RESUMEN
BACKGROUND: Circular RNAs are enriched in cardiac tissue and play important roles in the pathogenesis of heart diseases. In this study, we aimed to investigate the regulatory mechanism of a conserved heart-enriched circRNA, circPan3, in cardiac hypertrophy. METHODS: Cardiac hypertrophy was induced by isoproterenol. The progression of cardiomyocyte hypertrophy was assessed by sarcomere organization staining, cell surface area measurement, and expression levels of cardiac hypertrophy markers. RNA interactions were detected by RNA pull-down assays, and methylated RNA immunoprecipitation was used to detect m6A level. RESULTS: The expression of circPan3 was downregulated in an isoproterenol-induced cardiac hypertrophy model. Forced expression of circPan3 attenuated cardiomyocyte hypertrophy, while inhibition of circPan3 aggravated cardiomyocyte hypertrophy. Mechanistically, circPan3 was an endogenous sponge of miR-320-3p without affecting miR-320-3p levels. It elevated the expression of HSP20 by endogenously interacting with miR-320-3p. In addition, circPan3 was N6-methylated. Stimulation by isoproterenol downregulated the m6A eraser ALKBH5, resulting in N6-methylation and destabilization of circPan3. CONCLUSIONS: Our research is the first to report that circPan3 has an antihypertrophic effect in cardiomyocytes and revealed a novel circPan3-modulated signalling pathway involved in cardiac hypertrophy. CircPan3 inhibits cardiac hypertrophy by targeting the miR-320-3p/HSP20 axis and is regulated by ALKBH5-mediated N6-methylation. This pathway could provide potential therapeutic targets for cardiac hypertrophy.
Asunto(s)
MicroARNs , ARN Circular , Humanos , ARN Circular/genética , ARN Circular/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Isoproterenol , Cardiomegalia/genética , Cardiomegalia/patología , Miocitos Cardíacos/metabolismoRESUMEN
Based on the 87 original publications only from quartiles 1 and 2 of Journal Citation Report (JCR) collected by the major academic databases (Science Direct, Web of Science, PubMed, and Wiley) in 2022, the frontier of toxicology studies in zebrafish model is summarized. Herewith, a total of six aspects is covered such as developmental, neurological, cardiovascular, hepatic, reproductive, and immunizing toxicities. The tested samples involve chemicals, drugs, new environmental pollutants, nanomaterials, and its derivatives, along with those related mechanisms. This report may provide a frontier focus benefit to researchers engaging in a zebrafish model for environment, medicine, food, and other fields.
Asunto(s)
Contaminantes Ambientales , Pez Cebra , Animales , ReproducciónRESUMEN
Different poplar varieties vary in their tolerance to certain pathogens. However, knowledge about molecular regulation and critical responses of resistant poplars during pathogen infection remains scarce. To investigate adaptive responses to canker disease caused by the bacterium Lonsdalea populi, we screened three poplar varieties with contrasting tolerance, including Populus deltoides. 'Zhonglin 2025' (2025), Populus × Euramericana. '74/76' (107) and Populus tomentosa cv 'henan' (P. tomentosa). Transcriptomic analysis revealed significant changes in the expression levels of defence-related genes in different poplar varieties in response to infection, which reshaped the PTI and ETI processes. Intriguingly, photosynthesis-related genes were found to be highly expressed in the resistant variety, whereas the opposite was observed in the susceptible variety. Susceptible poplars maintained the activation of defence-related genes during early period of onset, which restricted the expression of photosynthesis-related and auxin signal-related genes. Furthermore, combined with metabolomic analysis, differences in the content of antibacterial substances and key differentially expressed genes in phenylpropane and flavonoid biosynthesis pathways were identified. Delayed induction of catechin in the susceptible variety and it's in vitro antibacterial activity were considered to be one of the important reasons for the differences in resistance to L. populi compared with the resistant variety, which is of practical interest for tree breeding. Moreover, the trade-off between growth and defence observed among the three poplar varieties during infection provides new insights into the multilevel regulatory circuits in tree-pathogen interactions.
