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1.
Europace ; 26(5)2024 May 02.
Article in English | MEDLINE | ID: mdl-38637325

ABSTRACT

AIMS: Left atrial appendage electrical isolation (LAAEI) has demonstrated a significant enhancement in the success rate of atrial fibrillation (AF) ablation. Nevertheless, concerns persist about the safety of LAAEI, particularly regarding alterations in left atrial appendage (LAA) flow velocity and the potential risks of thrombus. This study aimed to assess the efficacy and safety of LAAEI, investigating changes in LAA flow velocity in canines. METHODS AND RESULTS: The study comprised a total of 10 canines. The LAAEI procedure used by a 23 mm cryoballoon of the second generation was conducted at least 180 s. Intracardiac ultrasonography (ICE) was employed to quantify the velocity flow of the LAA both prior to and following LAAEI. Following a 3-month period, subsequent evaluations were performed to assess the LAA velocity flow and the potential reconnection. Histopathological examination was conducted. Left atrial appendage electrical isolation was effectively accomplished in all canines, resulting in a 100% acute success rate (10/10). The flow velocity in the LAA showed a notable reduction during LAAEI as compared with the values before the ablation procedure (53.12 ± 5.89 vs. 42.01 ± 9.22 cm/s, P = 0.007). After the follow-up, reconnection was observed in four canines, leading to a success rate of LAAEI of 60% (6/10). The flow velocity in the LAA was consistently lower (53.12 ± 5.89 vs. 44.33 ± 10.49 cm/s, P = 0.006), and no blood clot development was observed. The histopathological study indicated that there was consistent and complete injury to the LAA, affecting all layers of its wall. The injured tissue was subsequently replaced by fibrous tissue. CONCLUSION: The feasibility of using cryoballoon ablation for LAAEI was confirmed in canines, leading to a significant reduction of LAA flow velocity after ablation. Some restoration of LAA flow velocity after ablation may be linked to the passive movement of the LAA and potential reconnecting. However, this conclusion is limited to animal study; more clinical data are needed to further illustrate the safety and accessibility of LAAEI in humans.


Subject(s)
Atrial Appendage , Atrial Fibrillation , Cryosurgery , Dogs , Animals , Atrial Appendage/surgery , Cryosurgery/methods , Cryosurgery/adverse effects , Cryosurgery/instrumentation , Atrial Fibrillation/surgery , Atrial Fibrillation/physiopathology , Atrial Fibrillation/diagnosis , Equipment Design , Blood Flow Velocity , Treatment Outcome , Male
2.
Eur J Clin Invest ; 52(9): e13804, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35506324

ABSTRACT

BACKGROUND: Vascular aging is an important risk factor for various cardiovascular diseases. Transcription factor krüppel-like factor 4 (KLF4) could regulate the phenotypic transformation of the vascular smooth muscle cell (VSMC) in the pathogenesis of aortic diseases. The present study aimed to explore the role and mechanism of KLF4 in angiotensin II (Ang II)-induced VSMC senescence. METHODS: The VSMC senescence mouse model was induced by sustained release of Ang II (1.0 µg/kg/min) for 4 weeks. The premature senescent VSMCs were induced by Ang II (0.1 µmol/L) for 72 h. Cellular senescence was measured by senescence-associated ß-galactosidase (SA-ß-gal) activity and p53/p16 expression. The autophagic activity was evaluated by autophagic flux and autophagic marker expression. RESULTS: The expression of KLF4 was extremely increased in abdominal aorta tissues after 1-week Ang II stimulation (p < .01) but began to decrease in later periods. Decreased expression of KLF4 was also detected in premature senescent VSMCs. Overexpression of KLF4 could enhance the antisenescence ability of VSMCs. Significantly decreased amounts of SA-ß-gal-positive cells and lower p53/p16 expression were detected in KLF4-overexpressing VSMCs (p < .01). Next, telomerase reverse transcriptase (TERT) was identified as a direct downstream target of KLF4 in VSMCs. Overexpression of KLF4 in VSMCs prevented the decreased expression of TERT under Ang II stimulation condition, which could in turn, contribute to the enhanced autophagic activity, and ultimately to the improved antisenescence ability of VSMCs. CONCLUSIONS: Our results demonstrated that overexpression of KLF4 prevented Ang II-induced VSMC senescence by promoting TERT-mediated autophagy. These findings provided novel potential targets for the prevention and therapy of vascular aging.


