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1.
Gen Psychiatr ; 37(2): e101225, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38562407

RESUMEN

Background: The co-occurrence of depression and anxiety among adolescents is typically associated with suicide ideation. Aims: The study aimed to investigate the symptom-level relationship between suicide ideation and the comorbidity of depression and anxiety. Methods: 1501 adolescents aged 12-19 years were assessed using the Patient Health Questionnaire (PHQ-9) and the Generalized Anxiety Disorder Scale, and 716 adolescents who scored ≥5 on both scales were selected as participants. Network analysis was used to identify the network structure of depressive symptoms and anxiety symptoms. Participants were categorised into either the suicide ideation or non-suicide ideation groups based on their scoring on the suicide-related item in PHQ-9. A comparison was made between the depression-anxiety symptom networks of the two groups. Results: 'Restlessness', 'sad mood' and 'trouble relaxing' were the most prominent central symptoms in the depression-anxiety symptom network, and 'restlessness', 'nervousness' and 'reduced movement' were the bridge symptoms in this network. 'Sad mood' was found to be directly related to 'suicide ideation' with the highest variance. The network structure was significantly different in properties between the suicide ideation group and the non-suicide ideation group, with 'restlessness' and 'sad mood' exhibiting significantly higher influence in the network of the suicide ideation group than that in the non-suicide ideation group. Conclusion: Restlessness and sad mood could be targeted for the intervention of depression-anxiety symptoms among adolescents with suicide ideation.

2.
Environ Res ; 251(Pt 1): 118389, 2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38460661

RESUMEN

Phytoremediation has emerged as a common technique for remediating Cd pollution in farmland soil. Moreover, phosphorus, an essential element for plants, can alter the pectin content of plant cell walls and facilitate the accumulation of Cd in plant tissues, thereby enhancing phytoremediation efficiency. Therefore, pot experiments were conducted in order to investigate the effect of phosphorus levels on Cd extraction, phosphorus transformation and phosphorus-related genes during phytoremediation. The results revealed that an optimal application of suitable phosphate fertilizers elevated the soil's pH and electrical conductivity (EC), facilitated the conversion of soil from insoluble phosphorus into available forms, augmented the release of pertinent enzyme activity, and induced the expression of phosphorus cycling-related genes. These enhancements in soil conditions significantly promoted the growth of ryegrass. When applying phosphorus at a rate of 600 mg/kg, ryegrass exhibited plant height, dry weight, and chlorophyll relative content that were 1.27, 1.26, and 1.18 times higher than those in the control group (P0), while the Cd content was 1.12 times greater than that of P0. The potentially toxic elements decline ratio and bioconcentration factor were 42.86% and 1.17 times higher than those of P0, respectively. Consequently, ryegrass demonstrated the highest Cd removal efficiency under these conditions. Results from redundancy analysis (RDA) revealed a significant correlation among pH, total phosphorus, heavy metal content, phosphorus forms, soil enzyme activity, and phosphorus-related genes. In conclusion, this study suggests applying an optimal amount of suitable phosphate fertilizers can enhance restoration efficiency, leading to a reduction in soil Cd content and ultimately improving the safety of crop production in farmlands.

