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1.
Plant Physiol Biochem ; 200: 107804, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37269823

RESUMO

The tomato (Solanum lycopersicum) is widely consumed globally and renowned for its health benefits, including the reduction of cardiovascular disease and prostate cancer risk. However, tomato production faces significant challenges, particularly due to various biotic stresses such as fungi, bacteria, and viruses. To address this challenges, we employed the CRISPR/Cas9 system to modify the tomato NUCLEOREDOXIN (SlNRX) genes (SlNRX1 and SlNRX2) belonging to the nucleocytoplasmic THIOREDOXIN subfamily. CRISPR/Cas9-mediated mutations in SlNRX1 (slnrx1) plants exhibited resistance against bacterial leaf pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326, as well as the fungal pathogen Alternaria brassicicola. However, the slnrx2 plants did not display resistance. Notably, the slnrx1 demonstrated elevated levels of endogenous salicylic acid (SA) and reduced levels of jasmonic acid after Psm infection, in comparison to both wild-type (WT) and slnrx2 plants. Furthermore, transcriptional analysis revealed that genes involved in SA biosynthesis, such as ISOCHORISMATE SYNTHASE 1 (SlICS1) and ENHANCED DISEASE SUSCEPTIBILITY 5 (SlEDS5), were upregulated in slnrx1 compared to WT plants. In addition, a key regulator of systemic acquired resistance, PATHOGENESIS-RELATED 1 (PR1), exhibited increased expression in slnrx1 compared to WT. These findings suggest that SlNRX1 acts as a negative regulator of plant immunity, facilitating infection by the Psm pathogen through interference with the phytohormone SA signaling pathway. Thus, targeted mutagenesis of SlNRX1 is a promising genetic means to enhance biotic stress resistance in crop breeding.


Assuntos
Ácido Salicílico , Solanum lycopersicum , Ácido Salicílico/metabolismo , Solanum lycopersicum/genética , Melhoramento Vegetal , Pseudomonas syringae/fisiologia , Transdução de Sinais/genética , Ciclopentanos/metabolismo , Doenças das Plantas/microbiologia , Regulação da Expressão Gênica de Plantas
2.
RMD Open ; 9(1)2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36958767

RESUMO

OBJECTIVE: While many studies on the increased risk of cancer in patients with psoriasis are available, data on the risk of cancer in patients with psoriatic arthritis (PsA) are still scarce. We assessed the risk of cancer in patients with PsA in a nationwide population-based cohort in Korea. METHODS: From 2010 to June 2021, patients newly diagnosed with PsA and 1:10 age-matched and sex-matched controls were included in this study. The outcome was the incidence of overall and specific cancers. RESULTS: Total 162 cancers occurred in 4688 PsA patients (incidence rate 83.2 (95% CI 70.8 to 97.0) per 10 000 person-years) and 1307 cancers occurred in 46 880 controls (incidence rate 66.9 (95% CI 63.3 to 70.6) per 10 000 person-years). The adjusted HR (aHR) of overall cancer in PsA patients was 1.20 (95% CI 1.02 to 1.41). However, this significance disappeared when non-melanoma skin cancer (NMSC) was excluded (aHR 1.16, 95% CI 0.98 to 1.37). Among specific cancers, the risk of NMSC (aHR 3.64 (95% CI 1.61 to 8.23)), lymphoma (aHR 2.63 (95% CI 1.30 to 5.30)) and thyroid cancer (aHR 1.83 (95% CI 1.18 to 2.85)) was higher in patients with PsA than in controls. CONCLUSION: The risk of overall cancer was higher in patients with PsA than in the general population. Patients with PsA had increased risks of NMSC, lymphoma and thyroid cancer compared with the general population. Our findings suggest a need to conduct cancer screening by a detailed history and comprehensive clinical examination in patients with PsA.


