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1.
J Am Chem Soc ; 143(37): 15073-15083, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34520194

RESUMO

Proteolysis targeting chimeras (PROTACs) represent a new class of promising therapeutic modalities. PROTACs hijack E3 ligases and the ubiquitin-proteasome system (UPS), leading to selective degradation of the target proteins. However, only a very limited number of E3 ligases have been leveraged to generate effective PROTACs. Herein, we report that the KEAP1 E3 ligase can be harnessed for targeted protein degradation utilizing a highly selective, noncovalent small-molecule KEAP1 binder. We generated a proof-of-concept PROTAC, MS83, by linking the KEAP1 ligand to a BRD4/3/2 binder. MS83 effectively reduces protein levels of BRD4 and BRD3, but not BRD2, in cells in a concentration-, time-, KEAP1- and UPS-dependent manner. Interestingly, MS83 degrades BRD4/3 more durably than the CRBN-recruiting PROTAC dBET1 in MDA-MB-468 cells and selectively degrades BRD4 short isoform over long isoform in MDA-MB-231 cells. It also displays improved antiproliferative activity than dBET1. Overall, our study expands the limited toolbox for targeted protein degradation.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34469300

RESUMO

Rain streaks and raindrops are two natural phenomena, which degrade image capture in different ways. Currently, most existing deep deraining networks take them as two distinct problems and individually address one, and thus cannot deal adequately with both simultaneously. To address this, we propose a Dual Attention-in-Attention Model (DAiAM) which includes two DAMs for removing both rain streaks and raindrops. Inside the DAM, there are two attentive maps - each of which attends to the heavy and light rainy regions, respectively, to guide the deraining process differently for applicable regions. In addition, to further refine the result, a Differential-driven Dual Attention-in-Attention Model (D-DAiAM) is proposed with a "heavy-to-light" scheme to remove rain via addressing the unsatisfying deraining regions. Extensive experiments on one public raindrop dataset, one public rain streak and our synthesized joint rain streak and raindrop (JRSRD) dataset have demonstrated that the proposed method not only is capable of removing rain streaks and raindrops simultaneously, but also achieves the state-of-the-art performance on both tasks.

4.
Cell Chem Biol ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34469831

RESUMO

Nuclear receptor binding SET domain protein 3 (NSD3), a gene located within the 8p11-p12 amplicon frequently detected in human cancers, encodes a chromatin modulator and an attractive onco-target. However, agents that effectively suppress NSD3-mediated oncogenic actions are currently lacking. We report the NSD3-targeting proteolysis targeting chimera (PROTAC), MS9715, which achieves effective and specific targeting of NSD3 and associated cMyc node in tumor cells. MS9715 is designed by linking BI-9321, a NSD3 antagonist, which binds NSD3's PWWP1 domain, with an E3 ligase VHL ligand. Importantly, MS9715, but not BI-9321, effectively suppresses growth of NSD3-dependent hematological cancer cells. Transcriptomic profiling demonstrates that MS9715, but not BI-9321, effectively suppresses NSD3-and cMyc-associated gene expression programs, resembling effects of the CRISPR-Cas9-mediated knockout of NSD3. Collectively, these results suggest that pharmacological degradation of NSD3 as an attractive therapeutic strategy, which co-suppresses NSD3- and cMyc-related oncogenic nodes, is superior to blocking the PWWP1 domain of NSD3.