3.
Water Res ; 250: 121024, 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38113597

RESUMEN

Benzethonium chloride (BZC) is viewed as a promising disinfectant and widely applied in daily life. While studies related to its effect on waste activated sludge (WAS) anaerobic fermentation (AF) were seldom mentioned before. To understand how BZC affects AF of WAS, production of short chain fatty acids (SCFAs), characteristics of WAS as well as microbial community were evaluated during AF. Results manifested a dose-specific relationship of dosages between BZC and SCFAs and the optimum yield arrived at 2441.01 mg COD/L with the addition of 0.030 g/g TSS BZC. Spectral results and protein secondary structure variation indicated that BZC denatured proteins in the solid phase into smaller proteins or amino acids with unstable structures. It was also found that BZC could stimulate the extracellular polymeric substances secretion and reduce the surface tension of WAS, leading to the enhancement of solubilization. Beside, BZC promoted the hydrolysis stage (increased by 7.09 % to 0.030 g/g TSS BZC), but inhibited acetogenesis and methanogenesis stages (decreased by 6.85 % and 14.75 % to 0.030 g/g TSS BZC). The microbial community was also regulated by BZC to facilitate the enrichment of hydrolytic and acidizing microorganisms (i.e. Firmicutes). All these variations caused by BZC were conducive to the accumulation of SCFAs. The findings contributed to investigating the effect of BZC on AF of WAS and provided a new idea for the future study of AF mechanism.


Asunto(s)
Bencetonio , Aguas del Alcantarillado , Fermentación , Anaerobiosis , Aguas del Alcantarillado/química , Ácidos Grasos Volátiles , Concentración de Iones de Hidrógeno
4.
Sci Total Environ ; 900: 165774, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37499831

RESUMEN

A variety of variables limit the recovery of resources from anaerobic fermentation of waste activated sludge (WAS), hence pretreatment strategies are necessary to be investigated to increase its efficiency. A combination of free nitrous acid (FNA) and calcium hypochlorite [Ca(ClO)2] was employed in this investigation to significantly improve sludge fermentation performance. The yields of cumulative hydrogen for the blank and FNA treatment group were 1.09 ± 0.16 and 7.36 ± 0.21 mL/g VSS, respectively, and 6.59 ± 0.24 [0.03 g Ca(ClO)2/g TSS], 7.75 ± 0.20 (0.06), and 8.58 ± 0.22 (0.09) mL/g VSS for the Ca(ClO)2 groups. The co-treatment greatly boosted hydrogen generation, ranging from 39.97 ± 2.26 to 76.20 ± 4.78 % as compared to the solo treatment. Mechanism analysis demonstrated that the combined treatment disturbed sludge structure and cell membrane permeability even more, which released more organic substrates and enhanced biodegradability of fermentation broth. This paper describes a unique strategy to sludge pretreatment that expands the use of Ca(ClO)2 and FNA in anaerobic fermentation, with implications for sludge disposal and energy recovery.


Asunto(s)
Ácido Nitroso , Aguas del Alcantarillado , Aguas del Alcantarillado/química , Ácido Nitroso/análisis , Ácidos Grasos Volátiles/análisis , Fermentación , Hidrógeno/análisis , Anaerobiosis
5.
Cell Chem Biol ; 30(10): 1248-1260.e4, 2023 10 19.
Artículo en Inglés | MEDLINE | ID: mdl-37442135

RESUMEN

Speckle-type pox virus and zinc finger (POZ) protein (SPOP), a substrate recognition adaptor of cullin-3 (CUL3)/RING-type E3 ligase complex, is investigated for its role in cardiac fibrosis in our study. Cardiac fibroblasts (CFs) activation was achieved with TGF-ß1 (20 ng/mL) and MI mouse model was established by ligation of the left anterior descending coronary, and lentivirus was employed to mediate interference of SPOP expression. SPOP was increased both in fibrotic post-MI mouse hearts and TGF-ß1-treated CFs. The gain-of-function of SPOP promoted myofibroblast transformation in CFs, and exacerbated cardiac fibrosis and cardiac dysfunction in MI mice, while the loss-of-function of SPOP exhibited the opposite effects. Mechanistically, SPOP bound to the receptor of activated protein C kinase 1 (RACK1) and induced its ubiquitination and degradation by recognizing Ser/Thr-rich motifs on RACK1, leading to Smad3-mediated activation of CFs. Forced RACK1 expression canceled the effects of SPOP on cardiac fibrosis. The study reveals therapeutic targets for fibrosis-related cardiac diseases.