Assuntos
Artrite Psoriásica , Linfoma , Neoplasias da Glândula Tireoide , Humanos , Artrite Psoriásica/complicações , Artrite Psoriásica/epidemiologia , Estudos de Coortes , Estudos Retrospectivos , República da Coreia/epidemiologia
3.
Joint Bone Spine ; 90(2): 105498, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36423779

RESUMO

OBJECTIVES: To investigate the incidence and risk of cerebro-cardiovascular comorbidities (stroke, acute myocardial infarction, venous thromboembolism, and pulmonary embolism) in anti-neutrophil cytoplasmic antibody-associated vasculitis using nationwide Korean population-based medical claims data. METHODS: We identified 1905 patients with newly diagnosed anti-neutrophil cytoplasmic antibody-associated vasculitis during 2009-2019. Incidence rates and hazard ratios with 95% confidence intervals were calculated to estimate the risk of cerebro-cardiovascular comorbidities in these patients and compared to age- and sex-matched controls (1:10) using the Cox proportional hazards model. RESULTS: Most patients had microscopic polyangiitis (42.5%), followed by granulomatosis with polyangiitis (29.1%) and eosinophilic granulomatosis with polyangiitis (28.4%). The annual incidence rate of anti-neutrophil cytoplasmic antibody-associated vasculitis in 2019 was 0.55 per 100,000 person-years. Cerebro-cardiovascular comorbidities occurred in 12.6%. Stroke was most common (64.6%), followed by venous thromboembolism (34.6%), pulmonary embolism (18.3%), and acute myocardial infarction (5.4%). Korean patients with anti-neutrophil cytoplasmic antibody-associated vasculitis were at a significantly (2.3 times) higher overall risk for cerebro-cardiovascular comorbidities than the general population (adjusted hazard ratios, 4.5, 3.1, and 2.0 times higher for pulmonary embolism, venous thromboembolism, and stroke, respectively). These findings were similar for patients with each subtype of anti-neutrophil cytoplasmic antibody-associated vasculitis. CONCLUSIONS: This is the first nationwide population-based study to demonstrate a significant risk of cerebro-cardiovascular comorbidities as complications of anti-neutrophil cytoplasmic antibody-associated vasculitis in Korean patients. Knowing these risks may enable personalized patient care and improve overall survival.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Infarto do Miocárdio , Embolia Pulmonar , Acidente Vascular Cerebral , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/epidemiologia , Anticorpos Anticitoplasma de Neutrófilos , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Embolia Pulmonar/epidemiologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Infarto do Miocárdio/epidemiologia
4.
Trials ; 23(1): 776, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104714

RESUMO

BACKGROUND: Cardiac evaluation using transthoracic echocardiography before noncardiac surgery is common in real-world practice. However, evidence supporting preoperative echocardiography is lacking. This study aims to evaluate the additional benefit of preoperative echocardiography in predicting postoperative cardiovascular events (CVE) in noncardiac surgery. METHODS: This study is designed as a multicenter, prospective study to assess the utility of preoperative echocardiography in patients undergoing intermediate- or high-risk noncardiac surgery. This trial comprises two studies: (1) a randomized controlled trial (RCT) for patients undergoing intermediate-risk surgery with fewer than three clinical risk factors from the revised cardiac risk index (intermediate-risk group) and (2) a prospective cohort study for patients undergoing intermediate-risk surgery with three or more clinical risk factors, or who undergo high-risk surgery regardless of the number of clinical risk factors (high-risk group). We hypothesize that the use of preoperative echocardiography will reduce postoperative CVEs in patients undergoing intermediate- to high-risk surgery through discovery of and further intervention for unexpected cardiac abnormalities before elective surgery. A total of 2330 and 2184 patients will be enrolled in the two studies. The primary endpoint is a composite of all-cause death; aborted sudden cardiac arrest; type I acute myocardial infarction; clinically diagnosed unstable angina; stress-induced cardiomyopathy; lethal arrhythmia, such as sustained ventricular tachycardia or ventricular fibrillation; and/or newly diagnosed or acutely decompensated heart failure within 30 days after surgery. DISCUSSION: This study will be the first large-scale prospective study examining the benefit of preoperative echocardiography in predicting postoperative CVE. The PREOP-ECHO trial will help doctors identify patients at risk of postoperative CVE using echocardiography and thereby reduce postoperative CVEs. TRIAL REGISTRATION: The Clinical Research Information Service KCT0006279 for RCT and KCT0006280 for prospective cohort study. Registered on June 21, 2021.