Asunto(s)
MetabolómicaRESUMEN
Phospholipids are lipids that constitute the basic structure of cell membranes. In-depth research has shown that in addition to supporting cell structures, phospholipids participate in multiple cellular processes, including promoting cell signal transduction, guiding protein translocation, activating enzymatic activity, and eliminating dysfunctional/redundant organelles/cells. Diabetes is a chronic metabolic disease with a complicated etiology and pathology. Studies have shown that the level of certain phospholipids, for example, the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) in liver tissue, is negatively associated with insulin sensitivity. In addition, PS is a phospholipid exhibiting extensive cellular functions in diabetes. For this review, we analyzed many PS studies focusing on diabetes and insulin sensitivity in recent years and found that PS participates in controlling insulin secretion, regulating insulin signaling transduction, and participating in the progression of diabetic complications by mediating coagulation disorders in the microvasculature or targeting mitochondria. Moreover, PS supplements in food and PS-containing liposomes have been shown to protect against type 1 and type 2 diabetes (T1D and T2D, respectively) in animal studies. Therefore, by summarizing the regulatory roles played by PS in diabetes and the potential of successfully using PS or PS-containing liposomes for diabetic therapy, we hope to provide new ideas for further research into the mechanisms of diabetes and for drug development for treating diabetes and its complications.
Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Animales , Liposomas , Fosfatidilserinas , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Fosfolípidos/metabolismo , FosfatidiletanolaminasRESUMEN
Small extracellular vesicles (sEVs) are generated by almost all cell types. They have a bilayer membrane structure that is similar to cell membranes. Thus, the phospholipids contained in sEVs are the main components of cell membranes and function as structural support elements. However, as in-depth research on sEV membrane components is conducted, some phospholipids have been found to participate in cellular biological processes and function as targets for cell-cell communication. Currently, sEVs are being developed as part of drug delivery systems and diagnostic factors for various diseases, especially neurodegenerative diseases and cancer. An understanding of the physiological and pathological roles of sEV phospholipids in cellular processes is essential for their future medical application. In this review, the authors discuss phospholipid components in sEVs of different origins and summarize the roles of phospholipids in sEV biogenesis. The authors further collect the current knowledge on the functional roles of sEV phospholipids in cell-cell communication and bioactivities as signals regulating neurodegenerative diseases and cancer and the possibility of using sEV phospholipids as biomarkers or in drug delivery systems for cancer diagnosis and treatment. Knowledge of sEV phospholipids is important to help us identify directions for future studies.
Asunto(s)
Vesículas Extracelulares , Neoplasias , Enfermedades Neurodegenerativas , Sistemas de Liberación de Medicamentos , Humanos , Enfermedades Neurodegenerativas/diagnóstico , Fosfolípidos/uso terapéuticoRESUMEN
To integrate the active advantages of 18ß-glycyrrhetinic acid (18ß-GA) and emodin, improve bioavailability, increase efficiency, and reduce toxicity, a one-step innovative synthetic route was set up for the first time: 4-dimethylaminopyridine (DMAP) was used as catalyst, 1-ethyl-(3-dimethylaminopropyl)carboimide hydrochloride (EDCI) as condensation agent, dry dichloromethane (DCM) as solvent at 25 °C for 12â h, the three target products were obtained and purified by high performance liquid chromatography (HPLC), the chemical structures of them were characterized by nuclear magnetic resonance (NMR) technique and high resolution electron ionization mass spectrometry (HREI-MS), namely, 18ß-glycyrrhetinic acid-3-emodin ester (1, yield 78.83 %, known), di-18ß-glycyrrhetinic acid-1-emodin ester (2, yield 6.49 %, new), and di-18ß-glycyrrhetinic acid-8-emodin ester (3, yield 1.81 %, new). To estimate their effects of the products on toxicity in zebrafish embryos and juvenile fishes, the two precursors and three target products were assayed involving in hatching rate, survival rate, morphology, heart rate, and apoptosis of cardiomyocytes. The results showed that the target products enhanced the hatching and survival rate of zebrafish embryos, decreased the malformation rate and the apoptosis of cardiomyocytes. It should be suggested that the one-step synthesis route with high yield makes the industrial application of the target products possible due to significantly reduced toxicity. The two new by-products provide potential candidates for the applications of pharmaceutical industry in the future.