Asunto(s)
Infarto del Miocardio , Factor de Crecimiento Transformador beta1 , Animales , Ratones , Fibrosis , Infarto del Miocardio/complicaciones , Infarto del Miocardio/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Receptores de Cinasa C Activada , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/farmacología
6.
Alcohol Clin Exp Res (Hoboken) ; 47(7): 1377-1389, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-37428421

RESUMEN

BACKGROUND: Worldwide, alcohol use is a major contributor to the burden of disease and mortality. A sizeable literature suggests that brief web-based interventions that incorporate personalized normative and/or health consequences feedback are effective at reducing alcohol intake. The relative efficacy of an intervention that also includes individualized feedback about brain health has not been examined, nor has the utility of integrating a smartphone app component. METHOD: Participants (N = 436, Mage = 21.27) completed baseline protocols (n = 178 recorded alcohol use via an app for 14 days) and were then assigned to one of three feedback conditions using randomized block allocation with stratification based on the total number of standard drinks consumed. Control participants received no feedback; Alcohol Intake Feedback (Alc) participants received personalized information about their alcohol use; Alcohol Intake plus Cognitive Feedback (AlcCog) participants received personalized details about alcohol use plus individualized brain-health information related to impulsivity. The impact of feedback on alcohol consumption behavior was examined as a function of feedback condition and hazardous/non-harmful drinking status (as defined by the World Health Organization) at an 8-week follow-up. RESULTS: Hazardous drinkers in both the Alc and AlcCog conditions reduced their alcohol intake by 31% to 50% more than those in the Control condition. Reductions were not related to whether participants completed web- plus app-based components or web-only components of the intervention. There was no change in the alcohol intake of non-harmful drinkers. CONCLUSIONS: This proof-of-concept study showed that hazardous drinkers respond well to brief electronic interventions that incorporate personalized normative and/or health consequences feedback. Further research is required to determine how best to make impulsivity-related brain-health consequences of drinking manifest and how to maximize the potential of smartphones apps.

7.
Sci Total Environ ; 894: 164966, 2023 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-37343852

RESUMEN

Insufficient absorption sites and low charge separation notably limit the activation of photocatalytic molecular oxygen. In this study, atomic-layer BiOBr (BiOBr-QDs)/ZnAl-LDH composites with a considerable number of edges were developed to address the above-mentioned problems. The result of this study indicated the spatial separation of atomic-layer BiOBr-QDs/ZnAl-LDH's conduction band maximum (CBM) and valence band minimum (VBM). As a result, holes were produced on the substrate surface based on irradiation, and electrons were generated at the sites of the edge, such that ultra-fast charge separation can be carried out. The edges exposed massive adsorption sites in terms of oxygen molecules. Thus, electrons at the sites of the edge led to the reduction of absorbed oxygen molecules, thus exhibiting stronger photocatalytic •O2- production. Furthermore, the result confirmed that the atomic layer BiOBr-QDs/ZnAl-LDH are promising in environmental catalytic degradation for its increased activity of •O2- production. In this study, a novel insight into advanced photocatalyst design based on edge unsaturated ligand engineering at an atomic level is provided.

8.
Chemosphere ; 332: 138906, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37169090

RESUMEN

ABO3-type perovskite oxides have been regarded as a kind of potential catalyst for peroxymonosulfate (PMS) activation. But some limitations such as specific pH conditions and coexisting ion interference restrict its practical application. Herein, a lanthanum copper Ruddlesden-Popper perovskite oxide (La2CuO4) was successfully synthesized through the sol-gel process and applied in the activation of PMS. And for the first time the La2CuO4/PMS system was used for tetracycline hydrochloride (TC-HCl) degradation. Results showed that La2CuO4 was a potential PMS activation catalyst in the removal of antibiotics. At optimized condition (0.2 g/L catalysts, 1 mM PMS, pH0 6.9), 96.05% of TC-HCl was removed in 30 min. In experiments of debugging control conditions, over a wide pH range of 3-11, more than 90% of TC-HCl can be removed. In the natural water treatment process, TC-HCl removal rates of about 84.2% and 70.3% were obtained in tap water and River water, respectively. According to the reusability and stability tests and the results of FTIR and XPS analysis, La2CuO4 had high structural and chemical stability. Electron paramagnetic resonance (EPR) suggested that the active species including ·OH, SO4-· and 1O2 were detected in degradation reaction. Finally, reasonable reaction mechanisms and possible degradation pathways of TC-HCl were proposed. These results indicate that La2CuO4 can act as a potential catalyst for PMS activation to degrade TC-HCl in water.