Assuntos
Infarto do Miocárdio , Projetos de Pesquisa , Estudos de Coortes , Humanos , Estudos Multicêntricos como Assunto , Infarto do Miocárdio/etiologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco
5.
Metabolomics ; 18(7): 48, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35781849

RESUMO

INTRODUCTION: Rheumatoid arthritis (RA) and osteoarthritis (OA) are clinicopathologically different. OBJECTIVES: We aimed to assess the feasibility of metabolomics in differentiating the metabolite profiles of synovial fluid between RA and OA using gas chromatography/time-of-flight mass spectrometry. METHODS: We first compared the global metabolomic changes in the synovial fluid of 19 patients with RA and OA. Partial least squares-discriminant, hierarchical clustering, and univariate analyses were performed to distinguish metabolites of RA and OA. These findings were then validated using synovial fluid samples from another set of 15 patients with RA and OA. RESULTS: We identified 121 metabolites in the synovial fluid of the first 19 samples. The score plot of PLS-DA showed a clear separation between RA and OA. Twenty-eight crucial metabolites, including hypoxanthine, xanthine, adenosine, citrulline, histidine, and tryptophan, were identified to be capable of distinguishing RA metabolism from that of OA; these were found to be associated with purine and amino acid metabolism. CONCLUSION: Our results demonstrated that metabolite profiling of synovial fluid could clearly discriminate between RA and OA, suggesting that metabolomics may be a feasible tool to assist in the diagnosis and advance the comprehension of pathological processes for diseases.


Assuntos
Artrite Reumatoide , Osteoartrite , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Metabolômica/métodos , Osteoartrite/metabolismo , Líquido Sinovial/metabolismo
6.
Eur J Radiol Open ; 9: 100419, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35445144

RESUMO

Connective tissue diseases (CTDs) demonstrating features of interstitial lung disease (ILD) include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), dermatomyositis (DM) and polymyositis (PM), ankylosing spondylitis (AS), Sjogren syndrome (SS), and mixed connective tissue disease (MCTD). On histopathology of lung biopsy in CTD-related ILDs (CTD-ILDs), multi-compartment involvement is an important clue, and when present, should bring CTD to the top of the list of etiologic differential diagnoses. Diverse histologic patterns including nonspecific interstitial pneumonia (NSIP), usual interstitial pneumonia (UIP), organizing pneumonia, apical fibrosis, diffuse alveolar damage, and lymphoid interstitial pneumonia can be seen on histology in patients with CTD-ILDs. Although proportions of ILDs vary, the NSIP pattern accounts for a large proportion, especially in SSc, DM and/or PM and MCTD, followed by the UIP pattern. In RA patients, interstitial lung abnormality (ILA) is reported to occur in approximately 20-60% of individuals of which 35-45% will have progression of the CT abnormality. Subpleural distribution and greater baseline ILA involvement are risk factors associated with disease progression. Asymptomatic CTD-ILDs or ILA patients with normal lung function and without evidence of disease progression can be followed without treatment. Immunosuppressive or antifibrotic agents for symptomatic and/or fibrosing CTD-ILDs can be used in patients who require treatment.

7.
ACS Appl Mater Interfaces ; 14(14): 16100-16107, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35377593

RESUMO

N-Acetylneuraminic acid (Neu5Ac), one of the abundant types of sialic acid, is an emerging anticancer agent owing to its ability to target selectins in the plasma membrane of cancer cells. Considering the functionality of Neu5Ac, obtaining novel Neu5Ac-conjugated materials with a selective and an enhanced antitumor activity has remained a challenge. Herein, we report the supramolecular materials of three novel amphiphiles composed of Neu5Ac as a hydrophilic segment and pyrene or adamantane as a hydrophobic segment. The synthetic amphiphiles 1, 2, and 3 self-assembled into ribbons, vesicles, and irregular aggregates in an aqueous solution, respectively. Among the materials, vesicles of amphiphile 2 showed the most substantial selectivity toward cancer cells, followed by cell death due to the production of reactive oxygen species by the pyrene group. The dual advantage of Neu5Ac-selectivity and the pyrene-cytotoxicity of vesicles of amphiphile 2 can provide a strategy for effective anticancer materials.