Subject(s)
Angiotensin II , Autophagy , Kruppel-Like Factor 4 , Muscle, Smooth, Vascular , Angiotensin II/pharmacology , Animals , Cells, Cultured , Cellular Senescence , Kruppel-Like Factor 4/metabolism , Mice , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Tumor Suppressor Protein p53
3.
Cell Mol Biol Lett ; 27(1): 85, 2022 Oct 08.
Article in English | MEDLINE | ID: mdl-36209049

ABSTRACT

BACKGROUND: Diabetic cardiomyopathy (DCM) results from pathological changes in cardiac structure and function caused by diabetes. Excessive oxidative stress is an important feature of DCM pathogenesis. MicroRNAs (miRNAs) are key regulators of oxidative stress in the cardiovascular system. In the present study, we screened for the expression of oxidative stress-responsive miRNAs in the development of DCM. Furthermore, we aimed to explore the mechanism and therapeutic potential of miR-92a-2-5p in preventing diabetes-induced myocardial damage. METHODS: An experimental type 2 diabetic (T2DM) rat model was induced using a high-fat diet and low-dose streptozotocin (30 mg/kg). Oxidative stress injury in cardiomyocytes was induced by high glucose (33 mmol/L). Oxidative stress-responsive miRNAs were screened by quantitative real-time PCR. Intervention with miR-92a-2-5p was accomplished by tail vein injection of agomiR in vivo or adenovirus transfection in vitro. RESULTS: The expression of miR-92a-2-5p in the heart tissues was significantly decreased in the T2DM group. Decreased miR-92a-2-5p expression was also detected in high glucose-stimulated cardiomyocytes. Overexpression of miR-92a-2-5p attenuated cardiomyocyte oxidative stress injury, as demonstrated by increased glutathione level, and reduced reactive oxygen species accumulation, malondialdehyde and apoptosis levels. MAPK interacting serine/threonine kinase 2 (MKNK2) was verified as a novel target of miR-92a-2-5p. Overexpression of miR-92a-2-5p in cardiomyocytes significantly inhibited MKNK2 expression, leading to decreased phosphorylation of p38-MAPK signaling, which, in turn, ameliorated cardiomyocyte oxidative stress injury. Additionally, diabetes-induced myocardial damage was significantly alleviated by the injection of miR-92a-2-5p agomiR, which manifested as a significant improvement in myocardial remodeling and function. CONCLUSIONS: miR-92a-2-5p plays an important role in cardiac oxidative stress, and may serve as a therapeutic target in DCM.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Cardiomyopathies , MicroRNAs , Animals , Apoptosis , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Diabetic Cardiomyopathies/genetics , Diabetic Cardiomyopathies/metabolism , Diabetic Cardiomyopathies/pathology , Glucose/metabolism , Glutathione/metabolism , Malondialdehyde/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Myocytes, Cardiac/metabolism , Oxidative Stress , Protein Serine-Threonine Kinases , Rats , Reactive Oxygen Species/metabolism , Serine/metabolism , Streptozocin/metabolism
4.
Toxicol Ind Health ; 37(7): 391-397, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34047658

ABSTRACT

Di-2-ethylhexyl phthalate (DEHP) is a type of plasticizer widely used in industry. It is well-known for its toxic effects to endocrine and reproductive systems and has been detected in amniotic fluid and placenta. In the present study, we explored the effects of DEHP on heart development by using zebrafish as a model organism. DEHP (0.02 pg) was injected into the yolk sac of zebrafish embryos at the one-cell stage. No significant difference was found in embryonic lethality between control and DEHP groups at 1-day postfertilization (dpf), but mortality significantly increased in DEHP groups at 2 and 3 dpf. The average heart rate was significantly reduced in the surviving DEHP-treated zebrafish larvae at 3 and 4 dpf. In addition, massive pericardial edema was found in DEHP-treated zebrafish (12.6 ± 1.5%), which was significantly higher than that of the control group. Serious heart looping disorder was also observed in DEHP-treated larvae, mainly manifested with an elongated atrial-ventricular distance. Moreover, the expression of heart development transcription factors was affected by DEHP injection. Real-time polymerase chain reaction confirmed that five transcription factors (hand2, tp53, mef2c, esr1, and tbx18) were significantly downregulated in the DEHP group at 2 dpf, and three transcription factors (zic3, tcf21, and gata4) were significantly upregulated. Our results emphasize the need for the development of a nontoxic plasticizer to prevent possible deleterious effects on humans and other life-forms.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors/drug effects , Diethylhexyl Phthalate/toxicity , Embryo, Nonmammalian/drug effects , Heart/drug effects , Heart/growth & development , Membrane Glycoproteins/drug effects , Zebrafish Proteins/drug effects , Zebrafish/growth & development , Animals , Embryonic Development/drug effects , Humans , Occupational Exposure/adverse effects , Organogenesis/drug effects , Plasticizers/toxicity , Water Pollutants, Chemical/toxicity
5.
J Cell Biochem ; 120(10): 18278-18287, 2019 10.
Article in English | MEDLINE | ID: mdl-31144399

