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2.
J Vasc Surg ; 80(1): 153-162.e4, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38460766

RESUMO

OBJECTIVE: Selection criteria for carotid duplex ultrasonography screening (DUS) before coronary artery bypass grafting (CABG) is primarily based on limited observational analysis, and the risks associated with carotid artery stenosis (CAS) detected by this approach to preoperative DUS are uncertain. This study aimed to determine the association of carotid DUS with stroke and mortality among patients undergoing CABG. METHODS: Adult patients with coronary artery disease who underwent isolated CABG or CABG with concomitant valvular or congenital procedure were identified. CHA2DS2-VASc score was assessed before CABG, and patients were recorded as high risk if they had a score of 3 or higher. The primary outcomes were stroke and all-cause mortality. Secondary outcomes included ischemic stroke, non-ischemic stroke, transient ischemic attack, and cardiovascular mortality. RESULTS: Among 8958 patients who underwent CABG, 70.9% (n = 6347) received carotid DUS preoperatively (low-risk, 57.3%; high-risk, 42.7%). In the low-risk cohort, there was no significant difference in the risk of stroke (20.7 per 1000 patient-years for CAS vs 13.1 per 1000 patient-years for no CAS; adjusted hazard ratio [aHR], 1.14; 95% confidence interval [CI], 0.78-1.68) or mortality (20.5 per 1000 patient-years for CAS vs 16.8 per 1000 patient-years for no CAS; aHR, 1.33; 95% CI, 0.97-1.83) at 15 years. In the high-risk cohort, CAS was associated with significantly higher risks of stroke at 30 days (433.2 vs 279.5 per 1000 patient-years; aHR, 1.92; 95% CI, 1.00-3.70) and mortality at 15 years (38.4 vs 32.7 per 1000 patient-years; aHR, 1.25; 95% CI, 1.01-1.57) compared with no CAS. CONCLUSIONS: CAS did not impact the incidence of stroke or mortality in the low-risk cohort who underwent CABG. However, in the high-risk cohort, CAS was associated with a significant increase in the risks of 30-day stroke and 15-year mortality, indicating selective carotid DUS is necessarily recommended for these patients.


Assuntos
Estenose das Carótidas , Ponte de Artéria Coronária , Doença da Artéria Coronariana , Valor Preditivo dos Testes , Acidente Vascular Cerebral , Ultrassonografia Doppler Dupla , Humanos , Masculino , Feminino , Ponte de Artéria Coronária/mortalidade , Ponte de Artéria Coronária/efeitos adversos , Idoso , Medição de Risco , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/mortalidade , Estenose das Carótidas/complicações , Estenose das Carótidas/cirurgia , Pessoa de Meia-Idade , Fatores de Risco , Estudos Retrospectivos , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/etiologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/cirurgia , Doença da Artéria Coronariana/complicações , Resultado do Tratamento , Fatores de Tempo
3.
Plant Physiol ; 195(2): 1461-1474, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38431527

RESUMO

Black goji berry (Lycium ruthenicum Murray) contains a rich source of health-promoting anthocyanins which are used in herbal medicine and nutraceutical foods in China. A natural variant producing white berries allowed us to identify two key genes involved in the regulation of anthocyanin biosynthesis in goji berries: one encoding a MYB transcription factor (LrAN2-like) and one encoding a basic helix-loop-helix (bHLH) transcription factor (LrAN1b). We previously found that LrAN1b expression was lost in the white berry variant, but the molecular basis for this phenotype was unknown. Here, we identified the molecular mechanism for loss of anthocyanins in white goji berries. In white goji, the LrAN1b promoter region has a 229 bp deletion that removes three MYB-binding elements and one bHLH-binding element, which are key to its expression. Complementation of the white goji berry LrAN1b allele with the LrAN1b promoter restored pigmentation. Virus-induced gene silencing of LrAN1b in black goji berry reduced fruit anthocyanin biosynthesis. Molecular analyses showed that LrAN2-like and another bHLH transcription factor LrJAF13 can activate LrAN1b by binding directly to the MYB-recognizing element and bHLH-recognizing element of its promoter-deletion region. LrAN1b expression is enhanced by the interaction of LrAN2-like with LrJAF13 and the WD40 protein LrAN11. LrAN2-like and LrAN11 interact with either LrJAF13 or LrAN1b to form two MYB-bHLH-WD40 complexes, which hierarchically regulate anthocyanin biosynthesis in black goji berry. This study on a natural variant builds a comprehensive anthocyanin regulatory network that may be manipulated to tailor goji berry traits.