Asunto(s)
Emodina , Ácido Glicirretínico , Animales , Ésteres/farmacología , Ácido Glicirretínico/análogos & derivados , Ácido Glicirretínico/química , Ácido Glicirretínico/farmacología , Pez CebraRESUMEN
Non-coding RNAs (ncRNAs) play essential roles in plants by modulating the expression of genes at the transcriptional or post-transcriptional level. In recent years, ncRNAs have been recognized as crucial regulators for growth and development in forest trees, and ncRNAs that respond to various abiotic stresses are now under intense study. In this review, we summarized recent advances in the understanding of abiotic stress-responsive microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in forest trees. Furthermore, we analyzed the intersection of miRNAs, and epigenetic modified ncRNAs of forest trees in response to abiotic stress. In particular, the abiotic stress-related lncRNA/circRNA-miRNA-mRNA regulatory network of forest trees was explored.
Asunto(s)
MicroARNs , ARN Largo no Codificante , Bosques , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , ARN no Traducido/genética , Estrés Fisiológico/genética , Árboles/genética , Árboles/metabolismoRESUMEN
Anthracyclines, such as doxorubicin (DOX), are well known for their high efficacy in treating multiple cancers, but their clinical usage is limited due to their potential to induce fatal cardiotoxicity. Such detrimental effects significantly impact the overall physical condition or even induce the morbidity and mortality of cancer survivors. Therefore, it is extremely important to understand the mechanisms of DOX-induced cardiotoxicity to develop methods for the early detection of cytotoxicity and therapeutic applications. Studies have shown that many molecular events are involved in DOX-induced cardiotoxicity. However, the precise mechanisms are still not completely understood. Recently, noncoding RNAs (ncRNAs) have been extensively studied in a diverse range of regulatory roles in cellular physiological and pathological processes. With respect to their roles in DOX-induced cardiotoxicity, microRNAs (miRNAs) are the most widely studied, and studies have focused on the regulatory roles of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), which have been shown to have significant functions in the cardiovascular system. Recent discoveries on the roles of ncRNAs in DOX-induced cardiotoxicity have prompted extensive interest in exploring candidate ncRNAs for utilization as potential therapeutic targets and/or diagnostic biomarkers. This review presents the frontier studies on the roles of ncRNAs in DOX-induced cardiotoxicity, addresses the possibility and prospects of using ncRNAs as diagnostic biomarkers or therapeutic targets, and discusses the possible reasons for related discrepancies and limitations of their use.
Asunto(s)
Cardiotoxicidad/metabolismo , Doxorrubicina/toxicidad , MicroARNs/metabolismo , ARN Circular/metabolismo , ARN Largo no Codificante/metabolismo , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Biomarcadores/metabolismo , Cardiotoxicidad/tratamiento farmacológico , Humanos , MicroARNs/uso terapéuticoRESUMEN
Abnormal mitochondrial fission and mitophagy participate in the pathogenesis of many cardiovascular diseases. Baicalein is a key active component in the roots of traditional Chinese medicinal herb Scutellaria baicalensis Georgi. It has been reported that baicalein can resist cardiotoxicity induced by several stress, but the mechanisms of baicalein operate in the protection of cardiomyocytes need to be researched further. Here we report that baicalein can promote cell survival under oxidative stress by up-regulating the expression level of MARCH5 in cardiomyocytes. Pre-treatment cells or mice with baicalein can stabilize the expression of MARCH5, which plays a crucial role in the regulation of mitochondrial network and mitophagy. Overexpressed MARCH5 is able to against H2 O2 and ischaemia/reperfusion (I/R) stress by suppressing mitochondrial fission and enhancing mitophagy, and then attenuate cells apoptosis. Altogether, our present study investigated that baicalein exerts a protective effect through regulating KLF4-MARCH5-Drp1 pathway, our research also provided a novel theoretical basis for the clinical application of baicalein.