Asunto(s)
Cobre , Tetraciclina , Lantano , Óxidos , Peróxidos/química
9.
Bioresour Technol ; 373: 128754, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36801444

RESUMEN

Numerous effective chemical strategies have been explored for short-chain fatty acids (SCFAs) production from waste activated sludge (WAS), but many technologies have been questioned due to the chemical residues. This study proposed a citric acid (CA) treatment strategy for improving SCFAs production from WAS. The optimum SCFAs yield reached 384.4 mg COD/g VSS with 0.08 g CA/g TSS addition. Meanwhile, CA biodegradation occurred and its contribution to the yield of total SCFAs, especially acetic acid, cannot be ignored. Intensive exploration indicated the sludge decomposition, the biodegradability of fermentation substrates, as well as the abundance of fermenting microorganisms were definitely enhanced in the existence of CA. The optimization of SCFAs production techniques based on this study deserved further study. This study comprehensively revealed the performance and mechanisms of CA enhancing biotransformation of WAS into SCFAs and the findings promotes the research of carbon resource recovery from sludge.


Asunto(s)
Ácidos Grasos Volátiles , Aguas del Alcantarillado , Aguas del Alcantarillado/química , Fermentación , Ácido Acético , Biotransformación , Concentración de Iones de Hidrógeno
10.
FASEB J ; 37(3): e22797, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36753405

RESUMEN

Cardiac fibrosis is a common pathological manifestation in multiple cardiovascular diseases and often results in myocardial stiffness and cardiac dysfunctions. LncRNA (long noncoding RNA) participates in a number of pathophysiological processes. However, its role in cardiac fibrosis remains unclear. The purpose of this study was to investigate the role and molecular mechanism of MetBil in regulating cardiac fibrosis. Our data showed that METTL3 binding lncRNA (MetBil) was significantly increased both in fibrotic tissue following myocardial infarction (MI) in mice and in cardiac fibroblasts (CFs) exposed to TGF-ß1 (20 ng/mL) or 20% FBS. Overexpression of MetBil augmented collagen deposition, CF proliferation and activation while silencing MetBil exhibited the opposite effects. Importantly, heterozygous knockout of MetBil alleviated cardiac fibrosis and improved cardiac function after MI. RNA pull-down and RNA-binding protein immunoprecipitation assay showed that METTL3 is a direct downstream target of MetBil; consistently, MetBil and METTL3 were co-localized in both the nucleus and cytoplasm of CFs. Interestingly, MetBil regulated METTL3 expression at protein level, but not mRNA level, in ubiquitin-proteasome pathway. Enforced expression of METTL3 canceled the antifibrotic effects of silencing MetBil reflected by increased collagen production, CF proliferation and activation. Most notably, the m6A-modified fibrosis-regulated genes mediated by METTL3 are profoundly involved in the regulation of MetBil in the cardiac fibrosis following MI. Our study reveals that MetBil as a novel regulator of fibrosis promotes cardiac fibrosis via interacting with METTL3 and regulating the expression of the methylated fibrosis-associated genes, providing a new intervening target for fibrosis-associated cardiac diseases.