Assuntos
Ácido N-Acetilneuramínico , Membrana Celular/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Ácido N-Acetilneuramínico/metabolismo
8.
Acta Biomater ; 135: 520-533, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34454081

RESUMO

Myocardial ischemia-reperfusion (IR) generates stress-induced senescent cells (SISCs) that play an important role in the pathophysiology of adverse cardiac remodeling and heart failure via secretion of pro-inflammatory molecules and matrix-degrading proteases. Thus, removal of senescent cells using a senolytic drug could be a potentially effective treatment. However, clinical studies on cancer treatment with a senolytic drug have revealed that systemic administration of a senolytic drug often causes systemic toxicity. Herein we show for the first time that local delivery of a senolytic drug can effectively treat myocardial IR injury. We found that biodegradable poly(lactic-co-glycolic acid) nanoparticle-based local delivery of a senolytic drug (ABT263-PLGA) successfully eliminated SISCs in the IR-injured rat hearts without systemic toxicity. Consequently, the treatment ameliorated inflammatory responses and attenuated adverse remodeling. Surprisingly, the ABT263-PLGA treatment restored the cardiac function over time, whereas the cardiac function decreased over time in the no treatment group. Mechanistically, the ABT263-PLGA treatment not only markedly reduced the expression of pro-inflammatory molecules and matrix-degrading proteases, but also induced macrophage polarization from the inflammatory phase to the reparative phase via efferocytosis of apoptotic SISCs by macrophages. Therefore, the senolytic strategy with ABT263-PLGA in the early stage of myocardial IR injury may be an effective therapeutic option for myocardial infarction. STATEMENT OF SIGNIFICANCE: This study describes a local injection of senolytic drug-loaded nanoparticles that selectively kills stress-induced senescent cells (SISCs) in infarcted heart. Removal of SISCs decreases inflammatory cytokines and normal cell death. We firstly revealed that further efferocytosis of apoptotic senescent cells by macrophages restores cardiac function after myocardial ischemia-reperfusion injury. Importantly, a local injection of senolytic drug did not exhibit systemic toxicity, but a systemic injection did. Our findings not only spotlight the basic understanding of therapeutic potential of senolysis in infarcted myocardium, but also pave the way for the further application of senolytic drug for non-aging related diseases.


Assuntos
Infarto do Miocárdio , Traumatismo por Reperfusão Miocárdica , Animais , Portadores de Fármacos/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Miocárdio , Ratos , Reperfusão , Remodelação Ventricular
9.
J Cardiol Cases ; 23(5): 193-197, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33995694

RESUMO

Knowledge of the multi-organ involvement in hypereosinophilic syndrome (HES) is important for the diagnosis and care of patients with this condition, even in cases with atypical presentation. This report aims to describe cerebral embolic infarction and intracardiac atypical linear-shaped thrombus in a patient with idiopathic HES and to discuss the approach of appropriate diagnosis and timely interventional management. A 55-year-old man presented with general weakness, including left-sided weakness, mild cognitive dysfunction, and mild exertional dyspnea for about 2 weeks. Initial magnetic resonance imaging for evaluating the brain showed multifocal acute to subacute infarction of both cerebral hemispheres and both cerebellums. Laboratory findings revealed leukocytosis (25,620 cells/mm3) and eosinophilia (54.9%). To evaluate the intracardiac embolic source, the patient underwent echocardiography, and a 1.5 cm linear thread-like and mobile mass was detected. Consequently, the patient was diagnosed with idiopathic HES. After bone marrow biopsy, corticosteroid and hydroxyurea were administered to control the eosinophilia. This case indicates that HES can present as a floating intracardiac atypical linear-shaped thrombus attached to the left ventricle. After appropriate diagnostic approaches, proper treatment could be given for the patient. .