Asunto(s)
Apoptosis/efectos de los fármacos , Flavanonas/farmacología , Peróxido de Hidrógeno/toxicidad , Mitocondrias/metabolismo , Proteínas Mitocondriales/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Estrés Oxidativo/efectos de los fármacos , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Cardiotónicos/farmacología , Línea Celular , Flavanonas/uso terapéutico , Factor 4 Similar a Kruppel , Ratones , Mitocondrias/efectos de los fármacos , Dinámicas Mitocondriales/efectos de los fármacos , Mitofagia/efectos de los fármacos , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Miocitos Cardíacos/efectos de los fármacos , Estabilidad Proteica/efectos de los fármacosRESUMEN
Abnormal autophagy plays critical roles in the structure and function of the pulmonary vasculature. Cyclophilin A (CyPA) can be secreted from cells in response to hypoxia and oxidative stress, which are involved in inducing autophagy and regulating the function of endothelial cells in pulmonary arterial hypertension. Honokiol is a small molecule natural compound; it has many bioactivities, such as antitumor, anti-inflammatory, antioxidant and antiangiogenic properties, but how honokiol mediates autophagy in pulmonary arterial hypertension is unclear. Rat' lungs gavaged with honokiol were examined for autophagy via western blot and fluorescence microscopy. In addition, western blot, quantitative RT-PCR and immunofluorescence were employed to test the expression of CyPA and autophagy markers in pulmonary artery endothelial cells (PAECs). Small interfering RNA targeting CyPA (si-CyPA) was used to knockdown the expression of CyPA, and then autophagy was tested with mRFP-GFP-LC3 fluorescence microscopy and western blot. We found that honokiol could reduce the expression of CyPA and autophagy markers in vivo and in vitro. Furthermore, autophagy was also down-regulated by si-CyPA. Taken together, we revealed a novel mechanism by which honokiol regulates autophagy. The results revealed that honokiol can alleviate autophagy and pulmonary arterial hypertension regulated by CyPA in PAECs.
Asunto(s)
Autofagia/efectos de los fármacos , Compuestos de Bifenilo/farmacología , Ciclofilina A/metabolismo , Hipertensión Pulmonar/tratamiento farmacológico , Lignanos/farmacología , Animales , Western Blotting , Bovinos , Células Cultivadas , Células Endoteliales/efectos de los fármacos , Células Endoteliales/metabolismo , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Hipertensión Pulmonar/patología , Masculino , Microscopía Fluorescente , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Ratas , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Although many studies have estimated the association between the butyrylcholinesterase (BCHE) K variant and Alzheimer's disease (AD) risk, the results are still controversial. We thus conducted this meta-analysis. MATERIAL/METHODS: We searched NCBI, Medline, Web of Science, and Embase databases to find all eligible studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of the association. RESULTS: We found a significant association between BCHE K variant and AD risk (OR=1.20; 95% CI 1.03-1.39; P=0.02). In the stratified analysis by ethnicity, we observed a significant association between BCHE K variant and AD risk in Asians (OR=1.32; 95% CI 1.02-1.72; P=0.04). However, no significant association between BCHE K variant and AD risk in Caucasians was found (OR=1.14; 95% CI 0.95-1.37; P=0.16). When stratified by the age of AD onset, we found that late-onset AD (LOAD) was significantly associated with BCHE K variant (OR=1.44; 95% CI 1.05-1.97; P=0.02). No significant association between BCHE K variant and early-onset AD (EOAD) risk was observed (OR=1.16; 95% CI 0.89-1.51; P=0.27). Compared with non-APOE ε4 and non-BCHE K carriers, no significant association between BCHE K variant and AD risk was found (OR=1.11; 95% CI 0.91-1.35; P=0.30). However, APOE ε4 carriers showed increased AD risk in both non-BCHE K carriers (OR=2.81; 95% CI 1.75-4.51; P=0.0001) and BCHE K carriers (OR=3.31; 95% CI 1.82-6.02; P=0.0001). CONCLUSIONS: The results of this meta-analysis indicate that BCHE K variant might be associated with AD risk.
