar Aguda , Dissecção Aórtica , Lesão Pulmonar Aguda/diagnóstico , Lesão Pulmonar Aguda/epidemiologia , Lesão Pulmonar Aguda/etiologia , Dissecção Aórtica/cirurgia , Humanos , Nomogramas , Período Pós-Operatório , Estudos Retrospectivos , Fatores de Risco
8.
J Card Surg ; 37(6): 1736-1739, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35362227

RESUMO

Here, we report a case of a dissected thoracoabdominal aortic aneurysm repair after frozen elephant trunk implantation, using aortic balloon occlusion technique to simplify the proximal anastomosis and avoid deep hypothermic circulatory arrest.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Oclusão com Balão , Implante de Prótese Vascular , Dissecção Aórtica/cirurgia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/métodos , Humanos
9.
Ann Plast Surg ; 89(1): 89-94, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35703215

RESUMO

BACKGROUND: The preoperative identification of perforators is critical to the success of perforator flaps. Several technologies, including handheld Doppler (HHD) and indocyanine green angiography (ICGA), facilitate this process; however, each technology comes with unique downsides. This study directly compares the performance of HHD and ICGA in preoperative perforator identification and measures the effects of flap thickness and body mass index (BMI) on perforator localization. METHOD: Data from preoperative HHD and ICGA assessments were compared with the criterion standard of intraoperative perforator localization. Sensitivity, specificity, accuracy, and positive predictive values were calculated for both and correlated with flap thickness and BMI. RESULTS: Thirty flaps were transferred in 30 patients across 15 different donor sites. Indocyanine green angiography had higher sensitivity, accuracy, and positive predictive value (79.2%, 74.2%, and 87.5%, respectively) than HHD (55.6%, 46.6%, and 69.4%, respectively). Perforators detected by ICGA were used as flap pedicles in 21 cases compared with 13 with HHD. There were no correlations between HHD or ICGA performance and patient BMI (both P > 0.05). Increasing flap thickness was negatively correlated with the accuracy of ICGA ( P = 0.001) but not HHD ( P > 0.05). CONCLUSIONS: Indocyanine green angiography was more sensitive, specific, and accurate than HHD in identifying perforators across various donor sites; however, its performance suffered in thicker flaps, whereas HHD did not. Patient BMI was not correlated with the performance of either technology. Additional research can further delineate the interrelationships of flap thickness and technologies for perforator localization.


Assuntos
Retalho Perfurante , Procedimentos de Cirurgia Plástica , Angiografia , Humanos , Verde de Indocianina , Ultrassonografia Doppler
10.
Ann Vasc Surg ; 76: 599.e7-599.e10, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33333187

RESUMO

Pulmonary artery aneurysm (PAA) is a relatively rare disease. The symptoms are usually nonspecific and often identified due to coughing or dyspnea. Pericardial tamponade caused by the PAA dissection or rupture is the most common cause of death, so active surgical treatment is recommended. The surgical reports in the literature are handful. Here we report three cases, all of whom were admitted due to exertional dyspnea. PAAs were observed from the main to the left and/or the right pulmonary artery. All three cases received PAA resection and artificial graft replacement with good outcomes.


Assuntos
Aneurisma/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Artéria Pulmonar/cirurgia , Aneurisma/diagnóstico por imagem , Aneurisma/fisiopatologia , Feminino , Humanos , Pessoa de Meia-Idade , Desenho de Prótese , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/fisiopatologia , Circulação Pulmonar , Resultado do Tratamento
11.
J Card Surg ; 36(6): 1882-1891, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33634489

RESUMO

PURPOSE: Diffuse mega-aorta is challenging. Prior studies have raised concerns regarding the safety of the open two-stage elephant trunk (ET) approach for extensive thoracic aortic aneurysm (TAA), specifically in regard to interstage mortality. This study evaluates the safety of the two-stage ET approach for management of extensive TAA. METHODS: Between 2003 and 2018, 152 patients underwent a Stage I ET procedure by a single surgeon (mean age 64.5 ± 14.8). Second stage ET procedure was planned in 60 patients (39.4%) and to-date has been performed in 54 patients (90%). (in the remaining patients, the ET was prophylactic for the long-term, with no plan for near-term utilization). RESULTS: In-hospital mortality after the Stage I procedure was 3.3% (5/152). In patients planned for Stage II, the median interstage interval was 5 weeks (range: 0-14). Of the remaining six patients with planned, but uncompleted Stage II procedures, five patients expired from various causes in the interval period (interstage mortality of 8.3%). There were no cases of aortic rupture in the interstage interval. Stage II was completed in 58 patients (including four unplanned) with a 30-day mortality of 10.3% (6/58). Seven patients developed strokes after Stage II (12%), and three patients (5.1%) developed paraplegia. CONCLUSIONS: The overall mortality, including Stage I, interstage interval, and Stage II was 18.6%. This substantial cumulative mortality for the open two-staged ET approach for the treatment of extensive TAA appears commensurate with the severity of the widespread aortic disease in this patient group. Fear of interstage rupture should not preclude the aggressive Two-Stage approach to the management of extensive TAA.