10.
PLoS One ; 16(1): e0231994, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33497388

RESUMO

Exosomes are a type of extracellular vesicles containing mRNA, miRNA, and proteins of origin cells, which can control the characteristics of other cells or surroundings. Despite increasing evidence on oncogenic properties of tumor-derived exosomes, fibrosarcoma-derived exosomes remain largely unrevealed. While the proper extraction and characterization of exosomes is critical in exosomes research, there are various limitations in techniques to measure the size and homogeneity of exosomes. Here, we analyzed exosomes from a fibrosarcoma cell line WEHI-164 compared with a breast cancer cell line MDA-MD-231 as a control. Results from dot blot and western blot analysis demonstrated that GM1 ganglioside, and TSG101, HSC70 and GAPDH proteins were contained in exosomes from the WEHI-164 fibrosarcoma cell line. The existence of tetraspanins such as CD81, CD63 and CD9 was confirmed in the exosomes by ExoView analysis. The results obtained from TEM showed their sphere-like shapes of around 50 to 70 nm in radius. Through DLS, we found out that the mean radius of the exosomes derived from WEHI-164 and MDA-MB-231 cell lines was 94.4 nm and 107.8 nm, respectively, with high homogeneity. When comparing the radius measured by TEM with the radius measured by DLS, it was revealed that the difference between the two methods was about 40 nm. This study has significance in characterizing the molecular properties of exosomes from a fibrosarcoma, which has not been researched much before, and in providing clear evidence that DLS can be used as an efficient, convenient and noninvasive technique to simply check the homogeneity and size of exosomes.


Assuntos
Exossomos/metabolismo , Fibrossarcoma/metabolismo , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/metabolismo , Difusão Dinâmica da Luz , Complexos Endossomais de Distribuição Requeridos para Transporte/metabolismo , Vesículas Extracelulares/metabolismo , Feminino , Proteínas de Choque Térmico HSC70/metabolismo , Humanos , Integrina beta1/metabolismo , Tetraspanina 28/metabolismo , Tetraspanina 30/metabolismo , Fatores de Transcrição/metabolismo
11.
J Cardiol Cases ; 22(4): 192-194, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33014203

RESUMO

A 24-year-old male patient presented with symptoms of acute progressive dyspnea and chest pain. Transthoracic echocardiography demonstrated a mobile mass-like lesion attached to the tricuspid valve, as well as a holodiastolic flow reversal in the descending and abdominal aorta, as increased retrograde flow. We also evaluated the vegetation-like lesion by transesophageal echocardiography. As a result, we were able to diagnose the rupture of the sinus of Valsalva with shunt flow between the aorta and the right heart that had manifested as sudden chest pain and acute dyspnea. The patient underwent surgical repair for this ruptured lesion. After surgery, there was no evidence of residual shunt flow. The objective of this report is to describe a rare presentation of a ruptured sinus of Valsalva and to discuss the importance of adequate diagnosis using advanced imaging modalities. .

12.
J Biol Chem ; 295(52): 18284-18300, 2020 12 25.
Artigo em Inglês | MEDLINE | ID: mdl-33109611

RESUMO

Oxygen regulates hypoxia-inducible factor (HIF) transcription factors to control cell metabolism, erythrogenesis, and angiogenesis. Whereas much has been elucidated about how oxygen regulates HIF, whether lipids affect HIF activity is un-known. Here, using cultured cells and two animal models, we demonstrate that lipoprotein-derived fatty acids are an independent regulator of HIF. Decreasing extracellular lipid supply inhibited HIF prolyl hydroxylation, leading to accumulation of the HIFα subunit of these heterodimeric transcription factors comparable with hypoxia with activation of downstream target genes. The addition of fatty acids to culture medium suppressed this signal, which required an intact mitochondrial respiratory chain. Mechanistically, fatty acids and oxygen are distinct signals integrated to control HIF activity. Finally, we observed lipid signaling to HIF and changes in target gene expression in developing zebrafish and adult mice, and this pathway operates in cancer cells from a range of tissues. This study identifies fatty acids as a physiological modulator of HIF, defining a mechanism for lipoprotein regulation that functions in parallel to oxygen.