Asunto(s)
Enfermedad de Alzheimer/genética , Butirilcolinesterasa/genética , Polimorfismo de Nucleótido Simple , Edad de Inicio , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/enzimología , Enfermedad de Alzheimer/etnología , Apolipoproteína E4/genética , Pueblo Asiatico/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Oportunidad Relativa , Sesgo de Publicación , Riesgo , Sensibilidad y Especificidad , Población Blanca/genéticaRESUMEN
The response of cardiac fibroblast proliferation to detrimental stimuli is one of the main pathological factors causing heart remodeling. Reactive oxygen species (ROS) mediate the proliferation of cardiac fibroblasts. However, the exact molecular mechanism remains unclear. In vivo, we examined the oxidative modification of miRNAs with miRNA immunoprecipitation with O8G in animal models of cardiac fibrosis induced by Ang II injection or ischemiaâreperfusion injury. Furthermore, in vitro, we constructed oxidation-modified miR-30c and investigated its effects on the proliferation of cardiac fibroblasts. Additionally, luciferase reporter assays were used to identify the target of oxidized miR-30c. We found that miR-30c oxidation was modified by Ang II and PDGF treatment and mediated by excess ROS. We demonstrated that oxidative modification of G to O8G occurred at positions 4 and 5 of the 5' end of miR-30c (4,5-oxo-miR-30c), and this modification promoted cardiac fibroblast proliferation. Furthermore, CDKN2C is a negative regulator of cardiac fibroblast proliferation. 4,5-oxo-miR-30c misrecognizes CDKN2C mRNA, resulting in a reduction in protein expression. Oxidized miR-30c promotes cardiac fibroblast proliferation by mismatch mRNA of CDKN2C.
Asunto(s)
Proliferación Celular , Fibroblastos , MicroARNs , Oxidación-Reducción , MicroARNs/genética , MicroARNs/metabolismo , Animales , Fibroblastos/metabolismo , Fibroblastos/citología , Especies Reactivas de Oxígeno/metabolismo , Miocardio/metabolismo , Miocardio/citología , Angiotensina II/farmacología , Ratas , Masculino , Ratones , FibrosisRESUMEN
Background: Interpretation of ultrasound findings of thyroid nodules is subjective and labor-intensive for radiologists. Artificial intelligence (AI) is a relatively objective and efficient technology. We aimed to establish a fully automatic detection and diagnosis system for thyroid nodules based on AI technology by analyzing ultrasound video sequences. Patients and Methods: We prospectively acquired dynamic ultrasound videos of 1067 thyroid nodules (804 for training and 263 for validation) from December 2018 to January 2021. All the patients underwent hemithyroidectomy or total thyroidectomy. Dynamic ultrasound videos were used to develop an AI system consisting of two deep learning models that could automatically detect and diagnose thyroid nodules. Average precision (AP) was used to estimate the performance of the detection model. The area under the receiver operating characteristic curve (AUC) was used to measure the performance of the diagnostic model. Results: Location and shape were accurately detected with a high AP of 0.914 in the validation cohort. The AUC of the diagnostic model was 0.953 in the validation cohort. The sensitivity and specificity of junior and senior radiologists were 76.9% vs 78.3% and 68.4% vs 81.1%, respectively. The diagnostic performance of the AI diagnostic model was superior to that of junior radiologists (P = 0.016) and was not significantly different from that of senior radiologists (P = 0.281). Conclusion: We established a fully automatic detection and diagnosis system for thyroid nodules based on ultrasound video using an AI approach that can be conveniently applied to optimize the management of patients with thyroid nodules.