Asunto(s)
Cardiopatías , Infarto del Miocardio , ARN Largo no Codificante , Ratones , Animales , ARN Largo no Codificante/genética , Infarto del Miocardio/metabolismo , Fibrosis , Metiltransferasas/genética , Metiltransferasas/metabolismo , Colágeno/genética , Colágeno/metabolismo
11.
J Environ Manage ; 335: 117540, 2023 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-36841004

RESUMEN

Iron and manganese oxides/biochar composite materials (Fe/Mn-BC) are promising catalysts in the field of advanced oxidation. High purity chemical reagents are popular precursors for preparing Fe/Mn-BC, while the potential of low-cost natural minerals as precursors has been neglected. In this study, high-efficiency Fe/Mn-BC was synthesized by one-step pyrolysis method using hematite, phosphoromanganese, and bagasse. The synthesized Fe/Mn-BC removed 83.7% 2, 4-dichlorophenol (2, 4-DCP) within 30 min, about 8.8 and 10.6 times better than biochar (BC) and Fe/Mn complex, respectively. The removal of 2, 4-DCP in the Fe/Mn-BC + peroxydisulfate (PDS) system was influenced by catalyst dosage, PDS concentration, initial pH, organic acids, and chromium. Sulfate radical (SO4•-) and hydroxyl radicals (•OH) generated by Fe/Mn-BC-activated PDS have similar contribution to the degradation of 2,4-DCP. A possible removal mechanism of 2, 4-DCP in the Fe/Mn-BC + PDS system was proposed based on Electron Spin Resonance spectroscopy, free radical quenching experiments, X-ray photoelectron spectroscopy, X-ray diffraction, and electrochemical measurement. Fe0 and Fe(II) in Fe/Mn-BC play significant role in catalytic degradation of 2, 4-DCP at the early stage of the reaction (within 0-5 min). Then, the interaction between Mn and BC or structural Mn and structural Fe gradually became dominant in the later stage. Similarly, the electron transfer promoted by biochar also played an important role in this catalysis. This discovery provided a new strategy for developing iron and manganese oxides/biochar composite materials to activate PDS for the elimination of refractory organic pollutants.


Asunto(s)
Aguas Residuales , Contaminantes Químicos del Agua , Manganeso/química , Carbón Orgánico/química , Óxidos/química , Hierro/química , Minerales , Fenoles , Oxidación-Reducción , Catálisis , Contaminantes Químicos del Agua/química
12.
Gene Ther ; 30(1-2): 142-149, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35644811

RESUMEN

Dystrophin deficiency due to genetic mutations causes cardiac abnormalities in Duchenne's muscular dystrophy. Dystrophin is also shown to be downregulated in conventional failing hearts. Whether restoration of dystrophin expression possesses any therapeutic potential for conventional heart failure (HF) remains to be examined. HF mouse model was generated by transverse aortic constriction (TAC). In vivo activation of dystrophin transcription was achieved by tail-vein injection of adeno-associated virus 9 carrying CRISPR/dCas system for dystrophin. We found that activation of dystrophin expression in TAC mice significantly reduced the susceptibility to arrhythmia of TAC mice and the mortality rate. We further demonstrated that over-expression of dystrophin increased cardiac conduction of hearts in TAC mice by optical mapping evaluation. Activation of dystrophin expression also increased peak sodium current in isolated ventricular myocytes from hearts of TAC mice as recorded by the patch-clamp technique. Immunoblotting and immunofluorescence showed that increased dystrophin transcription restored the membrane distribution of Nav1.5 in the hearts of TAC mice. In summary, correction of dystrophin downregulation by the CRISPR-dCas9 system reduced the susceptibility to arrhythmia of conventional HF mice through restoring Nav1.5 membrane distribution. This study paved the way to develop a new therapeutic strategy for HF-related ventricular arrhythmia.