5.
Ecotoxicol Environ Saf ; 223: 112571, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34352584

RESUMO

The present study investigates whether paraquat (PQ) regulates polarization of alveolar macrophages through glycolysis and promotes the occurrence of acute lung injury in rats. In vivo, the PQ intraperitoneal injection was used to construct a model of acute lung injury in rats. In vitro, the study measured the effect of different concentrations of PQ on the viability of the alveolar macrophages, and explored the polarization and glycolysis metabolism of alveolar macrophages at different time points after PQ intervention. Compared with the normal control (NC) group, the lung pathological damage in rats increased gradually after PQ poisoning, reaching a significant degree at 48 h after poisoning. The PQ-poisoned rat serum showed increased expressions of interleukin-6 (IL-6), tumor necrosis factor- α (TNF-α), and M1 macrophage marker, iNOS, while the expression of interleukin-10 (IL-10) and M2 macrophage marker, Arg1, decreased. The toxic effect of PQ on alveolar macrophages was dose- and time-dependent. Compared with the NC group, IL-6 and TNF-α in the cell supernatant gradually increased after PQ intervention, while the IL-10 content gradually decreased. The PQ intervention in alveolar macrophages increased the expression of intracellular glycolysis rate-limiting enzyme pyruvate kinase isozymes M1/M2 (PKM1/M2), lactate, lactate/pyruvate ratio, and the polarization of alveolar macrophage towards M1. Inhibition of cellular glycolysis significantly reduced the PQ-induced alveolar macrophage polarization to M1 type. Thus, PQ induced increased polarization of lung macrophages toward M1 and decreased polarization toward M2, promoting acute lung injury. Therefore, it can be concluded that PQ regulates the polarization of alveolar macrophages through glycolysis.


Assuntos
Lesão Pulmonar Aguda , Paraquat , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Glicólise , Pulmão/metabolismo , Macrófagos Alveolares/metabolismo , Paraquat/toxicidade , Ratos , Fator de Necrose Tumoral alfa/metabolismo
6.
Molecules ; 26(15)2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34361594

RESUMO

Carbon is the crucial source of energy during aerobic composting. There are few studies that explore carbon preservation by inoculation with microbial agents during goat manure composting. Hence, this study inoculated three proportions of microbial agents to investigate the preservation of carbon during goat manure composting. The microbial inoculums were composed of Bacillus subtilis, Bacillus licheniformis, Trichoderma viride, Aspergillus niger, and yeast, and the proportions were B1 treatment (1:1:1:1:2), B2 treatment (2:2:1:1:2), and B3 treatment (3:3:1:1:2). The results showed that the contents of total organic carbon were enriched by 12.21%, 4.87%, and 1.90% in B1 treatment, B2 treatment, and B3 treatment, respectively. The total organic carbon contents of B1 treatment, B2 treatment, and B3 treatment were 402.00 ± 2.65, 366.33 ± 1.53, and 378.33 ± 2.08 g/kg, respectively. B1 treatment significantly increased the content of total organic carbon compared with the other two treatments (p < 0.05). Moreover, the ratio of 1:1:1:1:2 significantly reduced the moisture content, pH value, EC value, hemicellulose, and lignin contents (p < 0.05), and significantly increased the GI value and the content of humic acid carbon (p < 0.05). Consequently, the preservation of carbon might be a result not only of the enrichment of the humic acid carbon and the decomposition of hemicellulose and lignin, but also the increased OTU amount and Lactobacillus abundance. This result provided a ratio of microbial agents to preserve the carbon during goat manure aerobic composting.


Assuntos
Inoculantes Agrícolas/metabolismo , Carbono/metabolismo , Compostagem/métodos , Esterco/microbiologia , Animais , Cabras , Substâncias Húmicas
7.
Phytomedicine ; 91: 153671, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34425471

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of Hua Shi Bai Du Granule (Q-14) plus standard care compared with standard care alone in adults with coronavirus disease (COVID-19). STUDY DESIGN: A single-center, open-label, randomized controlled trial. SETTING: Wuhan Jinyintan Hospital, Wuhan, China, February 27 to March 27, 2020. PARTICIPANTS: A total of 204 patients with laboratory-confirmed COVID-19 were randomized into the treatment group and control group, consisting of 102 patients in each group. INTERVENTIONS: In the treatment group, Q-14 was administered at 10 g (granules) twice daily for 14 days, plus standard care. In the control group, patients were provided standard care alone for 14 days. MAIN OUTCOME MEASURE: The primary outcome was the conversion time for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral assay. Adverse events were analyzed in the safety population. RESULTS: Among the 204 patients, 195 were analyzed according to the intention-to-treat principle. A total of 149 patients (71 vs. 78 in the treatment and control groups, respectively) tested negative via the SARS-CoV-2 viral assay. There was no statistical significance in the conversion time between the treatment group and control group (Full analysis set: Median [interquartile range]: 10.00 [9.00-11.00] vs. 10.00 [9.00-11.00]; Mean rank: 67.92 vs. 81.44; P = 0.051). The recovery time for fever was shorter in the treatment group than in the control group. The disappearance rate of symptoms like cough, fatigue, and chest discomfort was significantly higher in the treatment group. In chest computed tomography (CT) examinations, the overall evaluation of chest CT examination after treatment compared with baseline showed that more patients improved in the treatment group. There were no significant differences in the other outcomes. CONCLUSION: The combination of Q-14 and standard care for COVID-19 was useful for the improvement of symptoms (such as fever, cough, fatigue, and chest discomfort), but did not result in a significantly higher probability of negative conversion in the SARS-CoV-2 viral assay. No serious adverse events were observed. TRIAL REGISTRATION: ChiCTR2000030288.