RESUMEN
Deer antler velvet, with kidney tonifying, promoting the production of essence and blood, strengthening tendons and bones, not only has a thousand-year medicinal history but also its modern pharmacology mainly focuses on its active polypeptides on motor, nerve, and immune systems. The purpose of this report is to fill the gap in the comprehensive, systematic, and detailed review of polypeptides during the recent 30 years (1992-2023). The research method was to review 53 pharmacological articles from the Public Medicine, Web of science, ACS, and Science Direct database sources by searching the keywords "pilose antler," "deer velvet," "Pilose Antler Peptide (PAP) and Velvet Antler Polypeptide (VAP)." The results showed that deer antler polypeptides (DAPs), by regulating EGF, EGFR, MAPK, P38, ERK, NF-κB, Wnt, PI3K, Akt, MMP, AMPK, Stir1, NLRP3, HO-1, Nrf, Rho, TLR, TGF-ß, Smad, Ang II, etc., revealed their effects on seven system-related diseases and their mechanisms, including osteoarthritis, intervertebral disc degeneration, osteoporosis, Alzheimer's, Parkinson's, triple-negative breast cancer, liver injury, liver fibrosis, cardiovascular disease, acute lung injury, and late-onset hypogonadism. In conclusion, DAPs have good effects on motor and other system-related diseases, but the secondary and tertiary structures of DAPs (0.5-1800 KDa) need to be further elucidated, and the structure-activity relationship study is still unavailable and needs to be covered. It is expected that this review may provide the necessary literature support for further research. The activities and mechanisms of polypeptides from the past 30 years (1992-2023) are summarized covering seven systems, related diseases, and its regulatory genes and proteins.
Asunto(s)
Cuernos de Venado , Ciervos , Osteoartritis , Osteoporosis , Animales , Péptidos/farmacología , Cuernos de Venado/químicaRESUMEN
Fungi, such as Trichophyton rubrum (T. rubrum) and Microsporum canis Bodin Anamorph (M. canis Bodin Anamorph) are the main pathogens of dermatophysis. According to ancient books records, Rumex japonicus Houtt. (RJH) has a miraculous effect on the treatment of dermatophysis. To reveal the anti-fungi (T. rubrum and M. canis Bodin Anamorph) components and its mechanism of the Rumex japonicus Houtt. The vinegar extraction and alcohol precipitation, HPLC and nuclear magnetic resonance spectroscopy (NMR) were employed for analyzing the chemical compositions of RJH; in vitro anti-fungal experiment was investigated including test the minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC), spore germination rate, nucleic acid, protein leakage rate, biofilm structure, and the mechanism of anti-fungal and anti-fungal biofilms in RJH. Seven anthraquinones and their glycoside compounds were obtained in this study respectively, such as chrysophanol, physcion, aloe-emodin, emodin, rhein, emodin-8-O-ß-D-glucoside and chrysophanol-8-O-ß-D-glucoside. In vitro anti-fungal experiment results showed that RJH extracts have good anti-fungal activity for dermatophytic fungi. Among them, the MIC of the rhein, emodin and aloe-emodin against T. rubrum are 1.9 µg/ml, 3.9 µg/ml and 15.6 µg/ml, respectively; the MIC of emodin and aloe-emodin against M. canis Bodin Anamorph are 7.8 µg/ml and 62.5 µg/ml, respectively. In addition, its active components can inhibit fungal spore germination and the formation of bud tube, change cell membrane permeability, prevent hyphal growth, destroy biofilm structure, and down-regulate the expression of agglutinin-like sequence family 1 of the adhesion phase of biofilm growth. The study shows that RJH play a fungicidal role.