Assuntos
Antocianinas , Fatores de Transcrição Hélice-Alça-Hélice Básicos , Frutas , Regulação da Expressão Gênica de Plantas , Lycium , Proteínas de Plantas , Regiões Promotoras Genéticas , Antocianinas/biossíntese , Antocianinas/metabolismo , Regiões Promotoras Genéticas/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Frutas/genética , Frutas/metabolismo , Lycium/genética , Lycium/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Deleção de Sequência , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
4.
Br J Pharmacol ; 181(8): 1182-1202, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37949672

RESUMO

BACKGROUND AND PURPOSE: Kaempferol-3-O-sophoroside (PCS-1) is the main component in Crocus sativus (Saffron), a herb with mood-enhancing properties. AMP-activated protein kinase (AMPK) is a potential therapeutic target for depression. This study explores the antidepressive-like properties of PCS-1 and its AMPK activation to confirm AMPK as a target for antidepression. EXPERIMENTAL APPROACH: Corticosterone (CORT)-induced PC12 cell injury served as an in vitro model to evaluate the neuroprotective effect of PCS-1. Neuro-2a cells and primary neurons were utilized to evaluate the synaptogenesis role of PCS-1. CORT-induced mouse depression model and chronic unpredictable mild stress (CUMS) model were used to assess the antidepressive-like properties of PCS-1 through behavioural tests, magnetic resonance imaging, and biochemical index measurements. Western blot and immunofluorescence assays were used to study the mechanisms of PCS-1. Cellular thermal shift assay was used to confirm the binding target. KEY RESULTS: PCS-1 (12.5-50 µM) ameliorated CORT-induced PC12 cell damage, oxidative stress and inflammation. PCS-1 alone promoted an increase in synapses in Neuro-2a cells and primary neurons. Oral administration of PCS-1 (10 and 20 mg·kg-1 ) ameliorated weight loss, dyskinesia, and hippocampal volume reduction induced by CORT and CUMS. PCS-1 bound to AMPK to improve the expression of brain-derived neurotrophic factor (BDNF) and induce autophagy. CONCLUSION AND IMPLICATIONS: PCS-1 binds to AMPK to promote BDNF production and autophagy enhancement, ultimately achieving antidepressant effects. This study provides support for the clinical application of saffron petals and provides further evidence for AMPK as a potential target for antidepression.


Assuntos
Proteínas Quinases Ativadas por AMP , Depressão , Camundongos , Animais , Depressão/tratamento farmacológico , Depressão/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Camundongos Endogâmicos C57BL , Quempferóis/farmacologia , Quempferóis/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Antidepressivos/metabolismo , Hipocampo/metabolismo , Estresse Psicológico/tratamento farmacológico , Estresse Psicológico/metabolismo , Modelos Animais de Doenças
5.
Genes (Basel) ; 14(7)2023 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-37510286

RESUMO

Cervical cancer is the fourth most common cancer. The 5-year survival rate for metastatic cervical cancer is less than 10%. The survival time of patients with recurrent cervical cancer is approximately 13-17 months. Cuproptosis is a novel type of cell death related to mitochondrial respiration. Accumulative studies showed that long non-coding RNAs (lncRNAs) regulated cervical cancer progression. Compressive bioinformatic analysis showed that nine cuproptosis-related lncRNAs (CRLs), including C002128.2, AC002563.1, AC009237.14, AC048337.1, AC145423.1, AL117336.1, AP001542.3, ATP2A1-AS1, and LINC00426, were independently correlated with the overall survival (OS) of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) patients. The time-dependent area under curve value reached 0.716 at 1 year, 0.718 at 3 years, and 0.719 at 5 years. Notably, CESC patients in the low-risk group had increased immune cell infiltration and expression of several immune checkpoints, which indicated that they may benefit more from immune checkpoint blockade therapy. In addition, we also used the model for drug sensitivity analysis. Several drug sensitivities were more sensitive in high-risk patients and showed significant correlations with the risk models, such as Bortezomib_1191, Luminespib_1559, and Rapamycin_1084, suggesting that these drugs may be candidate clinical drugs for patients with a high risk of CESC. In summary, this study further explored the mechanism of CRLs in CESC and provided a more optimized prognostic model and some insights into chemotherapy of CESC.


Assuntos
Adenocarcinoma , Apoptose , Carcinoma de Células Escamosas , RNA Longo não Codificante , Neoplasias do Colo do Útero , Feminino , Humanos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Recidiva Local de Neoplasia , Prognóstico , RNA Longo não Codificante/genética , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/genética , Cobre
6.
J Ovarian Res ; 16(1): 47, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36859398

RESUMO

Curcumin, a natural organic component obtained from Curcuma longa's rhizomes, shows abundant anti-tumor, antioxidant and anti-inflammatory pharmacological activities, among others. Notably the anti-tumor activity has aroused widespread attention from scholars worldwide. Numerous studies have reported that curcumin can delay ovarian cancer (OC), increase its sensitivity to chemotherapy, and reduce chemotherapy drugs' side effects. It has been shown considerable anticancer potential by promoting cell apoptosis, suppressing cell cycle progression, inducing autophagy, inhibiting tumor metastasis, and regulating enzyme activity. With an in-depth study of curcumin's anti-OC mechanism, its clinical application will have broader prospects. This review summarizes the latest studies on curcumin's anti-OC activities, and discusses the specific mechanism, hoping to provide references for further research and applications.