Assuntos
COVID-19 , Medicamentos de Ervas Chinesas/uso terapêutico , COVID-19/terapia , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
8.
J Cardiovasc Pharmacol ; 78(1): e30-e39, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-34232224

RESUMO

ABSTRACT: Mitophagy is involved in the development of various cardiovascular diseases, such as atherosclerosis, heart failure, myocardial ischemia/reperfusion injury, and hypertension. Mitophagy is essential for maintaining intracellular homeostasis and physiological function in most cardiovascular origin cells, such as cardiomyocytes, endothelial cells, and vascular smooth muscle cells. Mitophagy is crucial to ensuring energy supply by selectively removing dysfunctional mitochondria, maintaining a balance in the number of mitochondria in cells, ensuring the integrity of mitochondrial structure and function, maintaining homeostasis, and promoting cell survival. Substantial research has indicated a "dual" effect of mitophagy on cardiac function, with inadequate and increased mitochondrial degradation both likely to influence the progression of cardiovascular disease. This review summarizes the main regulatory pathways of mitophagy and emphasizes that an appropriate amount of mitophagy can prevent endothelial cell injury, vascular smooth muscle cell proliferation, macrophage polarization, and cardiomyocyte apoptosis, avoiding further progression of cardiovascular diseases.

9.
J Neurosci Methods ; 358: 109181, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33836172

RESUMO

BACKGROUND: Recent progress in optically pumped magnetometers (OPMs) and high-temperature superconducting quantum interference devices (SQUIDs) has facilitated the development of an on-scalp magnetoencephalography (MEG) system that offers high signal intensity and flexibility at a lower cost. While the on-scalp sensor array has high flexibility, it brings new challenges to accurate sensor-to-brain coregistration, which is essential for MEG source localization. NEW METHOD: A novel automatic filtering algorithm based on plane segmentation was proposed to locate on-scalp MEG sensors in 3D images reconstructed from optical scanning. Global image registration was employed for the automatic alignment of anatomical images and sensor positions. RESULTS: Seventy-one sensor dummies on the scalp were located and registered to brain anatomical images. The deviations of the sensor location and orientation from the averaged result of 10 measurements were less than 1 mm and 0.6°, respectively. The entire process could be completed in less than 4 min. COMPARISON WITH EXISTING METHODS: Compared with existing methods that involve various manual procedures, such as moving digitizers to fiducials and repeatedly pulling out sensors, our proposed coregistration method is more efficient and accurate. CONCLUSION: An automatic method for the coregistration of anatomical structure and on-scalp sensors that will have a large impact on the practical use of on-scalp MEG is developed.


Assuntos
Magnetoencefalografia , Couro Cabeludo , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Imageamento por Ressonância Magnética
11.
Oxid Med Cell Longev ; 2021: 8836818, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33488945

RESUMO

Sigma-1 receptor (Sig1R), a chaperone in the endoplasmic reticulum (ER) membrane, has been implicated in cardiac hypertrophy; however, its role in cardiac fibroblast activation has not been established. This study investigated the possible association between Sig1R and this activation by subjecting mice to sham, transverse aortic constriction (TAC), and TAC plus fluvoxamine (an agonist of Sig1R) treatments. Cardiac function and fibrosis were evaluated four weeks later by echocardiography and histological staining. In an in vitro study, neonatal rat cardiac fibroblasts were treated with fluvoxamine or NE-100 (an antagonist of Sig1R) in the presence or absence of transforming growth factor beta1 (TGF-ß1). Fibrotic markers, ER stress pathways, and autophagy were then investigated by qPCR, western blotting, immunofluorescence, confocal microscopy, and transmission electron microscopy. Fluvoxamine treatment reduced cardiac fibrosis, preserved cardiac function, and attenuated cardiac fibroblast activation. Inhibition of the IRE1/XBP1 pathway, a branch of ER stress, by a specific inhibitor of IRE1 endonuclease activity, attenuated the pathological process. Fluvoxamine stimulation of Sig1R restored autophagic flux in cardiac fibroblasts, indicating that Sig1R appears to play a protective role in the activation of cardiac fibroblasts by inhibiting the IRE1 pathway and restoring autophagic flux. Sig1R may therefore represent a therapeutic target for cardiac fibrosis.