ABSTRACT

Hyperglycemia in diabetic patients would cause cardiomyocytes oxidative stress and apoptosis due to the excessive reactive oxygen species (ROS) accumulation, leading to progressive deterioration of cardiac structure and function. Long noncoding RNAs (lncRNAs) play essential roles on controlling oxidative stress and apoptotic activity. In the present study, RNA sequencing was used to detect the differentially expressed lncRNAs during high glucose-induced cardiomyocytes oxidative stress and apoptosis. A total of 306/400 lncRNAs were identified as differentially expressed, including 156/198 lncRNAs with increased expression and 150/202 lncRNAs with decreased expression at 24 hours/48 hours after high-glucose stimulation respectively. Among these dysregulated lncRNAs, 45 lncRNAs were consistently differentially expressed in cardiomyocytes at both two time points after high-glucose stimulation. Twenty lncRNAs were upregulated and 25 lncRNAs were downregulated at both 24 hours and 48 hours, respectively. The top three upregulated lncRNAs, NONRATT029805.2, NONRATT007560.2, and NONRATT002486.2 were selected for functional studies to determine the role in oxidative stress-related apoptosis. The results showed that inhibition of non-ratt007560.2 could abate the formation of ROS and reduce apoptosis, suggesting NONRATT007560.2 might play critical roles in the development of cardiomyopathy. The dysregulated lncRNAs might participate in regulating cardiomyocytes oxidative stress and apoptosis. These findings would be important theoretical and experimental basis for investigation on diabetic cardiomyopathy pathogenesis.


Subject(s)
Apoptosis/drug effects , Gene Expression Profiling , Glucose/pharmacology , Myocytes, Cardiac/drug effects , Oxidative Stress , RNA, Long Noncoding/genetics , Animals , Animals, Newborn , Apoptosis/genetics , Cells, Cultured , Diabetic Cardiomyopathies/diagnosis , Diabetic Cardiomyopathies/genetics , Diabetic Cardiomyopathies/metabolism , Dose-Response Relationship, Drug , Down-Regulation/drug effects , Humans , Myocytes, Cardiac/metabolism , RNA Interference , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Sequence Analysis, RNA , Up-Regulation/drug effects
6.
J Electrocardiol ; 51(6): 1121-1123, 2018.
Article in English | MEDLINE | ID: mdl-30497742

ABSTRACT

We herein describe a case of an acute pericarditis, in which type 1 Brugada phenocopy (BrP) was documented. The patient was referred to our hospital due to severe chest pain. The twelve-lead electrocardiogram (ECG) on admission showed type 1 Brugada ECG pattern (coved-type) in the precordial leads. Echocardiography only showed mild pericardial effusion. However, his ST segment elevation returned to normal and chest discomfort disappeared 3 weeks later. Our report addresses the possibility that the coved-type ST-segment elevation cannot be a sensitive finding for Brugada syndrome (BrS). Detailed tests are anyway needed to make appropriate diagnostic and therapeutic decisions.


Subject(s)
Brugada Syndrome/diagnosis , Electrocardiography , Pericarditis/diagnosis , Acute Disease , Brugada Syndrome/diagnostic imaging , Chest Pain/etiology , Diagnosis, Differential , Echocardiography , Humans , Male , Pericarditis/complications , Phenotype , Sensitivity and Specificity , Young Adult
7.
Mol Cell Biochem ; 419(1-2): 165-76, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27426491

ABSTRACT

Vascular dysfunction including vascular remodeling and endothelial dysfunction in hypertension often results in poor clinical outcomes and increased risk of vascular accidents. We investigate the effect of treatment with soluble receptor for advanced glycation end products (sRAGE) on vascular dysfunction in spontaneously hypertensive rats (SHR). Firstly, the aortic AGE/RAGE pathway was investigated in SHR. Secondly, SHR received intraperitoneal injections of sRAGE daily for 4 weeks. Effect of sRAGE against vascular dysfunction in SHR and underlying mechanism was investigated. SHR aortas exhibited enhanced activity of aldose reductase, reduced activity of glyoxalase 1, accumulation of methylglyoxal and AGE, and upregulated expression of RAGE. Treatment of SHR with sRAGE had no significant effect on blood pressure, but alleviated aortic hypertrophy and endothelial dysfunction. In vitro, treatment with sRAGE reversed the effect of incubation with AGE on proliferation of smooth muscle cells and endothelial function. Treatment of SHR with sRAGE abated oxidative stress, suppressed inflammation and NF-κB activation, improved the balance between Ang II and Ang-(1-7) through reducing angiotensin-converting enzyme (ACE) activity and enhancing ACE2 expression, and upregulated peroxisome proliferator-activated receptor gamma (PPAR-γ) expression in aortas. In conclusion, treatment with sRAGE alleviated vascular adverse remodeling in SHR, possibly via suppression of oxidative stress and inflammation, improvement in RAS balance, and activation of PPAR-γ pathway.