Assuntos
Ácidos Graxos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Lipoproteínas/química , Oxigênio/metabolismo , Animais , Perfilação da Expressão Gênica , Humanos , Hidroxilação , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Lipoproteínas/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais , Peixe-Zebra
13.
J Cardiol Cases ; 22(1): 5-10, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32636960

RESUMO

A 55-year-old woman presented with a history of constitutional symptoms with exertional dyspnea, orthopnea, and cough for one month. She developed progressive heart failure symptoms. Initial computed tomography revealed a large left atrial mass with compression of pulmonary veins and mitral valve. Surgical resection was performed, and histologic examination revealed an intimal sarcoma. The most effective treatment has been found to be a surgical resection, with chemotherapy and radiotherapy. The objective of this report is to describe a common presentation of a rare disease, and to discuss the significance of appropriate diagnosis, pathological findings, and timely interventional management. .

14.
Am J Case Rep ; 21: e923299, 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32565535

RESUMO

BACKGROUND Thyroid function is closely related to the cardiovascular system. Pericardial effusion is a well-known complication of hypothyroidism. It is common for massive pericardial effusion to progress to tamponed heart with hypotension, but not high blood pressure. CASE REPORT A 46-year-old woman presented to the hospital with dysarthria and left-side weakness of the upper limb which had started 30 minutes before her arrival at the hospital. The patient showed hypertensive emergency (213/124 mmHg) with intracerebral hemorrhage. Further evaluation for high blood pressure and transthoracic echocardiography demonstrated the presence of a large amount of pericardial effusion, and urgent pericardiocentesis was performed. The laboratory examination showed elevated thyroid-stimulating hormone and decreased free thyroxine level, leading to a diagnosis of primary hypothyroidism. The administration of current medications was maintained, including thyroid hormone replacement and anti-hypertensive drugs. CONCLUSIONS A rare case of profound hypothyroidism presenting with hypertensive crisis and massive pericardial effusion is described in this report.


Assuntos
Hipertensão Maligna/diagnóstico , Hipotireoidismo/diagnóstico por imagem , Derrame Pericárdico/diagnóstico por imagem , Feminino , Terapia de Reposição Hormonal , Humanos , Hipertensão Maligna/terapia , Hipotireoidismo/complicações , Hipotireoidismo/tratamento farmacológico , Pessoa de Meia-Idade , Derrame Pericárdico/terapia , Pericardiocentese , Tiroxina/uso terapêutico
15.
Sci Adv ; 6(18): eaaz0952, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32494669

RESUMO

Because of poor engraftment and safety concerns regarding mesenchymal stem cell (MSC) therapy, MSC-derived exosomes have emerged as an alternative cell-free therapy for myocardial infarction (MI). However, the diffusion of exosomes out of the infarcted heart following injection and the low productivity limit the potential of clinical applications. Here, we developed exosome-mimetic extracellular nanovesicles (NVs) derived from iron oxide nanoparticles (IONPs)-incorporated MSCs (IONP-MSCs). The retention of injected IONP-MSC-derived NVs (IONP-NVs) within the infarcted heart was markedly augmented by magnetic guidance. Furthermore, IONPs significantly increased the levels of therapeutic molecules in IONP-MSCs and IONP-NVs, which can reduce the concern of low exosome productivity. The injection of IONP-NVs into the infarcted heart and magnetic guidance induced an early shift from the inflammation phase to the reparative phase, reduced apoptosis and fibrosis, and enhanced angiogenesis and cardiac function recovery. This approach can enhance the therapeutic potency of an MSC-derived NV therapy.


Assuntos
Exossomos , Células-Tronco Mesenquimais , Infarto do Miocárdio/terapia , Apoptose , Exossomos/metabolismo , Humanos , Nanopartículas Magnéticas de Óxido de Ferro
16.
Heart Surg Forum ; 23(3): E370-E375, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32524986