Assuntos
Autofagia , Estresse do Retículo Endoplasmático , Fibrose/prevenção & controle , Cardiopatias/prevenção & controle , Proteínas de Membrana/antagonistas & inibidores , Substâncias Protetoras/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Receptores sigma/metabolismo , Animais , Fibrose/etiologia , Fibrose/metabolismo , Fibrose/patologia , Cardiopatias/etiologia , Cardiopatias/metabolismo , Cardiopatias/patologia , Masculino , Camundongos , Ratos , Receptores sigma/genética , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
12.
BMC Cardiovasc Disord ; 21(1): 9, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407150

RESUMO

BACKGROUND: Both systemic-pulmonary shunt and arterial duct stent could be the palliation of duct-dependent pulmonary circulation. We aimed to compare the safety and efficacy of the two approaches. METHODS: The PubMed, EMBASE, and Cochrane Library databases were searched through December 2019 for studies comparing stent implantation and surgical shunt in duct-dependent pulmonary circulation. The baseline characteristics included ventricle physiology and cardiac anomaly. The main outcomes were hospital stay and total mortality. Additional outcomes included procedural complications, intensive care unit (ICU) stay, pulmonary artery growth at follow-up, and other indexes. A random- or fixed-effects model was used to summarize the estimates of the mean difference (MD)/risk ratio (RR) with 95% confidence intervals (CIs). RESULTS: In total, 757 patients with duct-dependent pulmonary circulation from six studies were included. Pooled estimates of hospital stay (MD, - 4.83; 95% CI - 7.92 to - 1.74; p < 0.05), total mortality (RR 0.44; 95% CI 0.28-0.70; p < 0.05), complications (RR 0.49; 95% CI 0.30-0.81; p < 0.05) and ICU stay (MD, - 4.00; 95% CI - 5.96 to - 2.04; p < 0.05) favored the stent group. Significant differences were found in the proportions of patients with a single ventricle (RR 0.82; 95% CI 0.68-0.98; p < 0.05) or a double ventricle (RR 1.23; 95% CI 1.07-1.41; p < 0.05) between the stent and shunt groups. Additionally, pulmonary artery growth showed no significant differences between the two groups. CONCLUSION: Arterial duct stent appears to have not inferior outcomes of procedural complications, mortality, hospital and ICU stay, and pulmonary artery growth in selected patients compared with a surgical shunt. TRIAL REGISTRATION: CRD42019147672.


Assuntos
Procedimento de Blalock-Taussig , Cateterismo Cardíaco/instrumentação , Permeabilidade do Canal Arterial/terapia , Cardiopatias Congênitas/terapia , Hemodinâmica , Artéria Pulmonar/cirurgia , Circulação Pulmonar , Stents , Procedimento de Blalock-Taussig/efeitos adversos , Procedimento de Blalock-Taussig/mortalidade , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/mortalidade , Criança , Pré-Escolar , Permeabilidade do Canal Arterial/diagnóstico por imagem , Permeabilidade do Canal Arterial/mortalidade , Permeabilidade do Canal Arterial/fisiopatologia , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/mortalidade , Cardiopatias Congênitas/fisiopatologia , Humanos , Lactente , Recém-Nascido , Tempo de Internação , Masculino , Cuidados Paliativos , Artéria Pulmonar/anormalidades , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/crescimento & desenvolvimento , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento
13.
Phytomedicine ; 81: 153367, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33260064