Subject(s)
Aorta/metabolism , Aortic Diseases/metabolism , Oxidative Stress/drug effects , Receptor for Advanced Glycation End Products , Vascular Remodeling/drug effects , Angiotensin I/metabolism , Angiotensin-Converting Enzyme 2 , Animals , Aorta/pathology , Aortic Diseases/chemically induced , Aortic Diseases/pathology , Gene Expression Regulation, Enzymologic/drug effects , Glycation End Products, Advanced/metabolism , Lactoylglutathione Lyase/metabolism , NF-kappa B/metabolism , PPAR gamma/metabolism , Peptide Fragments/metabolism , Peptidyl-Dipeptidase A/biosynthesis , Rats , Rats, Inbred SHR , Reactive Oxygen Species/metabolism
8.
Wei Sheng Yan Jiu ; 45(6): 897-905, 2016 Nov.
Article in Zh | MEDLINE | ID: mdl-29903070

ABSTRACT

OBJECTIVE: To identify the expression levels of miR-1897-3p, miR-690 and miR-7a-5p in mice liver tissues with a high fat diet-induced insulin resistance using a stem-loop reverse transcriptional real-time fluorescence quantitative PCR( RT-q PCR)method, and predict microRNAs( miRNAs)-regulated target genes and their functions to investigate the relationship between insulin resistance and differentially expressed miRNAs. METHODS: The total of 30 liver tissue samples were obtained from 15 normal control mice and 15 test mice with a high fat diet-induced insulin resistance. The stemloop reverse transcriptional primers and the primers of real-time PCR were designed to establish a RT-q PCR method, and then the expression levels of miR-1897-3p, miR-690 and miR-7a-5p of 30 liver tissue samples were detected and analyzed. Using bioinformatics methods, the target genes of differentially expressed miRNAs were predicted, and then enriched gene ontology( GO), related signal pathways and target gene protein-target gene protein interactions were analyzed, respectively. RESULTS: Compared with control group, the expression levels of miR-1897-3p, miR-690 and miR-7a-5p detected by RT-q PCR in the group with a high-fat diet-induced insulin resistance were significantly decreased( P < 0. 05), which exhibited the similar pattern of down regulation to the previous microarray results. Bioinformatics analysis results showed that a total of 16 target genes were regulated by two differentially expressed miRNAs. Among of the 16 target gene protein, 8 proteins had interactions with ≥4 proteins. Rac1, Rhoa, Prkcz, Tgfbr2, Itch and Ube2d3 protein were located in the central node of the network, and they were associated or cross-linking with insulin signaling pathway. CONCLUSION: miR-1897-3p, miR-690 and miR-7a-5p in liver tissues may be involved in the physiopathologic process of insulin resistance, which may be affect the normal insulin signaling pathway cascade by regulating the expression of target genes.


Subject(s)
Computational Biology , Diet, High-Fat/adverse effects , Gene Expression Profiling , Insulin Resistance/genetics , Liver/physiology , MicroRNAs/genetics , Animals , Mice
9.
Pest Manag Sci ; 80(9): 4665-4674, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38884421

ABSTRACT

BACKGROUND: The presence of barnyardgrass poses a threat to global food security by reducing rice yields. Currently, herbicides are primarily applied for weed management. However, the effectiveness of herbicide deposition and uptake on barnyardgrass is limited as a consequence of the high wax content on leaves, low water solubility and extreme lipophilicity of herbicides. Therefore, it is imperative to develop novel formulations for efficient delivery of herbicides to improve herbicidal activity and reduce dosage. RESULTS: We successfully prepared nanosuspension(s) (NS) of quinclorac through the wet media milling technique. This NS demonstrates excellent physical stability and maintains nanoscale during dose transfer. The deposition concentration and uptake concentration of NS on barnyardgrass were 3.84-4.47- and 2.11-2.58-fold greater than those traditional formulations, respectively. Moreover, the NS exhibited enhanced herbicidal activity against barnyardgrass at half the dosage required by conventional formulations without compromising rice safety. CONCLUSIONS: These findings suggest that NS can effectively facilitate the delivery of hydrophobic and poorly water-soluble herbicide active ingredients, thereby enhancing their deposition, uptake and bioactivity. This study expands the potential application of NS in pesticide delivery, which can provide valuable support for optimizing pesticide utilization, improving economic efficiency and mitigating environmental risks. © 2024 Society of Chemical Industry.