RESUMO

BACKGROUND: The progress of mild ischemic mitral regurgitation (MR) after isolated coronary artery bypass is not clear. We aimed to determine the proportion of patients with mild ischemic MR undergoing isolated coronary artery bypass grafting (CABG) presenting with regression of or persistent MR one year after CABG and to identify the significantly different echocardiographic variables between regressing and persistent MR. METHODS: Sixty-three patients with preoperative mild ischemic MR were categorized into an MR- regression or an MR-persistence group one year after isolated CABG. The echocardiographic indices, indicating mitral leaflet configuration and remodeling of the left ventricle (LV), were measured before and one year after the surgery. RESULTS: One year after CABG, MR regressed in 60% (38/63) and persisted in 40% (25/63) of the patients. The left ventricular diameter, volume, and sphericity and anteroposterior diameter of the mitral annulus improved only in the MR-regression group, while the ejection fraction improved in both groups (47.7% ± 12.4% from 40.1% ± 11.3%, P < .001 in the regression group and 43.2% ± 14.0% from 39.3% ± 11.6%, P = .035 in the persistence group). A >15% decrease in the LV end-systolic volume was noted more frequently in the MR-regression group (60.5% versus 30%, P = .027). The leaflet angle did not show asymmetry or significant changes in both groups. CONCLUSIONS: Isolated CABG improved mild MR in most patients with mild ischemic MR. These patients showed greater reverse remodeling after revascularization than the patients with persistent MR after isolated CABG. Additional tests, which can predict LV reverse remodeling, are needed to predict persistent MR.


Assuntos
Insuficiência da Valva Mitral/etiologia , Isquemia Miocárdica/complicações , Revascularização Miocárdica/métodos , Idoso , Angiografia Coronária , Ecocardiografia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico , Insuficiência da Valva Mitral/prevenção & controle , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/cirurgia , Estudos Retrospectivos , Índice de Gravidade de Doença
17.
Sci Adv ; 6(13): eaay6994, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32284967

RESUMO

The clinical use of human bone marrow-derived mesenchymal stem cells (BM-MSCs) has been hampered by their poor performance after transplantation into failing hearts. Here, to improve the therapeutic potential of BM-MSCs, we developed a strategy termed in vivo priming in which BM-MSCs are primed in vivo in myocardial infarction (MI)-induced hearts through genetically engineered hepatocyte growth factor-expressing MSCs (HGF-eMSCs) that are encapsulated within an epicardially implanted 3D cardiac patch. Primed BM-MSCs through HGF-eMSCs exhibited improved vasculogenic potential and cell viability, which ultimately enhanced vascular regeneration and restored cardiac function to the MI hearts. Histological analyses further demonstrated that the primed BM-MSCs survived longer within a cardiac patch and conferred cardioprotection evidenced by substantially higher numbers of viable cardiomyocytes in the MI hearts. These results provide compelling evidence that this in vivo priming strategy can be an effective means to enhance the cardiac repair of MI hearts.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos , Cardiopatias/terapia , Fator de Crescimento de Hepatócito/genética , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Animais , Técnicas de Cultura de Células , Terapia Baseada em Transplante de Células e Tecidos/métodos , Modelos Animais de Doenças , Expressão Gênica , Engenharia Genética , Cardiopatias/etiologia , Fator de Crescimento de Hepatócito/metabolismo , Fator de Crescimento de Hepatócito/farmacologia , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/etiologia , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/terapia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Suínos
18.
Clin Exp Rheumatol ; 38 Suppl 126(4): 40-46, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31969226

RESUMO

OBJECTIVES: The aim of this study was to evaluate the incidence and risk of non-Hodgkin's lymphoma (NHL) and thyroid cancer in patients with primary Sjögren's syndrome (pSS) using the Korean National Health Insurance Service (NHIS) claims database. METHODS: pSS was identified using the Korean NHIS medical claims database between 2007 and 2017. The case definition required more than one visit based on the SS diagnostic code and the registration system for rare and incurable diseases. We included all admissions with a primary diagnosis of lymphoma and thyroid cancer. RESULTS: The pSS incidence was 1.88 cases/100,000 inhabitants. Female patients had a higher incidence than male patients, with a female-to-male ratio of 7.65:1. Of those, we identified 18 (0.34%), 1 (0.02%) and 29 (0.56%) patients with NHL, Hodgkin's disease and thyroid cancer, respectively. For pSS, the standardised incidence ratios for NHL and thyroid cancer were 6.32 (95% confidence interval [CI] 4.09-9.38) and 1.23 (95% CI 0.88-1.68), respectively. Compared with the general population, female patients with pSS had a 6.95-fold higher risk of developing NHL, while the male patients did not. Patients with pSS did not have a higher risk of developing thyroid cancer. CONCLUSIONS: Although pSS is associated with a higher risk of developing NHL, the risk of NHL appears to have decreased compared with that in previous studies. Our study suggests that the risk of NHL or thyroid cancer with SS is not higher than that reported in previous studies.