Assuntos
Curcumina , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias Ovarianas , Feminino , Humanos , Antioxidantes , Apoptose , Autofagia
7.
Pharmacol Res ; 178: 106182, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35304259

RESUMO

Ischemic stroke is one of the leading causes of death and disability worldwide. The severe sequelae caused by ischemic thrombolysis and the narrow time window are now the main clinical challenges. Our previous study has reported 4-Trifluoromethyl-(E)-cinnamoyl]-L-4-F-phenylalanine Acid (AE-18) was a promising candidate for Parkinson's Disease. In this study, the preventive and therapeutic effects of AE-18 on focal cerebral ischemia-reperfusion injury and the mechanisms are explored. In oxygen glucose deprivation/reoxygenation (OGD/R)-induced well-differentiated PC12 cells model, AE-18 (10 or 20 µM) can significantly reduce nerve damage when administered before or after molding. In middle cerebral artery occlusion-reperfusion (MCAO/R) rat model, pre-modelling, or post-modelling administration of AE-18 (5 or 10 mg/kg) was effective in reducing neurological damage, decreasing infarct volume and improving motor disturbances. In addition, AE-18 (5 mg/kg) given by intravenous injection immediately after occlusion significantly reduce the infarct volume caused by reperfusion for different durations, indicating that AE-18 could extend the time window of thrombolytic therapy. Further studies demonstrate that AE-18 exerts the effects in the prevention, treatment, and prolongation of the time window of cerebral ischemic injury mainly through inhibiting excitotoxicity and improving BBB permeability, VEGF and BDNF. These results suggest that AE-18 is a good candidate for the treatment of ischemic stroke.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Fármacos Neuroprotetores , Fenilalanina , Traumatismo por Reperfusão , Animais , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Isquemia/complicações , Fármacos Neuroprotetores/uso terapêutico , Fenilalanina/farmacologia , Fenilalanina/uso terapêutico , Ratos , Reperfusão/efeitos adversos , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/prevenção & controle
8.
Phytomedicine ; 95: 153880, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34906892

RESUMO

BACKGROUND: Chemotherapy-induced thrombocytopenia (CIT) is a severe adverse drug reaction, and the main reason for CIT is the destruction of megakaryocytes (MKs, precursor cells of platelet) in bone marrow by chemotherapy. Peanut skin, the seed coat of Arachis hypogaea L., is a traditional Chinese medicine commonly used to treat thrombocytopenia. However, its active compounds and the mechanisms remain unclear. PURPOSE: This study aims to clarify the active compounds of peanut skin to exhibit thrombogenic effects against CIT and their underlying mechanisms in vitro and in vivo. STUDY DESIGN: The bioassay-guided isolation based on the proliferation of MKs was used to explore the possible platelet-enhancing ingredients in peanut skin. HSCCC technique coupled with preparative HPLC was used to separate the active compounds. Dami cells and carboplatin-treated mice model were used to evaluate the thrombogenic effects of PS-1. Network pharmacology, molecular docking, dynamics simulation studies, kinase activity, surface plasmon resonance (SPR), cellular thermal shift assay (CETSA), isothermal dose-response fingerprint (ITDRFCETSA) and western blot analysis were performed to investigate the mechanisms of PS-1. RESULTS: Proanthocyanidin A1 (PS-1) and its stereoisomers (PS-2-4) were demonstrated to promote the proliferation of MKs (Dami cells), especially PS-1 (EC50 = 8.58 µM). Further studies demonstrated that PS-1 could induce the differentiation of Dami cells in dose/time-dependent manner. Biological target analysis showed that PS-1 directly bound to JAK2 (KD = 2.06 µM) to exert potent activating effect (EC50 = 0.66 µM). Oral administration of PS-1 (25 or 50 mg/kg) significantly improved CIT, but this effect was confirmed to be inhibited by JAK2 inhibitor AG490, indicating that PS-1 exerted its efficacy through JAK2 in vivo. CONCLUSION: Proanthocyanins (PS-1-4) derived from peanut skin were first clarified as platelet-enhancing ingredients to improve CIT. The underlying mechanism of PS-1 was proved to promote the proliferation and differentiation of MKs via JAK2/STAT3 pathway both in vitro and in vivo.