Assuntos
Aneurisma da Aorta Torácica , Ruptura Aórtica , Implante de Prótese Vascular , Idoso , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Prótese Vascular , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(5): 461-464, 2021 May 10.
Artigo em Zh | MEDLINE | ID: mdl-33974256

RESUMO

OBJECTIVE: To explore the genetic basis for a Chinese pedigree affected with X-linked hereditary Alport syndrome. METHODS: Next generation sequencing was carried out for the pedigree. Candidate variant was validated by Sanger sequencing. Pathological changes of renal basement membrane and expression of COL4A5 protein were analyzed by renal biopsy and immunofluorescence assay, respectively. RESULTS: All patients from the pedigree manifested progressive renal damage, gross hematuria, proteinuria and nephrotic syndrome. Renal biopsy of the proband revealed thickening of the basement membrane. No expression of the COL4A5 gene was detected by immunofluorescence. High-throughput sequencing and Sanger sequencing indicated that the proband has carried a c.3706delC (p.1236Pfs*69) variant in exon 41 of the COL4A5 gene. The same variant was also found in his mother and two brothers whom were similarly affected. CONCLUSION: The novel c.3706delC (p.1236Pfs*69) variant of the COL4A5 gene probably underlay the pathogenesis of X-linked hereditary Alport syndrome in this pedigree. Above findings have enriched the spectrum of COL4A5 gene variants and provided a basis for the diagnosis and genetic counseling for the pedigree.


Assuntos
Nefrite Hereditária , Colágeno Tipo IV/genética , Hematúria , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Mutação , Nefrite Hereditária/genética , Linhagem
13.
J Cell Mol Med ; 24(12): 6634-6643, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32363721

RESUMO

Sepsis-associated encephalopathy (SAE) has typically been associated with a poor prognosis. Although sestrin 2 (SESN2) plays a crucial role in metabolic regulation and the stress response, its expression and functional roles in SAE are still unclear. In the present study, SAE was established in mice through caecal ligation and puncture (CLP). The adeno-associated virus 2 (AAV2)-mediated SESN2 expression (ie overexpression and knockdown) system was injected into the hippocampi of mice with SAE, and subsequently followed by electron microscopic analysis, the Morris water maze task and pathological examination. Our results demonstrated an increase of SESN2 in the hippocampal neurons of mice with SAE, 2-16 hours following CLP. AAV2-mediated ectopic expression of SESN2 attenuated brain damage and loss of learning and memory functions in mice with SAE, and these effects were associated with lower pro-inflammatory cytokines in the hippocampus. Mechanistically, SESN2 promoted unc-51-like kinase 1 (ULK1)-dependent autophagy in hippocampal neurons through the activation of the AMPK/mTOR signalling pathway. Finally, AMPK inhibition by SBI-0206965 blocked SESN2-mediated attenuation of SAE in mice. In conclusion, our findings demonstrated that SESN2 might be a novel pharmacological intervention strategy for SAE treatment through promotion of ULK1-dependent autophagy in hippocampal neurons.


Assuntos
Autofagia , Hipocampo/patologia , Neurônios/metabolismo , Neurônios/patologia , Peroxidases/metabolismo , Encefalopatia Associada a Sepse/metabolismo , Encefalopatia Associada a Sepse/patologia , Adenilato Quinase/metabolismo , Animais , Autofagossomos/metabolismo , Autofagossomos/ultraestrutura , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Feminino , Camundongos Endogâmicos C57BL , Peroxidases/genética , Encefalopatia Associada a Sepse/genética , Encefalopatia Associada a Sepse/prevenção & controle , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima/genética
14.
Bioorg Chem ; 95: 103457, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31901757