Assuntos
Linfoma não Hodgkin , Síndrome de Sjogren , Neoplasias da Glândula Tireoide , Feminino , Humanos , Seguro Saúde , Linfoma não Hodgkin/diagnóstico , Linfoma não Hodgkin/epidemiologia , Masculino , República da Coreia/epidemiologia , Fatores de Risco , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia
19.
J Bone Miner Metab ; 37(1): 142-151, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29372335

RESUMO

Bone health has been associated with oxidative stress and antioxidants have received interest to this end. Serum uric acid (SUA), an end product of purine metabolism in humans, has recently shown antioxidant properties regarding bone health, but there are conflicting results. The aim of this study was to investigate the relationship between SUA levels and lumbar spine bone mineral density (BMD) in clinically apparently healthy males aged 40-60 years. We performed a cross-sectional study of 6588 Korean males who completed a health-screening program from January 2011 to December 2014. Of the study participants, the mean age was 48.2 ± 10.7 years. Multiple regression analyses resulted in a significant positive association with lumbar spine BMD across SUA quintiles in a dose-response manner after adjusting for various confounding factors (p = 0.013); for each 1 mg/dl increase of SUA, BMD rose by 0.0054 g/cm2 (p = 0.004). Stratified analyses revealed that this association between SUA and lumbar spine BMD was consistently observed across all clinically relevant subgroups. The present study demonstrated a positive association in males between SUA and lumbar spine BMD, suggesting that SUA could have a profitable effect on bone metabolism.


Assuntos
Densidade Óssea/fisiologia , Vértebras Lombares/fisiologia , Programas de Rastreamento , Ácido Úrico/sangue , Alcoolismo/sangue , Ácido Ascórbico/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Cálcio/metabolismo , Estudos Transversais , Dieta , Exercício Físico , Taxa de Filtração Glomerular , Humanos , Resistência à Insulina , Masculino , Pessoa de Meia-Idade , Fumar/efeitos adversos
20.
Korean J Intern Med ; 33(1): 102-112, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28602063

RESUMO

BACKGROUND/AIMS: The aim of our study was to compare the characteristics of nosocomial infective endocarditis (NIE) with community-acquired infective endocarditis (CIE) and to determine independent risk factors for in-hospital death. METHODS: We retrospectively reviewed the medical records of 560 patients diagnosed with infective endocarditis. NIE was defined by a diagnosis made > 72 hours after hospital admission or within 2 months of hospital discharge. RESULTS: Among the 560 cases reviewed, 121 were classified as NIE. Compared with patients with CIE, patients with NIE were older (mean ± SD, 51.30±18.01 vs. 59.76±14.87, p < 0.001). The in-hospital death rate of the NIE group was much higher than that of the CIE group (27.3% vs. 5.9%, p < 0.001). More patients with NIE had central intravenous catheters, and were undergoing hemodialysis (p < 0.001). Methicillin-resistant Staphylococcus aureus (MRSA) was the most common causal microorganism of NIE, and MRSA (p < 0.001) and fungus (p = 0.002) were more common in NIE compared with CIE. On multiple analysis, age, liver cirrhosis, cancer chemotherapy, central intravenous catheter, hemodialysis, and genitourinary tract manipulation were independent clinical risk factors for NIE. Among the patients with NIE, 33 died during their hospital admission. The independent risk factors for in-hospital death were older age (adjusted odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.07; p = 0.037) and chemotherapy for malignancy (adjusted OR, 3.89; 95% CI, 1.18 to 12.87; p = 0.026). CONCLUSIONS: Because of the considerable incidence of NIE and its poor prognosis, we should pay attention to early diagnosis and active management of NIE, especially for older patients and patients receiving chemotherapy.


Assuntos
Infecção Hospitalar/mortalidade , Endocardite Bacteriana/mortalidade , Adulto , Fatores Etários , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/mortalidade , Infecção Hospitalar/microbiologia , Endocardite Bacteriana/microbiologia , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina , Prognóstico , República da Coreia/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/mortalidade
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