Assuntos
Antineoplásicos , Trombocitopenia , Animais , Plaquetas , Janus Quinase 2/metabolismo , Camundongos , Simulação de Acoplamento Molecular , Farmacologia em Rede , Proantocianidinas , Fator de Transcrição STAT3/metabolismo , Trombocitopenia/induzido quimicamente , Trombocitopenia/tratamento farmacológico
9.
Eur Heart J Cardiovasc Imaging ; 23(8): 1018-1026, 2022 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34718482

RESUMO

AIMS: Many factors cause left ventricular outflow tract obstruction (LVOTO) in hypertrophic cardiomyopathy (HCM). Previous studies reported that left ventricular basal muscle bundle (BMB) may be associated with LVOTO. We aimed to evaluate the role of BMB in LVOTO by echocardiography. METHODS AND RESULTS: Two hundred fifty-six patients diagnosed with HCM were recruited. The morphologic characteristics of left ventricular outflow tract (LVOT) were analysed. BMB was detected in 178 (69.5%) patients by echocardiography. Patients were separated by a resting or provocative LVOT gradient ≥30 mmHg or not. Compared to patients without LVOTO, patients with LVOTO had a significantly thicker basal septum, elongated anterior mitral leaflet (AML), shorter distance between the AML-free margin and the septum or BMB (M-sept/bundle), larger angle between the plane of the mitral valvular orifice and the ascending aorta (MV-AO angle), and higher prevalence of BMB (P < 0.05). According to multivariate analysis, the independent predictors of LVOTO were the presence of BMB, a large basal septum thickness, a short M-sept/bundle, a large MV-AO angle, and a large AML [odds ratio (95% confidence interval): 5.207 (1.381-19.633), 1.386(1.141-1.683), 0.615(0.499-0.756), 1.113(1.054-1.176), and 1.343(1.076-1.677), respectively, P < 0.05]. Of the 256 included patients, 139 underwent surgical myectomy. The transthoracic echocardiography, compared with surgical specimen, showed: sensitivity 98.3%, specificity 82.3%, positive predictive value 97.6%, negative predictive value 87.5%, and accuracy 96.4% to detect BMB. CONCLUSIONS: BMB is common in HCM. BMB is a risk factor for LVOTO.


Assuntos
Cardiomiopatia Hipertrófica , Cardiopatias Congênitas , Obstrução do Fluxo Ventricular Externo , Cardiopatias Congênitas/complicações , Ventrículos do Coração/diagnóstico por imagem , Humanos , Valva Mitral/cirurgia , Músculos
10.
Front Cardiovasc Med ; 8: 695536, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34386530

RESUMO

Aims: This study aimed to investigate the pathology, classification, diagnosis, and surgical prognosis of UCMV. Methods and Results: Consecutive paediatric patients with ≥ moderate-severe mitral regurgitation (MR) and mitral stenosis (MS) were recruited between October 2016 and July 2020. UCMV was diagnosed and classified into three grades according to the involvement of chorda groups and MS presence or absence; other mitral lesions were included as controls. Of 207 eligible patients, 75 with UCMV (10.0 m [interquartile range (IQR): 6.0-21.5]) and 110 with other mitral lesions (16.0 m [IQR: 5.0-43.5]) were diagnosed using echocardiography and surgical exploration. The associated chorda groups of UCMV were confirmed to show high agreement between echocardiography and surgery (kappa = 0.857, p < 0.001). At baseline surgery assessment, the UCMV group exhibited worse New York Heart Association functional class, more severe MR and MS grades, and fewer associated complex anomalies (all, p < 0.05) than the control group. After a mean follow-up of 8.3 (IQR:2.7-14.4) months and adjustment for covariates, the UCMV group required longer cardiopulmonary bypass and aortic clamp times, but there were no differences in the incidence of adverse events (p = 0.584). Class III was associated with higher risk of adverse events than classes I and II (p = 0.002). Conclusions: The UCMV spectrum constitutes a primary pathogenesis of paediatric MV dysfunction, which can be optimally diagnosed using echocardiography. Classification based on mitral anatomy and dysfunction can predict the risk of postoperative adverse events.

11.
Eur J Cardiothorac Surg ; 59(6): 1312-1319, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-33759999

RESUMO

OBJECTIVES: The purpose of this study was to review the outcomes of surgical treatment in patients with aorto-left ventricular tunnel and to investigate what kind of patient cohort is more likely to have adverse events. METHODS: Twenty-one patients with a median age of 6.58 [interquartile range (IQR) 4.17-24.50] years who received surgical treatment of aorto-left ventricular tunnel from March 2002 to December 2019 were reviewed. The median follow-up time was 64.50 (IQR 25.15-120.50) months. Clinical characteristics, surgical methods and follow-up outcomes were summarized in separate groups of patients with or without preoperative aortic valve (AoV) issues. Composite adverse events were defined as death or requirement of reoperation. Time-related analysis of freedom from death and requirement of reoperation was performed with the Kaplan-Meier method. RESULTS: The average tunnel size was 8.68 (standard deviation: 3.62) mm. The most common and the most important associated lesions were AoV lesions. Tunnels in 20 patients were closed with direct sutures or a patch. For 1 patient with an irreparable AoV, the tunnel was cut open simultaneously with aortic valve replacement and aortic root plasty. In the group of patients with preoperative AoV issues, 4 patients received aortic valve replacement with mechanical prosthetic valves and 6 patients received aortic valvuloplasty repair. The follow-up outcomes differed significantly between groups (the incidence of death was 15.38% and the incidence of requiring a reoperation was 46.15% in patients with preoperative AoV issues). In the group without preoperative AoV issues, there were no deaths and no reoperations (Fisher's exact test; P = 0.018). The probability of freedom from death and of the requirement for reoperation between the 2 groups was not significantly different (log-rank, P = 0.09). Overall, the estimated probability of freedom from death and requirement of reoperation was 77.30% (standard error: 10.20%) [95% confidence interval (CI): 49.53-91.00] at 5 years, 67.64% (standard error: 12.70%) (95% CI: 36.71-85.84) at 10 years. CONCLUSIONS: Patients with aorto-left ventricular tunnel with preoperative AoV issues are more prone to die or to require a reoperation. In contrast, patients without preoperative AoV issues can be free from death or reoperation for a longer period of time. Patients with preoperative AoV issues need much stricter postoperative long-term echocardiographic follow-up.