RESUMO

OBJECTIVES: The influences of COL1A1 and MZB1 on the proliferation, migration, invasion and apoptosis abilities of rectum adenocarcinoma was aimed to explore in this study. METHODS: Gene expression levels in rectum adenocarcinoma and adjacent tissues were analyzed by differential analysis. Weighted gene correlation network analysis (WGCNA) was employed to investigate rectal adenocarcinoma (READ) hub genes. MCODE was performed to screen the modules of protein-protein interaction network in Cytoscape software. Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool is considered to be the most effective tool in gene ontology (GO) enrichment and Kyoto Gene and Genomics Encyclopedia (KEGG) pathway analysis. Survival analysis was performed using READ patient information from TCGA-READ project database. Quantitative Real-time Polymerase Chain Reaction (qRT-PCR) and western blot were employedto examinemRNA and protein expressions of COL1A1 and MZB1 in tumor tissues and cell lines. After transfecting various interference sequences by liposome-mediated transfection, the influence of COL1A1 and MZB1 on the proliferation, apoptosis, migration and invasion of rectal cancer cells were observed by plate clone formation assay, flow cytometry, wound healing assay and transwell assay respectively. Moreover, xenograft tumor growth assay in vivo validated the results. RESULTS: Higher expression levels of COL1A1 and lower expression levels of MZB1 were discovered in tumor tissues of patients with colorectal adenocarcinoma. Overexpression of MZB1 and silencing COL1A1 significantly inhibited proliferation, migration and invasion, while cell apoptosis was promoted. Overexpression of MZB1 and silencing COL1A1 inhibited the orthotopic growth of tumor in vivo. CONCLUSION: COL1A1 promoted proliferation, migration and invasion but inhibited apoptosis of rectal adenocarcinoma cells while MZB1 was totally on the contrary.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Apoptose/genética , Colágeno Tipo I/genética , Adenocarcinoma , Movimento Celular/genética , Proliferação de Células/genética , Cadeia alfa 1 do Colágeno Tipo I , Humanos , Neoplasias Retais , Células Tumorais Cultivadas
15.
17.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(11): 1233-1235, 2020 Nov 10.
Artigo em Zh | MEDLINE | ID: mdl-33179227

RESUMO

OBJECTIVE: To detect variants of ADAR1 gene in two Chinese pedigrees affected with dyschromatosis symmetrica hereditaria (DSH). METHODS: Clinical data and peripheral blood samples of the pedigrees were collected. All exons of the ADAR1 gene were amplified by PCR and subjected to Sanger sequencing. Suspected pathogenic variants were validated among other members of the pedigrees and 100 unrelated healthy controls. RESULTS: For pedigree 1, Sanger sequencing has identified a heterozygous missense variant c.3002G>C (p.Asp968His) in exon 11 of the ADAR1 gene in the proband and his father. For pedigree 2, a novel nonsense variant c.3145C>T (p.Gln1049Ter) was identified in exon 12 of the ADAR1 gene in the proband and his son, which were previously unreported and absent among the healthy controls. CONCLUSION: The c.3002G>C (p.Asp968His) and c.3145C>T (p.Gln1049Ter)variants of the ADAR1 gene probably underlay the DSH in the two pedigrees.


Assuntos
Adenosina Desaminase/genética , Transtornos da Pigmentação/congênito , Proteínas de Ligação a RNA/genética , Humanos , Mutação , Linhagem , Transtornos da Pigmentação/genética
18.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(12): 1368-1370, 2020 Dec 10.
Artigo em Zh | MEDLINE | ID: mdl-33306824

RESUMO

OBJECTIVE: To detect pathological variants of the SLC12A3 gene in a Chinese pedigree affected with Gitelman syndrome (GS). METHODS: Clinical data and peripheral blood samples of the proband and his family members were collected. All exons of the SLC12A3 gene were amplified by PCR and subjected to Sanger sequencing. RESULTS: Sanger sequencing has revealed that the proband has carried a c.486_489 delTACG (p.Ile162Met fs*8) deletion and a heterozygous c.2890C>T (p.Arg964Trp) missense variant in the SLC12A3 gene. Neither variant was reported previously and was not found among healthy controls. CONCLUSION: The c.486_489delTACG (p.Ile162Met fs*8) and c.2890C>T (p.Arg964Trp) variants of the SLC12A3 gene probably underlay the GS in the proband. Above discovery has enriched the variant spectrum of GS.