RESUMO

BACKGROUND: Treatments for coronavirus disease 2019 (COVID-19) are limited by suboptimal efficacy. METHODS: From January 30, 2020 to March 23, 2020, we conducted a non-randomised controlled trial, in which all adult patients with laboratory-confirmed COVID-19 were assigned to three groups non-randomly and given supportive treatments: Group A, Lopinavir-Ritonavir; Group B, Huashi Baidu Formula (a Chinese medicineformula made by the China Academy of Chinese Medical Sciences to treat COVID-19, which is now in the clinical trial period) and Lopinavir-Ritonavir; and Group C, Huashi Baidu Formula. The use of antibiotics, antiviruses, and corticosteroids was permitted in Group A and B. Traditional Chinese medicine injections were permitted in Group C. The primary outcomes were clinical remission time (interval from admission to the first time the patient tested negatively for novel coronavirus or an obvious improvement was observed from chest CT) and clinical remission rate (number of patients whose clinical time was within 16 days/total number of patients). RESULTS: A total of 60 adult patients with COVID-19 were enrolled at sites in Wuhan, China, and the sample size of each group was 20. In Groups A, B and C, the clinical remission rates were 95.0%%(19/20), 100.0%%(20/20) and 100.0%%(20/20), respectively. Compared with Groups A and B, the clinical remission time of Group C was significantly shorter (5.9 days vs. 10.8 days, p < 0.05; 5.9 days vs. 9.7 days, p < 0.05). There was no significant difference among Groups A, B, and C in terms of the time taken to be released from quarantine. The clinical biochemical indicators and safety indexes showed no significant differences among the three groups. CONCLUSIONS: Our findings suggest that Lopinavir-Ritonavir has some efficacy in the treatment of COVID-19, and the Huashi Baidu Formula might enhance this effect to an extent. In addition, superiority was displayed in the treatment of COVID-19 through a combination of the Huashi Baidu Formula and traditional Chinese medicine injection. In future, well-designed prospective double-blinded randomised control trials are required to confirm our findings.


Assuntos
Antivirais/uso terapêutico , COVID-19/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Lopinavir/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , COVID-19/diagnóstico por imagem , Combinação de Medicamentos , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Lopinavir/efeitos adversos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Segurança do Paciente , Estudos Prospectivos , Ritonavir/efeitos adversos , Tórax/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Resultado do Tratamento
14.
Heart Fail Rev ; 26(1): 91-100, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31845048

RESUMO

We aimed to assess the efficacy and safety of pulmonary vasodilators in patients after the Fontan procedure. The PubMed, EMBASE, and Cochrane Library databases were searched through November 2019 for studies comparing pulmonary vasodilators and controls in Fontan patients. The variables assessed included change in pulmonary resistance, heart function, exercise capacity, quality of life, mortality, and adverse events after drug administration. A random/fixed effects model was used to assess the mean difference (MD)/risk ratio (RR) with 95% confidence intervals (CIs). Subgroup analysis was stratified by drug category. In total, 449 Fontan patients from 13 studies were included. Pooled estimates of the change in pulmonary arterial pressure (MD, - 1.07; 95% CI, - 2.75 to 0.60; p = 0.21), New York Heart Association class (MD, - 0.57; 95% CI, - 1.41 to 0.28; p = 0.19), peak oxygen consumption (MD, 1.46; 95% CI, 0.01 to 2.90; p = 0.05), Short Form 36 (MD, 1.39; 95% CI, - 0.62 to 3.39; p = 0.17), mortality (RR, 0.37; 95% CI, 0.08 to 1.65; p = 0.19), and any adverse event (RR, 0.94; 95% CI, 0.71 to 1.24; p = 0.64) were not significantly different between the drug and control groups. Likewise, most results of the subgroup analysis revealed no significant between-group differences. Pulmonary vasodilator therapy appears to be safe, but not beneficial, in the categories of pulmonary resistance, heart function, or quality of life in patients who have undergone a Fontan procedure. No significant evidence was found to confirm that most pulmonary vasodilators could improve exercise capacity in Fontan patients.