Assuntos
Insuficiência da Valva Aórtica , Estenose da Valva Aórtica , Túnel Aorticoventricular , Próteses Valvulares Cardíacas , Adolescente , Adulto , Valva Aórtica , Insuficiência da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Criança , Pré-Escolar , Humanos , Reoperação , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Front Plant Sci ; 11: 1256, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32922426

RESUMO

Lycium ruthenicum Murry. is a highly nutritional cash crop due to its fruit abundant anthocyanins. To understand the complex metabolic networks underlying the color formation in black and white fruits of L. ruthenicum, we conducted transcriptome and flavonoid metabolic profiling to identify the candidate genes possibly involved in flavonoid biosynthesis. As a result, 147 flavonoids were identified and there was almost no anthocyanin in white fruits, while luteolin, kaempferol, and quercetin derivatives showed markedly higher abundance. Furthermore, applying weighted gene co-expression network analyses, 3 MYB, 2 bHLH, 1WRKY and 1 NAC transcription factor, associated with anthocyanin biosynthesis were identified. A bHLH transcription factor, LrAN1b showed the greatest correlations with anthocyanin accumulation with no expression in white fruits. In addition, gene function analysis and qRT-PCR experiments identified a new activated anthocyanin MYB transcription factor designed as LrAN2-like. Yeast two-hybrid and transient tobacco overexpression experiments showed that LrAN1b could interact with LrAN2-like and LrAN11 to form MBW complex to activate the anthocyanin pathway. The yeast one-hybrid experiment indicated that LrAN2-like bonded anthocyanin structural gene LrDFR and LrANS promoters. Heterologous expression of LrAN1b in tobacco can significantly increase the anthocyanin content of tobacco florals and capsules, and activate anthocyanin synthesis related genes. Taken together, an anthocyanin regulatory network model in L. ruthenicum fruit was proposed firstly and we speculate that the white fruit phenotype was due to abnormal expression of LrAN1b. The findings provide new insight into the underlying mechanism of flavonoids, laying the foundation for future functional and molecular biological research in L. ruthenicum.

13.
Mol Neurobiol ; 57(11): 4628-4641, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32770451

RESUMO

Parkinson's disease (PD) is a common neurodegenerative disorder primarily caused by the death of dopaminergic neurons in the substantia nigra pars compacta (SNpc). However, the manner of death of dopaminergic neurons remains indistinct. Ferroptosis is a form of cell death involving in the iron-dependent accumulation of glutathione depletion and lipid peroxide. Besides, previous studies indicated that ferroptosis might be involved in the death of dopaminergic neurons. In this study, we aim to explore the protective effect of the p62-Keap1-Nrf2 pathway against 6-hydroxydopamine (6-OHDA)-induced ferroptosis in dopaminergic cells. Firstly, our results demonstrated that 6-OHDA-induced ferroptosis could be observed in vivo zebrafish and in vitro human dopaminergic cell line (SH-SY5Y cells) model. Moreover, ferroptosis induced by 6-OHDA mitigates in SH-SY5Y cells upon ferrostatin-1 (Fer, an inhibitor of ferroptosis) treatment via upregulating the protein expression of glutathione peroxidase 4 (GPX4). Then, we found that high p62/SQSTM1 (p62) expression could protect SH-SY5Y cells against ferroptosis through promoting Nrf2 nuclear transfer and upregulating the expression of the antioxidant protein heme oxygenase-1 (HO-1). Ultimately, high p62 expression activates the Nrf2/HO-1 signaling pathway through binding to Kelch-like ECH-associated protein 1 (Keap1). Collectively, the activation of the p62-Keap1-Nrf2 pathway prevents 6-OHDA-induced ferroptosis in SH-SY5Y cells, targeting this pathway in combination with a pharmacological inhibitor of ferroptosis can be a potential approach for PD therapy.