Assuntos
Síndrome de Gitelman , China , Síndrome de Gitelman/genética , Heterozigoto , Humanos , Mutação/genética , Linhagem , Membro 3 da Família 12 de Carreador de Soluto/genética
19.
J Vasc Surg ; 70(6): 2046-2053.e6, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31204217

RESUMO

OBJECTIVE: Isolated abdominal aortic dissection (IAAD) has remained poorly understood because of its rarity. We explored the prevalence, clinical characteristics, risk factors, imaging characteristics, and treatment strategy of IAAD to facilitate its diagnosis and treatment. METHODS: We performed a meta-analysis of 17 studies, with single-arm-based and network meta-analysis as the main data synthesis method. The Medline, Embase, and Cochrane library were searched from their inception to July 2018. A total of 9163 patients with aortic disease were enrolled, with IAAD identified in 491 patients. RESULTS: The pooled prevalence of IAAD among cases of aortic dissection overall, type B aortic dissection, and type A aortic dissection was 1.7% (95% confidence interval [CI], 0.9%-3.4%), 4.1% (95% CI, 2.5%-6.6%), and 2.0% (95% CI, 0.7%-3.9%), respectively. Abdominal pain was the most common symptom (50.8%), followed by back pain (30.5%), and chest pain (21.7%). Up to 41.0% of the patients with IAAD did not present with any clinical symptoms, and up to 71.0% of these patients had negative findings on physical examination. The top three most prevalent risk factors for IAAD were hypertension, hyperlipidemia, and smoking. Most cases of IAAD were limited to the aorta inferior to the renal arteries (81.7%), and the average aortic diameter was 4 cm. No statistically significant difference was observed between open surgery, endovascular aortic repair, and conservative management for both early and late mortality. CONCLUSIONS: The results from the present meta-analysis regarding IAAD support the following conclusions and recommendations. First, IAAD is rare and predominantly affects males. Second, symptoms (pain) might or might not be present, and physical findings will rarely be found on abdominal examination. Third, hypertension is the most prevalent risk factor. Fourth, most cases IAAD will be infrarenal. Finally, a complication-specific approach, similar to that for type B aortic dissection, would be appropriate.


Assuntos
Aneurisma da Aorta Abdominal/diagnóstico , Aneurisma da Aorta Abdominal/terapia , Dissecção Aórtica/diagnóstico , Dissecção Aórtica/terapia , Dissecção Aórtica/epidemiologia , Aneurisma da Aorta Abdominal/epidemiologia , Humanos , Prevalência , Fatores de Risco
20.
J Card Surg ; 34(12): 1563-1568, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31705825

RESUMO

BACKGROUND: Paraplegia is adevastating complication of open descending (DTAA) and thoracoabdominal aortic aneurysm (TAAA) repair. Despite major advances in imaging and surgical techniques, paraplegia continues to be problematic. We present our experience with routine application of enhanced imaging techniques to detect the anterior spinal artery (ASA) before DTAA and TAAA repair. METHODS: We retrospectively reviewed 177 patients with DTAA and TAAA who underwent imaging to detect the ASA before open surgical repair. High definition CT angiography (CTA) and dual energy CT scanning (DECT) were our modalities of choice with angiography used earlier and magnetic resonance angiography (MRA) used when CT was contraindicated. Descriptive statistics and χ2 analyses were conducted. RESULTS: The imaging protocol successfully detected the level of the ASA in 132 (74.5%) patients, utilizing CTA in 67, DECT in 28, spinal angiography in 31, and MRA in 6. Cross sectional modalities with advanced visualization technique (CT, DECT, and MRA) were more successful at detecting the ASA than angiography (80.72%, 82.35%, 75% vs 59.62%, respectively, P = .04). Concerted efforts were made not to leave the operating room without continuity of the ASA with the circulation (via limited resection, beveled anastomosis, or reimplantation). Transient lower extremity weakness was observed in 11 (6.2%) patients, and permanent paraplegia in 2 (1.12%) patients. CONCLUSION: Modern imaging technology provides multiple methodologies highly successful at detecting the ASA. The ASA can then be preserved intraoperatively, contributing to low paraplegia rates. We strongly recommend routine application of this technology to arm the surgeon with precise information about the specific patient's spinal cord blood supply.


Assuntos
Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Medula Espinal/irrigação sanguínea , Medula Espinal/diagnóstico por imagem , Adulto , Idoso , Feminino , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Paraplegia/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Estudos Retrospectivos , Isquemia do Cordão Espinal/prevenção & controle , Tomografia Computadorizada por Raios X
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