Subject(s)
Herbicides , Quinolines , Herbicides/chemistry , Herbicides/pharmacology , Quinolines/chemistry , Quinolines/pharmacology , Suspensions , Nanoparticles/chemistry , Echinochloa/drug effects , Weed Control/methods
10.
Nanomicro Lett ; 16(1): 193, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38743342

ABSTRACT

The flourishing progress in nanotechnology offers boundless opportunities for agriculture, particularly in the realm of nanopesticides research and development. However, concerns have been raised regarding the human and environmental safety issues stemming from the unrestrained use of non-therapeutic nanomaterials in nanopesticides. It is also important to consider whether the current development strategy of nanopesticides based on nanocarriers can strike a balance between investment and return, and if the complex material composition genuinely improves the efficiency, safety, and circularity of nanopesticides. Herein, we introduced the concept of nanopesticides with minimizing carriers (NMC) prepared through prodrug design and molecular self-assembly emerging as practical tools to address the current limitations, and compared it with nanopesticides employing non-therapeutic nanomaterials as carriers (NNC). We further summarized the current development strategy of NMC and examined potential challenges in its preparation, performance, and production. Overall, we asserted that the development of NMC systems can serve as the innovative driving force catalyzing a green and efficient revolution in nanopesticides, offering a way out of the current predicament.

11.
Int J Biol Macromol ; 247: 125688, 2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37423439

ABSTRACT

Lead is highly persistent and toxic in soil, hindering plant growth. Microspheres are a novel, functional, and slow-release preparation commonly used for controlled release of agricultural chemicals. However, their application in the remediation of Pb-contaminated soil has not been studied; furthermore, the remediation mechanism involved has not been systematically assessed. Herein, we evaluated the Pb stress mitigation ability of sodium alginate-gelatin-polyvinyl pyrrolidone composite microspheres. Microspheres effectively attenuated the Pb toxic effect on cucumber seedlings. Furthermore, they boosted cucumber growth, increased peroxidase activity, and chlorophyll content, while reducing malondialdehyde content in leaves. Microspheres promoted Pb enrichment in cucumber, especially in roots (about 4.5 times). They also improved soil physicochemical properties, promoted enzyme activity, and increased soil available Pb concentration in the short term. In addition, microspheres selectively enriched functional (heavy metal-tolerating and plant growth promoting) bacteria to adapt to and resist Pb stress by improving soil properties and nutrients. These results indicated that even a small amount (0.025-0.3 %) of microspheres can significantly reduce the adverse effects of Pb on plants, soil, and bacterial communities. Composite microspheres have shown great value in Pb remediation, and their application potential in phytoremediation is also worth evaluating to expand the application.


Subject(s)
Cucumis sativus , Microbiota , Soil Pollutants , Gelatin , Polyvinyls , Soil Pollutants/toxicity , Soil/chemistry , Lead/toxicity , Microspheres , Plants , Bacteria , Alginates/pharmacology , Pyrrolidinones , Biodegradation, Environmental
12.
Chemosphere ; 313: 137539, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36521750

ABSTRACT

Excessive copper (Cu) concentrations pose significant health risks to both plants and humans. In this study, sodium alginate (SA)-gelatin (GEL)-polyvinyl pyrrolidone (PVP)- embedded dinotefuran (DIN) microspheres were prepared using spray-drying technology. The loading content and encapsulation efficiency of optimal microspheres determined by physical modifications were 19.77% and 99.32%, respectively. In addition, the microspheres showed variable stimuli-responsive controlled release capacities in different temperatures and types of soil, as well as showed better control efficiency of larvae of Protaetia brevitarsis at pesticide application in the early stage, with the potential ability to control pest outbreaks at high temperatures. In addition, blank microspheres improved the growth and physiological activity of cucumber seedlings, reduced copper content in leaves, increased soil nutrient content, and prevented soil acidification. Further, the use of blank microspheres increased the relative abundance of soil beneficial functional bacteria communities, which mediate heavy metal (HM) immobilization/tolerance and promote plant growth. Redundancy analysis (RDA) and Spearman correlation analysis showed that these beneficial functional bacteria were mainly positively correlated with soil EC, A-N, and N-N. In summary, this study showed that the technique of combining physically modified carrier materials with pesticides has the potential to reduce Cu contamination in the surrounding agricultural soil during pesticide application, thereby reducing Cu uptake by crops.