Assuntos
Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Ferroptose , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Neuroproteção , Proteína Sequestossoma-1/metabolismo , Transdução de Sinais , Animais , Linhagem Celular , Cicloexilaminas/farmacologia , Neurônios Dopaminérgicos/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Modelos Biológicos , Neuroproteção/efeitos dos fármacos , Oxidopamina , Fenilenodiaminas/farmacologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Ligação Proteica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Peixe-Zebra
14.
J Geriatr Cardiol ; 17(12): 766-774, 2020 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33424944

RESUMO

BACKGROUND: The effective orifice area (EOA) is utilized to characterize the hemodynamic performance of the transcatheter heart valve (THV). However, there is no consensus on EOA measurement of self-expanding THV. We aimed to compare two echocardiographic methods for EOA measurement following transcatheter self-expanding aortic valve implantation. METHODS: EOA was calculated according to the continuity equation. Two methods were constructed. In Method 1 and Method 2, the left ventricular outflow tract diameter (LVOTd) was measured at the entry of the prosthesis (from trailing-to-leading edge) and proximal to the prosthetic valve leaflets (from trailing-to- leading edge), respectively. The velocity-time integral (VTI) of the LVOT (VTILVOT) was recorded by pulsed-wave Doppler (PW) from apical windows. The region of the PW sampling should match that of the LVOTd measurement with precise localization. The mean transvalvular pressure gradient (MG) and VTI of THV was measured by Continuous wave Doppler. RESULTS: A total of 113 consecutive patients were recruited. The mean age was 77.2 ± 5.5 years, and 72 patients (63.7%) were male. EOA1 with the use of Method 1 was larger than EOA2 (1.56 ± 0.39 cm2 vs. 1.48 ± 0.41 cm2, P = 0.001). MG correlated better with the indexed EOA1 (EOAI1) (r = -0.701, P < 0.001) than EOAI2 (r = -0.645, P < 0.001). According to EOAI (EOAI ≤ 0.65 cm2/m2, respectively), the proportion of sever prosthesis-patient mismatch with the use of EOA1 was lower than EOA2 (12.4% vs. 21.2%, P < 0.05). Compared with EOA2, EOA1 had lower interobserver and intra-observer variability (intra: 0.5% ± 17% vs. 3.8% ± 22%, P < 0.001; inter: 1.0% ± 9% vs. 3.5% ± 11%, P < 0.001). CONCLUSIONS: For transcatheter self-expanding valve EOA measurement, LVOTd should be measured in the entry of the prosthesis stent (from trailing-to-leading edge), and VTILVOT should match that of the LVOTd measurement with precise localization.

15.
Mol Genet Genomics ; 294(5): 1241-1249, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31104103

RESUMO

Hypertrophic cardiomyopathy (HCM), a major cause of sudden death in youth, is largely affected by genetic factors. The R58Q mutation in the MYL2 gene was identified in some HCM patients and was considered as a deleterious HCM mutation. However, the passing of R58Q between generations along with HCM symptoms was observed only in small families with only two or three members; thus, whether R58Q is as deleterious as previously claimed remains questionable. Here, we reported a large four-generation Chinese family, and found that R58Q existed in all six members with HCM and two healthy juveniles who had not yet developed HCM yet, and presumably in three deceased members who suffered from sudden death. In addition, we also found that compared with other mutations, R58Q had a more severe effect on the cellular level. Therefore, we confirmed that R58Q could be passed from generation to generation along with HCM symptoms and that it was indeed a deleterious mutation for HCM. However, further study is needed to identify additional factors that may determine the various symptoms shown in different family members within the same family.


Assuntos
Povo Asiático/genética , Cardiomiopatia Hipertrófica/genética , Mutação/genética , Cadeias Leves de Miosina/genética , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo
16.
J Food Prot ; 80(11): 1913-1923, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-29053422

RESUMO

The objective of this study was to develop and assess the efficacy of an aggressive deep cleaning sanitation standard operating procedure (DC-SSOP) in nine retail delicatessens to reduce persistent Listeria monocytogenes environmental contamination. The DC-SSOP was developed from combined daily SSOPs recommended by the Food Marketing Institute and input from experts in Listeria control from food manufacturing and sanitation. The DC-SSOP was executed by a trained professional cleaning service during a single 12-h shutdown period. A modified protocol from the U.S. Food and Drug Administration Bacteriological Analytical Manual was used to detect L. monocytogenes in samples from 28 food and nonfood contact surfaces that were collected immediately before and after each cleaning and in samples collected monthly for 3 months. The DC-SSOP significantly reduced L. monocytogenes prevalence overall during the 3-month follow-up period and produced variable results for persistent L. monocytogenes isolates. Six delis with historically low to moderate L. monocytogenes prevalence had no significant changes in the number of samples positive for L. monocytogenes after deep cleaning. Deep cleaning in very high prevalence delis (20 to 30% prevalence) reduced L. monocytogenes by 25.6% (Padj < 0.0001, n = 294) overall during the follow-up period. Among delis with extremely high prevalence (>30%), positive samples from nonfood contact surfaces were reduced by 19.6% (Padj = 0.0002, n = 294) during the follow-up period. The inability of deep cleaning to completely eliminate persistent L. monocytogenes was likely due to the diverse infrastructures in each deli, which may require more individualized intervention strategies.