15.
Nat Genet ; 52(12): 1384-1396, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33139953

RESUMO

Trimethylated histone H3 lysine 27 (H3K27me3) regulates gene repression, cell-fate determination and differentiation. We report that a conserved bromo-adjacent homology (BAH) module of BAHCC1 (BAHCC1BAH) 'recognizes' H3K27me3 specifically and enforces silencing of H3K27me3-demarcated genes in mammalian cells. Biochemical, structural and integrated chromatin immunoprecipitation-sequencing-based analyses demonstrate that direct readout of H3K27me3 by BAHCC1 is achieved through a hydrophobic trimethyl-L-lysine-binding 'cage' formed by BAHCC1BAH, mediating colocalization of BAHCC1 and H3K27me3-marked genes. BAHCC1 is highly expressed in human acute leukemia and interacts with transcriptional corepressors. In leukemia, depletion of BAHCC1, or disruption of the BAHCC1BAH-H3K27me3 interaction, causes derepression of H3K27me3-targeted genes that are involved in tumor suppression and cell differentiation, leading to suppression of oncogenesis. In mice, introduction of a germline mutation at Bahcc1 to disrupt its H3K27me3 engagement causes partial postnatal lethality, supporting a role in development. This study identifies an H3K27me3-directed transduction pathway in mammals that relies on a conserved BAH 'reader'.


Assuntos
Carcinogênese/genética , Código das Histonas/genética , Histonas/metabolismo , Leucemia/genética , Proteínas/genética , Proteínas/metabolismo , Animais , Diferenciação Celular/genética , Linhagem Celular Tumoral , Imunoprecipitação da Cromatina , Regulação da Expressão Gênica/genética , Inativação Gênica/fisiologia , Células HEK293 , Células HeLa , Humanos , Células Jurkat , Leucemia/patologia , Metilação , Camundongos , Camundongos Transgênicos , Transplante de Neoplasias , Processamento de Proteína Pós-Traducional/genética , Transplante Heterólogo
16.
Artigo em Inglês | MEDLINE | ID: mdl-33101442

RESUMO

Cardiovascular disease (CVD) is the number one threat that seriously endangers human health. However, the mechanism of their occurrence is not completely clear. Increasing studies showed that mitochondrial dysfunction is closely related to CVD. Possible causes of mitochondrial dysfunction include oxidative stress, Ca2+ disorder, mitochondrial DNA mutations, and reduction of mitochondrial biosynthesis, all of which are closely related to the development of CVD. At present, traditional Chinese medicine (TCM) is widely used in the treatment of CVD. TCM has the therapeutic characteristics of multitargets and multipathways. Studies have shown that TCM can treat CVD by protecting mitochondrial function. Via systematic literature review, the results show that the specific mechanisms include antioxidant stress, regulation of calcium homeostasis, antiapoptosis, and regulation of mitochondrial biosynthesis. This article describes the relationship between mitochondrial dysfunction and CVD, summarizes the TCM commonly used for the treatment of CVD in recent years, and focuses on the regulatory effect of TCM on mitochondrial function.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33062029

RESUMO

Cardiovascular disease is one of the main human health risks, and the incidence is increasing. Salidroside is an important bioactive component of Rhodiola rosea L., which is used to treat Alzheimer's disease, tumor, depression, and other diseases. Recent studies have shown that salidroside has therapeutic effects, to some degree, in cardiovascular diseases via an antioxidative mechanism. However, evidence-based clinical data supporting the effectiveness of salidroside in the treatment of cardiovascular diseases are limited. In this review, we discuss the effects of salidroside on cardiovascular risk factors and cardiovascular diseases and highlight potential antioxidant therapeutic strategies.

18.
Front Cell Dev Biol ; 8: 722, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850838

RESUMO

Background: OLFM3 (olfactomedin-3) is a member of the olfactomedin domain family, which has been found to stimulate the formation and adhesion of tight cell connections and to regulate cytoskeleton formation and cell migration. Differences in the gene coding for OLFM3 have been found between patients with epilepsy and controls. However, the exact role of OLFM3 in epilepsy has not been thoroughly investigated. Methods: Biochemical methods were used to assess OLFM3 expression and localization in the cortex of patients with temporal lobe epilepsy and in the hippocampus and cortex of epileptic mice. Electrophysiological recordings were used to measure the role of OLFM3 in regulating hippocampal excitability in a model of magnesium-free-induced seizure in vitro. Behavioral experiments were performed in a pentylenetetrazol (PTZ)-induced seizure model, and electroencephalograms (EEGs) were recorded in the chronic phase of the kainic acid (KA)-induced epilepsy model in vivo. OLFM3 and its interaction with AMPAR (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor) subunits were analyzed by co-immunoprecipitation. Results: The expression of OLFM3 was increased in the cortex of patients with temporal lobe epilepsy and in the hippocampus and cortex of epileptic mice compared with controls. Interestingly, lentivirus-mediated overexpression of OLFM3 in the hippocampus increased the susceptibility of mice to PTZ-induced seizures, and OLFM3 knockdown had the opposite effect. OLFM3 affected AMPAR currents in a brain-slice model of epileptiform activity induced by Mg2+-free medium. We found that OLFM3 co-immunoprecipitation with GluA1 and GluA2. Furthermore, downregulation or overexpression of OLFM3 in the hippocampus affected the membrane expression of GluA1 and GluA2 in epileptic mice. Conclusion: These findings reveal that OLFM3 may enhance seizure activity by interacting with GluA1 and GluA2, potentially indicating a molecular mechanism for new therapeutic strategies.