Subject(s)
Pesticides , Soil Pollutants , Humans , Copper/toxicity , Pesticides/toxicity , Soil , Microspheres , Delayed-Action Preparations , Soil Pollutants/toxicity , Alginates
13.
Front Cardiovasc Med ; 10: 1183787, 2023.
Article in English | MEDLINE | ID: mdl-37745096

ABSTRACT

Pregnancy predisposes to arrhythmias in females due to physiological changes in the cardiovascular system, enhanced activity of the sympathetic nervous system (SNS), and changes in the endocrine system, regardless of whether there exist cardiovascular diseases before the pregnancy. Tachyarrhythmias may present for the first time or worsen persistently during pregnancy, potentially leading to maternal heart failure and sudden death, as well as some adverse fetal outcomes such as growth restriction, distress, premature birth, and stillbirth. Radiofrequency ablation (RFA) is one of the most important therapeutic methods for tachyarrhythmias. According to the 2019 European Society of Cardiology (ESC) guidelines, RFA in pregnant women should preferably be performed without x-rays. Since the 2000s, 3D mapping technique has rapidly developed, laying the foundation for cardiac electrophysiology examination free from x-rays. Ventricular arrhythmia originating from the left coronary cusp (LCC) is not common in clinic. RFA is challenging in the treatment of this type of disease due to the anatomical feature that the opening of the left main coronary artery is localized in the LCC.

14.
Oxid Med Cell Longev ; 2023: 3271057, 2023.
Article in English | MEDLINE | ID: mdl-36785789

ABSTRACT

Background: The pharmacological mechanism of the traditional Chinese medicine formula-Jijiu Huiyang decoction (JJHYD), which contains several herbal medicines for the treatment of chronic heart failure (CHF), is yet unknown. Method and Materials. The main active components of JJHYD were analyzed by ultrahigh-performance liquid chromatography-mass spectrometry (UHPLC-MS/MS). The target genes of JJHYD and CHF were retrieved through multiple databases, a drug-ingredient-target-disease network was created, and KEGG enrichment and GO analyses were carried out. The binding ability of paeonol and Glycogen Synthase Kinase-3 alpha (GSK3A) was confirmed by molecular docking. CHF animal model and cell model were constructed. The effects of paeonol on cardiac dysfunction, myocardial hypertrophy, cardiac lipid accumulation, and myocardial apoptosis were detected by echocardiography, histopathology, and flow cytometry, respectively. The effects of paeonol on the expression of myocardial hypertrophy index, GSK3A, and genes or proteins related to the PPARα pathway were determined by qRT-PCR or western blot. Result: UHPLC-MS/MS analysis combined with database verification showed a total of 227 chemical components in JJHYD, among which paeonol was the one with heart-protective roles and had the highest content. Paeonol alleviated isoproterenol-induced cardiac lipid accumulation, cardiac hypertrophy, and myocardial dysfunction and inhibited the activation of the PPARα pathway, while overexpression of GSK3A reversed these effects of paeonol. However, the reversal effects of GSK3A overexpression could be offset by siPPARα. Conclusion: As the main active substance of JJHYD, paeonol participates in the protection of CHF by targeting the GSK3A/PPARα signaling pathway to reduce lipid toxicity.


Subject(s)
Drugs, Chinese Herbal , Heart Failure , Animals , Isoproterenol/adverse effects , PPAR alpha/genetics , Molecular Docking Simulation , Tandem Mass Spectrometry , Heart Failure/chemically induced , Heart Failure/drug therapy , Protein Serine-Threonine Kinases , Cardiomegaly/drug therapy , Lipids , Drugs, Chinese Herbal/adverse effects
15.
Carbohydr Polym ; 277: 118880, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-34893283

ABSTRACT

Neonicotinoid-based pesticides are extensively used owing to their broad insecticidal spectrum and activity. We developed neonicotinoid dinotefuran (DIN)-loaded chitosan-gelatin microspheres using a spray-drying technology, resulting in a pH- and temperature-responsive controlled-release system. Upon introducing chitosan into the triple-helix structure of gelatin, the physically modified gelatin microspheres became smooth, round, and solid, improving their thermal storage stability. The spray-drying parameters were optimized using three-dimensional surface plots. When scaled up under optimal conditions, the corresponding loading content and encapsulation efficiency were 21.5% and 98.17%, respectively. Compared with commercial dinotefuran granules, our biodegradable composite carriers achieved the immobilization of dinotefuran to reduce pesticide leaching by 5.57-19.89% in soil, improved the soil half-life of DIN, and improved its cumulative absorption by plants. Therefore, the microspheres showed better efficacy against Trialeurodes vaporariorum. Our results confirm that this simple approach can improve the utilization efficiency of neonicotinoids, decrease leaching loss, and promote ecological safety.