17.
EuroIntervention ; 12(2): e250-6, 2016 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-27290684

RESUMO

AIMS: Pericardial effusion (PE) without obvious periprocedural complications (e.g., cardiac perforation, device erosion) may occur after transcatheter closure of secundum atrial septal defects (ASD). The aim of the study was to investigate the incidence and predictors of PE unrelated to procedural complications. METHODS AND RESULTS: We included all patients who had undergone successful percutaneous ASD closure from June 2009 to April 2014 (n=2,652) with no pre-existing PE or cardiac perforation or erosion. Transthoracic echocardiography (TTE) was performed during the procedure and one, three, and six months postoperatively. After device implantation, fifty patients (1.9%) developed new-onset PE (37 immediately, 13 during follow-up). These patients were asymptomatic, stable haemodynamically, and had no new arrhythmias. PE appeared mild (5.1±1.9 mm) and homogeneously echolucent by TTE. PE diminished spontaneously. Compared with 2,602 patients without PE, factors independently predicting asymptomatic PE were the device touching the atrial free wall, device size, patient age, and total defect size. Areas under the receiver operating characteristic curves were 0.78 (p<0.001), 0.66 (p<0.001) and 0.77 (p<0.001) for device size, patient age, and total defect size, respectively. CONCLUSIONS: This is the first systematic report of a new type of PE. Our data provide new insights into new-onset PE after percutaneous ASD closure.


Assuntos
Cateterismo Cardíaco , Comunicação Interatrial/cirurgia , Derrame Pericárdico/epidemiologia , Dispositivo para Oclusão Septal , Adolescente , Adulto , Idoso , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/cirurgia , Cateterismo Cardíaco/efeitos adversos , Criança , Ecocardiografia Transesofagiana/métodos , Feminino , Comunicação Interatrial/diagnóstico , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Derrame Pericárdico/diagnóstico , Dispositivo para Oclusão Septal/efeitos adversos , Resultado do Tratamento , Adulto Jovem
18.
J Thorac Cardiovasc Surg ; 152(2): 461-8, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27033027

RESUMO

OBJECTIVE: This study aims to report our preliminary experience and anatomic findings in the surgical treatment and postoperative management of hypertrophic obstructive cardiomyopathy. METHODS: This study included 277 patients with hypertrophic obstructive cardiomyopathy (168 [60.65%] were male), with a median age of 47 years (interquartile range, 35-54 years), who underwent surgical myectomy performed by 1 surgeon in Fuwai Hospital between May 2010 and April 2015. The median follow-up was 14 months (interquartile range, 7-24 months). RESULTS: A total of 127 patients (45.85%) underwent concomitant procedures, and 2 patients (0.72%) died in the early perioperative days. The left ventricular outflow gradient decreased from 78 mm Hg (interquartile range, 61-100 mm Hg) to 11 mm Hg (interquartile range, 8-15 mm Hg) when discharged (P < .001). Of the 228 patients with well-documented anatomic description, more than 80% had various intraventricular anomalies. The cumulative survival was 99.28% (95% confidence interval, 97.15-99.82) at 1 year and 96.98% (95% confidence interval, 92.56-98.79) at 5 years. Of the surviving 272 patients, 268 (98.53%) were categorized with functional class I and II of the New York Heart Association classification at the latest evaluation. CONCLUSIONS: Anomalous muscle bundles are common in hypertrophic obstructive cardiomyopathy, and they may lead to middle-apical obstruction. Surgical myectomy provides excellent clinical outcomes with low risk for sufficient relief of obstruction and radical correction of intraventricular anomalies in patients with hypertrophic obstructive cardiomyopathy.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Cardiomiopatia Hipertrófica/cirurgia , Defeitos dos Septos Cardíacos/cirurgia , Septos Cardíacos/cirurgia , Músculos Papilares/cirurgia , Obstrução do Fluxo Ventricular Externo/cirurgia , Adulto , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Cardiomiopatia Hipertrófica/mortalidade , Cardiomiopatia Hipertrófica/fisiopatologia , China , Feminino , Defeitos dos Septos Cardíacos/diagnóstico por imagem , Defeitos dos Septos Cardíacos/mortalidade , Defeitos dos Septos Cardíacos/fisiopatologia , Septos Cardíacos/diagnóstico por imagem , Septos Cardíacos/fisiopatologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Músculos Papilares/anormalidades , Músculos Papilares/diagnóstico por imagem , Músculos Papilares/fisiopatologia , Dados Preliminares , Recuperação de Função Fisiológica , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Obstrução do Fluxo Ventricular Externo/diagnóstico por imagem , Obstrução do Fluxo Ventricular Externo/mortalidade , Obstrução do Fluxo Ventricular Externo/fisiopatologia
19.
Ann Thorac Surg ; 102(1): 124-31, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27021034