19.
Pediatr Cardiol ; 41(7): 1376-1385, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32494877

RESUMO

We performed this meta-analysis to assess the safety and efficacy of tracheoplasty for patients with pulmonary artery sling (PAS) and tracheal stenosis. Published studies that included surgical treatment of PAS and tracheal stenosis with and without tracheoplasty were identified by searching the PubMed, EMBASE, and Cochrane Library databases until May 2020. The outcomes assessed included postoperative ventilation time, early and late mortality, and follow-up respiratory symptoms. The mean difference (MD)/risk ratio (RR) with 95% confidence intervals (CI) was estimated with a random-effects/fixed-effects model. Subgroup analysis was performed stratified by percentage of patients with tracheal rings. A total of eight studies comprising 219 patients with PAS accompanied by tracheal stenosis were included. The pooled estimates of postoperative ventilation time (MD 17.68, 95% CI 6.38 to 28.98, p < 0.01) and early mortality (RR 3.93, 95% CI 1.55 to 9.95, p < 0.01) favored the repair-only group. Late mortality (RR 1.33, 95% CI 0.48 to 3.68, p = 0.58) and respiratory symptoms (RR 1.51, 95% CI 0.50 to 4.57, p = 0.47) at follow-up showed no significant differences between the groups with repair-only and repair with tracheoplasty. The same results were found in subgroup analyses. For the surgical treatment of PAS with tracheal stenosis, repair without tracheoplasty appears to result in shorter postoperative ventilation time and lower early mortality, with no increase in late mortality or respiratory symptoms at follow-up, compared with concomitant tracheoplasty.


Assuntos
Cardiopatias Congênitas/cirurgia , Artéria Pulmonar/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Traqueia/cirurgia , Estenose Traqueal/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Razão de Chances , Artéria Pulmonar/anormalidades , Procedimentos Cirúrgicos Reconstrutivos/efeitos adversos , Respiração Artificial , Resultado do Tratamento
20.
Subst Use Misuse ; 55(9): 1493-1500, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569531

RESUMO

Background: Research suggests that young working students are at higher risk for substance use. However, most studies have focused on students from middle-class families, with few investigations conducted on substance use by students from low-income families. Objective: To examine the associations between work experience and betel nut, alcohol, or tobacco (BAT) use among Taiwanese students from low-income families. Methods: The data for this cross-sectional study were derived from the fourth wave of the Taiwan Panel Study of Children and Youth survey which provides primary data on low-income families. A total of 3,350 low-income students aged 12-25 years old from middle school to university participated. The χ2 test was performed to examine differences in sociodemographic characteristics and BAT use between employed and unemployed students. Multivariate logistic regression was used to examine the associations between work status, work intensity, monthly income, occupation, and BAT use. Results: Employed students displayed higher BAT use than those who were unemployed. Increased BAT use was also associated with higher work intensity (except for betel nut use), higher monthly income, and specific occupations (such as service or manual work). Conclusions: Employment is independently associated with a higher risk of BAT use among low-income Taiwanese students. Work intensity and specific occupational fields may offer insights into formulating relevant preventive measures for these students.


Assuntos
Areca , Universidades , Adolescente , Adulto , Criança , Estudos Transversais , Humanos , Instituições Acadêmicas , Estudantes , Taiwan/epidemiologia , Uso de Tabaco/epidemiologia , Adulto Jovem
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