Asunto(s)
Antraquinonas , Antifúngicos , Biopelículas , Glicósidos , Pruebas de Sensibilidad Microbiana , Microsporum , Rumex , Antraquinonas/farmacología , Antraquinonas/química , Antraquinonas/aislamiento & purificación , Rumex/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Glicósidos/farmacología , Glicósidos/química , Microsporum/efectos de los fármacos , Biopelículas/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/química , Emodina/farmacología , Emodina/química , Emodina/análogos & derivados , ArthrodermataceaeRESUMEN
3,4,5-Trimethoxycinnamic acid (TMCA), methyl 3,4,5-trimethoxycinnamate (M-TMCA) and p-methoxycinnamic acid (PMCA) have been identified as the major bioactive components in the serum collected from rats treated with oral administration of Polygalae Radix ("YuanZhi," the roots of Polygala tenuifolia WILLD.), a traditional Chinese medicine used to relieve insomnia, anxiety and heart palpitation. The present study was designed to investigate its direct electrophysiological effects on isolated ventricular myocytes from rabbits. Whole-cell configuration of the patch-clamp technique was used to measure action potential (AP) and membrane currents in single ventricular myocytes enzymatically isolated from adult rabbit hearts. Ca(2+) transients were recorded in myocytes loaded with the Ca(2+) indicator Fluo-4AM. Among three bioactive substances of Polygala metabolites, only M-TMCA (15-30 µM) significantly shortened action potential duration at 50% and 90% repolarization (APD(50) and APD(90)) in cardiomyocytes in a concentration-dependent and a reversible manner. M-TMCA also inhibited L-type calcium current (I(Ca,L)), but showed effect on neither transient outward potassium current (I(to)) nor steady-state potassium current (I(K,SS)). Furthermore, M-TMCA abolished isoprenaline plus BayK8644-induced early afterdepolarizations (EADs) and suppressed delayed afterdepolarizations (DADs) and triggered activities (TAs). This potential anti-arrhythmic effects were likely attributed by the inhibition of I(Ca,L) and the suppression of intracellular Ca(2+) transients, which consequently suppress the generation of transient inward current (I(ti)). These findings suggest that M-TMCA may protect the heart from arrhythmias via its inhibitory effect on calcium channel.
Asunto(s)
Antiarrítmicos/farmacología , Cinamatos/farmacología , Miocitos Cardíacos/efectos de los fármacos , Polygala , Animales , Medicamentos Herbarios Chinos/farmacología , Masculino , Miocitos Cardíacos/fisiología , Raíces de Plantas , ConejosRESUMEN
PURPOSE: Diabetic cardiomyopathy is the leading cause of death in diabetic patients, and the mechanism by which factors other than hyperglycemia contribute to the development of diabetic cardiomyopathy is unknown. Serum small extracellular vesicles (sEVs) carry bioactive proteins or nuclei, which enter into remote tissues and modulate cell functions. However, in diabetic conditions, the changes of lipids carried by sEVs has not been identified. Our study aims to explore the changes of lipids in sEVs in diabetic patients with cardiovascular disease, we hope to provide new ideas for understanding the role of lipid metabolism in the pathogenesis of diabetic cardiomyopathy. METHODS: SEVs samples derived from serum of health controls (Ctrl), diabetic patients without cardiovascular diseases (DM), and diabetic patients with cardiovascular diseases (DM-CAD) were used for lipidomics analysis. Because AC16 cells are also treated with those sEVs to confirm the entrance of cells and effects on insulin sensitivity, a lipidomics analysis on cells was also performed. RESULTS AND CONCLUSIONS: In this study, we found that docosahexaenoic acid (DHA)-triacylglycerides of sEVs from serums of DM-CAD patients decreased significantly, and those sEVs could enter into AC16 cells and diminish insulin sensitivity. In addition, DHA-triacylglycerides were also decreased in cells treated with sEVs from DM-CAD. Therefore, DHA-triacylglycerides carried by sEVs may mediate intercellular signaling and be associated with the incidence of diabetic cardiovascular complications.