Asunto(s)
Insuficiencia Cardíaca , Distrofia Muscular de Duchenne , Ratones , Animales , Distrofina/genética , Distrofina/metabolismo , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas , Arritmias Cardíacas/genética , Arritmias Cardíacas/terapia , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia
13.
RSC Adv ; 12(22): 14175-14182, 2022 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-35558833

RESUMEN

Highly crystalline glass-ceramics were successfully manufactured via a one-step direct cooling method using Shuangqishan (Fujian, China) gold tailings as raw materials. A series of glass-ceramics were prepared by controlling the gold tailings addition and post-treatment. X-ray diffraction results show that the crystalline phase of glass-ceramics samples with high tailing addition content (65-80 wt%) is akermanite phase (Ca2MgSi2O7). By contrast, the main phase of 60 wt% and 55 wt% tailings addition samples is diopside (CaMgSi2O6) crystalline phase. In addition, although glass-ceramics have typical fracture characteristics of brittle materials, the crack propagation in the fracture process is disturbed by grains, resulting in the deviation of the fracture path in terms of macroscopic and microcosmic observation. Based on the investigation of samples with different tailings additions, glass-ceramics with 60 wt% tailings contents show excellent mechanical properties with a density of 2.89 g cm-3, a Vickers hardness value of 8.17 GPa, and a flexural strength of 116 MPa after 950 °C heat treatment. This study further confirms the possibility of using Shuangqi Mountain gold tailings as the raw materials for highly crystalline glass-ceramics, which shows great potential for application in mass production.

14.
Mol Genet Genomic Med ; 10(6): e1943, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35388601

RESUMEN

BACKGROUND: Mitochondrial disease (MD) is genetically a heterogeneous group of disorders with impairment in respiratory chain complexes or pathways associated with the mitochondrial function. Nowadays, it is still a challenge for the genetic screening of MD due to heteroplasmy of mitochondrial genome and the complex model of inheritance. This study was designed to investigate the feasibility of whole exome sequencing (WES)-based testing as an alternative option for the diagnosis of MD. METHODS: A Chinese Han cohort of 48 patients with suspect MD features was tested using nanoWES, which was a self-designed WES technique that covered the complete mtDNA genome and 21,019 nuclear genes. Fourteen patients were identified with a single genetic variant and three with single deletion in mtDNA. RESULTS: The heteroplasmy levels of variants in mitochondrial genome range from 11% to 100%. NanoWES failed to identify multiple deletions in mtDNA compared with long range PCR and massively parallel sequencing (LR-PCR/MPS). However, our testing showed obvious advantages in identifying variations in nuclear DNA. Based on nanoWES, we identified two patients with nuclear DNA variation. One of them showed Xp22.33-q28 duplication, which indicated a possibility of Klinefelter syndrome. CONCLUSION: NanoWES yielded a diagnostic rate of 35.4% for MD. With the rapid advances of next generation sequencing technique and decrease in cost, we recommend the usage of nanoWES as a first-line method in clinical diagnosis.


Asunto(s)
ADN Mitocondrial , Enfermedades Mitocondriales , ADN Mitocondrial/genética , Humanos , Mitocondrias/genética , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/genética , Análisis de Secuencia de ADN/métodos , Secuenciación del Exoma
15.
Sci Total Environ ; 822: 153483, 2022 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-35093361

RESUMEN

It has been confirmed that silicon (Si) fertilizer and humic acid (HA) could effectively decrease the heavy metals in soil. Nonetheless, the impact of these additives on soil aggregate characteristics was ignored. Therefore, the effects of Si fertilizer, HA, and their combinations on the physicochemical characteristics, availability of heavy metals (Cu, Cd, Pb, Zn), and fraction changes in soils and soil aggregates were investigated in this research. The results showed that Si fertilizer and HA significantly modified soil properties such as soil pH, electrical conductivity total organic carbon, water-soluble organic carbon, and nitrate­nitrogen. HA and Si-HA (SHA) supplementation significantly decreased the availability of Cu, Cd, Pd, and Zn. Besides, there was no significant difference in physicochemical properties between soil and soil aggregates. The availability of Cu, Cd, Pd, and Zn in soil aggregates could be significantly inhibited by the addition of HA and SHA, and the content in microaggregates was greater than that in macroaggregates. After the addition of the three additives, the main fractions of heavy metals in different particle sizes were changed and eventually transformed to the residue state. These results indicated that Si fertilizer, HA, and SHA were influential in physicochemical properties and metal availability in soil aggregates. Therefore, it is of great scientific significance to study the impact of heavy metal pollution on the ecological environment in different aggregates, which will provide reference data for future sustainable management of heavy-metal polluted soils.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , China , Fertilizantes/análisis , Sustancias Húmicas , Metales Pesados/análisis , Silicio , Suelo/química , Contaminantes del Suelo/análisis
16.
Sci China Life Sci ; 65(6): 1198-1212, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-34668131