16.
Circ J ; 75(3): 703-9, 2011.
Article in English | MEDLINE | ID: mdl-21266788

ABSTRACT

BACKGROUND: Several microRNAs (miRNAs) have been reported to regulate cardiovascular biological and pathological processes through inhibiting the translation of certain RNA transcripts. However, little is known about the association between miRNAs and vascular smooth muscle cell (VSMC) proliferation. The aim was to investigate the role of miRNAs in VSMC growth and the potential mechanism. METHODS AND RESULTS: Primary VSMCs were isolated from the medial layer of the thoracic aorta obtained from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). miRNA microarrays were used to analyze the difference in miRNA expression between VSMCs of SHR and WKY rats and were validated using TaqMan real-time PCR. Of the potentially related genes under the influence of let-7d identified through literature search, KRAS was verified by western blot and functionally analyzed using miRNA mimics transfection and analysis of transfectants by cell enumeration was made using CCK-8 and flow cytometric analysis of cell cycle progression. let-7d-transfected VSMCs from SHR, WKY and human coronary arteries expressed significantly lower amounts of KRAS protein, displayed reduced cell growth and led to a greater number of cells in the G1 phase than the G2/M phases of the cell cycle. CONCLUSIONS: let-7d was significantly downregulated in VSMCs as an important regulator of cell proliferation. RAS might be involved in the proliferation regulation by let-7d.


Subject(s)
Cell Proliferation , MicroRNAs/metabolism , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/metabolism , Proto-Oncogene Proteins p21(ras)/metabolism , Animals , Aorta, Thoracic/cytology , Aorta, Thoracic/metabolism , Cell Cycle/physiology , Cells, Cultured , Female , MicroRNAs/genetics , Models, Animal , Proto-Oncogene Proteins p21(ras)/genetics , Rats , Rats, Inbred SHR , Rats, Inbred WKY , Sincalide/genetics , Sincalide/metabolism , Transfection
17.
Sci Rep ; 11(1): 8633, 2021 04 21.
Article in English | MEDLINE | ID: mdl-33883631

ABSTRACT

Electrocardiographic and electrophysiological characteristics of VAs originating from the vicinity of the TA are not fully understood. Hence, 104 patients (mean age 52.6 ± 17.9 years; 62 male) with VAs originating from the vicinity of the TA were enrolled. After electrophysiological evaluation and ablation, data were compared among those patients. The ECGs and the correction of the ECGs based on the long axis of the heart calculated from the chest X-Ray were also analyzed. VAs originating from the vicinity of TA had distinctive ECG characteristics that were useful for identifying the precise origin. Our localization algorithm adjusted by the angle between the cardiac long axis and the horizon was found to be accurate in predicting the exact ablation site in 92.3% (n = 96) cases. Logistic regression analysis showed fractionated electrograms, the magnitudes of the local atrial electrograms and a/V ratio were critical factors for successful ablation. Among the 104 patients with VAs, complete elimination could be achieved by RFCA in 96 patients (success rate 92.3%) during a follow-up period of 35.2 ± 19.6 months. This study suggests that the ablation site could be localized by ECG analysis adjusted by the angle between the cardiac long axis and the horizon. Fractionated electrograms, the magnitudes of the local atrial electrograms and a/V ratio were demonstrated to be critical factors for successful ablation.


Subject(s)
Electrophysiological Phenomena/physiology , Heart Conduction System/physiology , Heart Ventricles/physiopathology , Tachycardia, Ventricular/physiopathology , Tricuspid Valve/physiopathology , Adolescent , Adult , Aged , Aged, 80 and over , Algorithms , Cardiac Electrophysiology/methods , Catheter Ablation/methods , Electrocardiography/methods , Female , Humans , Male , Middle Aged , Treatment Outcome , Ventricular Premature Complexes/physiopathology , Young Adult
18.
J Mater Chem B ; 9(3): 783-792, 2021 01 28.
Article in English | MEDLINE | ID: mdl-33333547