Asunto(s)
Enfermedades Cardiovasculares , Diabetes Mellitus , Cardiomiopatías Diabéticas , Vesículas Extracelulares , Resistencia a la Insulina , Humanos , Ácidos Docosahexaenoicos , TriglicéridosRESUMEN
Parapanteles hypsidrae (Wilkinson, 1928) and Protapanteles immunis (Haliday, 1834) are the most important parasitic wasps of Ectropis grisescens Warren and Ectropis obliqua (Prout). We sequenced and annotated the mitochondrial genomes of Pa. hyposidrae and Pr. immunis, which are 17,063 bp and 16,397 bp in length, respectively, and possess 37 mitochondrial genes. We discovered two novel types of gene rearrangement, the local inversion of nad4L in Pa. hyposidrae and the remote inversion of the block cox3-nad3-nad5-nad4 in Pr. immunis, within the mitogenomes of Braconidae. The phylogenetic analysis supported the subfamily Microgastrinae is a monophyletic group, but the tribes Apantelini and Cotesiini within this subfamily are paraphyletic groups.
Asunto(s)
Genoma Mitocondrial , Avispas , Animales , Avispas/genética , Filogenia , Secuencia de Bases , Reordenamiento GénicoRESUMEN
O-linked-ß-N-acetylglucosamine (O-GlcNAcylation) is a distinctive posttranslational protein modification involving the coordinated action of O-GlcNAc transferase and O-GlcNAcase, primarily targeting serine or threonine residues in various proteins. This modification impacts protein functionality, influencing stability, protein-protein interactions, and localization. Its interaction with other modifications such as phosphorylation and ubiquitination is becoming increasingly evident. Dysregulation of O-GlcNAcylation is associated with numerous human diseases, including diabetes, nervous system degeneration, and cancers. This review extensively explores the regulatory mechanisms of O-GlcNAcylation, its effects on cellular physiology, and its role in the pathogenesis of diseases. It examines the implications of aberrant O-GlcNAcylation in diabetes and tumorigenesis, highlighting novel insights into its potential role in cardiovascular diseases. The review also discusses the interplay of O-GlcNAcylation with other protein modifications and its impact on cell growth and metabolism. By synthesizing current research, this review elucidates the multifaceted roles of O-GlcNAcylation, providing a comprehensive reference for future studies. It underscores the potential of targeting the O-GlcNAcylation cycle in developing novel therapeutic strategies for various pathologies.
RESUMEN
Trees are inevitably attacked by different kinds of pathogens in their life. However, little is known about the regulatory factors in poplar response to different pathogen infections. MicroRNA159 (miR159) is a highly conserved microRNA (miRNA) in plants and regulates plant development and stress responses. Here, transgenic poplar overexpressing pto-miR159a (OX-159) showed antagonistic regulation mode to poplar stem disease caused by fungi Cytospora chrysosperma and bacteria Lonsdalea populi. OX-159 lines exhibited a higher susceptibility after inoculation with bacterium L. populi, whereas enhanced disease resistance to necrotrophic fungi C. chrysosperma compared with wild-type (WT) poplars. Intriguingly, further disease assay found that OX159 line rendered the poplar susceptible to hemi-biotrophic fungi Colletotrichum gloeosporioide, exhibiting larger necrosis and lower ROS accumulation than WT lines. Transcriptome analyses revealed that more down-regulated differentially expressed genes with disease-resistant domains in OX-159 line compared with WT line. Moreover, the central mediator NPR1 of salicylic acid (SA) pathway showed a decrease in expression level, while jasmonic acid/ethylene (JA/ET) signal pathway marker genes ERF, as well as PR3, MPK3, and MPK6 genes showed an increase level in OX159-2 and OX159-5 compared with WT lines. Further spatio-temporal expression analysis revealed JA/ET signaling was involved in the dynamic response process to C. gloeosporioides in WT and OX159 lines. These results demonstrate that overexpression of pto-miR159a resulted in the crosstalk changes of the downstream hub genes, thereby controlling the disease resistance of poplars, which provides clues for understanding pto-miR159a role in coordinating poplar-pathogen interactions.