RESUMO

BACKGROUND: Surgical extended septal myectomy is appropriate treatment for obstructive hypertrophic cardiomyopathy (HCM) with refractory symptoms. Using 3-layer speckle tracking imaging, we aimed to evaluate the effects of myectomy on left ventricular (LV) regions and the potential factors associated with LV reverse remodeling. METHODS: In 71 patients (mean age, 41.0 ± 15.0 years) undergoing septal myectomy, 3-layer speckle tracking was performed before myectomy and latest review. We evaluated the myectomy site (target anteroseptum) and LV free wall longitudinal strain (LS) and circumferential strain (CS) in endocardial, midmyocardial, and epicardial layers. The thickness of each free wall segment was calculated and totaled for the free wall thickness score. RESULTS: Compared with before myectomy, LS increased; however, CS decreased at the myectomy site after myectomy. For the free wall, LS and CS improved in all 3 layers after the procedure (all p < 0.05). Factors independently associated with latest-review free wall strain were free wall thickness score (LS, ß = -0.150; p < 0.001; CS, ß = -0.090; p < 0.001), age (LS, ß = 0.118; p < 0.001), and ΔLV outflow tract gradient (CS, ß = 0.039; p = 0.002). Factors independently associated with myectomy site strain were resected thickness (LS, ß = -0.439; p = 0.001; CS, ß = -0.736; p = 0.001), and age (LS, ß = 0.178; p < 0.001). CONCLUSIONS: Sufficient relief of obstruction and lower resected thickness in the target anteroseptum lead to more favorable remodeling. Free wall thickness score and age are important factors associated with reverse remodeling.


Assuntos
Cardiomiopatia Hipertrófica/cirurgia , Septos Cardíacos/cirurgia , Função Ventricular Esquerda/fisiologia , Remodelação Ventricular/fisiologia , Adulto , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/fisiopatologia , Ecocardiografia , Feminino , Seguimentos , Septos Cardíacos/diagnóstico por imagem , Humanos , Masculino , Período Pós-Operatório , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
Foodborne Pathog Dis ; 12(2): 151-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25569840

RESUMO

Based on recent risk assessments, up to 83% of listeriosis cases from deli meat in the United States are predicted to be from ready-to-eat deli meats contaminated during processing at retail grocery stores. Listeria monocytogenes is known to use sanitizer tolerance and biofilm formation to survive, but interplay of these mechanisms along with virulence potential and persistence mechanisms specific to deli environments had yet to be elucidated. In this study, 442 isolates from food and nonfood contact surfaces in 30 retail delis over 9 months were tested for inlA premature stop codons (PMSCs); inlA encodes InlA, which is necessary to cause listeriosis. A total of 96 isolates, composed of 23 persistent and 73 transient strains, were tested for adhesion and biofilm-forming ability and sanitizer tolerance. Only 10/442 isolates had inlA PMSCs (p<0.001). Strains with PMSCs were not persistent, even in delis with other persistent strains. Most (7/10) PMSC-containing isolates were collected from food contact surfaces (p<0.001); 6/10 PMSC-containing isolates were found in moderate prevalence delis (p<0.05). Persistent strains had enhanced adhesion on day 1 of a 5-day adhesion-biofilm formation assay. However, there was no significant difference in sanitizer tolerance between persistent and transient strains. Results suggest that foods contaminated with persistent L. monocytogenes strains from the retail environment are (1) likely to have wild-type virulence potential and (2) may persist due to increased adhesion and biofilm formation capacity rather than sanitizer tolerance, thus posing a significant public health risk.


Assuntos
Biofilmes/crescimento & desenvolvimento , Utensílios de Alimentação e Culinária , Listeria monocytogenes/fisiologia , Produtos da Carne/microbiologia , Carne/microbiologia , Restaurantes , Aderência Bacteriana , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/efeitos dos fármacos , Códon sem Sentido , Farmacorresistência Bacteriana , Doenças Transmitidas por Alimentos/epidemiologia , Doenças Transmitidas por Alimentos/microbiologia , Higienizadores de Mão/farmacologia , Humanos , Indiana/epidemiologia , Listeria monocytogenes/efeitos dos fármacos , Listeria monocytogenes/isolamento & purificação , Listeria monocytogenes/patogenicidade , Listeriose/epidemiologia , Listeriose/microbiologia , Listeriose/transmissão , Carne/economia , Produtos da Carne/economia , Testes de Sensibilidade Microbiana , Viabilidade Microbiana , Risco , Especificidade da Espécie , Virulência
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