ABSTRACT

Pesticides play a very important role in pest control and plant protection. However, they can be limited by a tendency to cause ecological system damage due to significant losses into the environment. To increase pesticide utilization efficiency, we developed highly leaf-adhesive avermectin nanocapsules (Av-pH-cat@CS) with pH-responsive controlled release properties. The Av-pH-cat@CS nanocapsules displayed good thermal stability and photostability in response to UV light irradiation. The Av-pH-cat@CS nanocapsules could be disrupted at low pH and they exhibited excellent controlled release in response to pH, which improved the release of avermectins. In addition, the Av-pH-cat@CS nanocapsules were highly adhesive to crop leaves as a result of strong hydrogen bonding, which prolonged the retention time on crop leaves. The Av-pH-cat@CS nanocapsules with pH-responsive release and strong leaf adhesion improved the control efficacy and enhanced the utilization efficiency. Our findings offer a promising approach to prolonging pesticide duration on crop leaves and improving the utilization efficiency.


Subject(s)
Adhesives/chemistry , Antiprotozoal Agents/chemistry , Ivermectin/analogs & derivatives , Nanocapsules/chemistry , Pesticides/chemistry , Adhesives/chemical synthesis , Antiprotozoal Agents/chemical synthesis , Drug Liberation , Hydrogen Bonding , Hydrogen-Ion Concentration , Ivermectin/chemical synthesis , Ivermectin/chemistry , Molecular Structure , Particle Size , Pesticides/chemical synthesis , Plant Leaves/chemistry , Surface Properties , Time Factors , Zea mays/chemistry
19.
Biochem Biophys Res Commun ; 394(1): 184-8, 2010 Mar 26.
Article in English | MEDLINE | ID: mdl-20188071

ABSTRACT

OBJECTIVE: Current biomarkers cannot completely distinguish sepsis from systemic inflammatory response syndrome (SIRS) caused by other non-infectious diseases. Circulating microRNAs (miRNAs) are promising biomarkers for several diseases, but their correlation with sepsis is not totally clarified. METHODS: Seven miRNAs related to inflammation or infection were included in the present study. Serum miRNA expression was investigated in 50 patients diagnosed with sepsis, 30 patients with SIRS and 20 healthy controls to evaluate the diagnostic and prognostic value. Expression levels of serum miRNAs were determined by quantitative PCR using the Qiagen miScript system. Serum CRP and IL-6 levels were determined by enzyme linked immunosorbent assay. RESULTS: Serum miR-146a and miR-223 were significantly reduced in septic patients compared with SIRS patients and healthy controls. The areas under the receiver operating characteristic curve of miR-146a, miR-223 and IL-6 were 0.858, 0.804 and 0.785, respectively. CONCLUSION: Serum miR-146a and miR-223 might serve as new biomarkers for sepsis with high specificity and sensitivity. (ClinicalTrials.gov number, NCT00862290.).


Subject(s)
MicroRNAs/blood , Sepsis/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Adult , Aged , Biomarkers/blood , Diagnosis, Differential , Female , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Sepsis/blood , Systemic Inflammatory Response Syndrome/blood
20.
PLoS One ; 15(2): e0228817, 2020.
Article in English | MEDLINE | ID: mdl-32032382

ABSTRACT

Abamectin is a common biocide used to control agricultural insect pests. However, the water insolubility of abamectin may result in extra organic solvent introduced in the environment. To solve this issue, it is desirable to develop nanoformulations to encapsulate abamectin with environment-friendly polymers. In this study, two polylactic acid based abamectin nanoformulations were prepared. The average particle sizes, measured by dynamic light scattering and transmission electron microscope, were 240 nm and 150 nm, respectively. The insecticidal activity of these nano-formulated abamectin was examined in the laboratory on the pea aphid, Acyrthosiphon pisum (Hemiptera: Aphididae). The acute toxicity of nano-formulated abamectin on non-target aphid predator Adalia bipunctata (Coleoptera: Coccinellidae) was also evaluated by topical, residual and oral exposure. The two nano-formulated abamectin had comparable insecticidal effect with commercial abamectin formulation against the pea aphid. Taking median lethal concentration (LC50) as the toxicological endpoint, nanoformulations had higher contact toxicity and lower oral toxicity to first-instar larvae of the predator A. bipunctata. These results are expected to contribute to the application of solvent-free nano-formulated pesticides that comply with the integrated pest management (IPM) strategies.


Subject(s)
Aphids/drug effects , Coleoptera/drug effects , Insecticides/toxicity , Ivermectin/analogs & derivatives , Nanostructures/chemistry , Polyesters/chemistry , Animals , Aphids/growth & development , Coleoptera/growth & development , Drug Compounding , Insecticides/chemistry , Ivermectin/chemistry , Ivermectin/toxicity , Lethal Dose 50 , Particle Size
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