RESUMEN

Diabetic cardiomyopathy (DCM) is a common complication in diabetic patients. The molecular mechanisms of DCM remain to be fully elucidated. The intronic long noncoding RNA of DACH1 (lncDACH1) has been demonstrated to be closely associated with heart failure and cardiac regeneration. In this study, we investigated the role of lncDACH1 in DCM and the underlying molecular mechanisms. The expression of lncDACH1 was increased in DCM hearts and in high glucose-treated cardiomyocytes. Knockout of lncDACH1 reduced mitochondrial oxidative stress, cell apoptosis, cardiac fibrosis and hypertrophy, and improved cardiac function in DCM mice. Overexpression of lncDACH1 exacerbated mitochondria-derived reactive oxygen species (ROS) level and apoptosis, decreased activity of manganese superoxide dismutase (Mn-SOD); while silencing of lncDACH1 attenuated ROS production, mitochondrial dysfunction, cell apoptosis, and increased the activity of Mn-SOD in cardiomyocytes treated with high glucose. LncDACH1 directly bound to sirtuin3 (SIRT3) and facilitated its degradation by ubiquitination, therefore promoting mitochondrial oxidative injury and cell apoptosis in mouse hearts. In addition, SIRT3 silencing abrogated the protective effects of lncDACH1 deficiency in cardiomyocytes. In summary, lncDACH1 aggravates DCM by promoting mitochondrial oxidative stress and cell apoptosis via increasing ubiquitination-mediated SIRT3 degradation in mouse hearts. Inhibition of lncDACH1 represents a novel therapeutic strategy for the intervention of diabetic cardiomyopathy.


Asunto(s)
Diabetes Mellitus , Cardiomiopatías Diabéticas , ARN Largo no Codificante , Sirtuina 3 , Animales , Apoptosis/genética , Diabetes Mellitus/metabolismo , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/metabolismo , Glucosa/farmacología , Humanos , Ratones , Ratones Noqueados , Miocitos Cardíacos/metabolismo , Estrés Oxidativo , ARN Largo no Codificante/genética , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 3/genética , Sirtuina 3/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo
17.
Front Pharmacol ; 12: 631835, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33664669

RESUMEN

Purpose: Cardiomyocyte senescence is associated with a progressive decline in cardiac physiological function and the risk of cardiovascular events. lncRNA H19 (H19), a well-known long noncoding RNA (lncRNA), is involved in the pathophysiological process of multiple cardiovascular disease such as heart failure, cardiac ischemia and fibrosis. However, the role of H19 in cardiomyocyte senescence remains to be further explored. Methods: Senescence-associated ß-galactosidases (SA-ß-gal) staining was used to detect cardiomyocyte senescence. Western blot, qRT-PCR and luciferase reporter assay were employed to evaluate the role of H19 in cardiomyocyte senescence and its underling molecular mechanism. Results: H19 level was significantly increased in high glucose-induced senescence cardiomyocytes and aged mouse hearts. Overexpression of H19 enhanced the number of SA-ß-gal-positive cells, and the expression of senescence-related proteins p53 and p21, whereas H19 knockdown exerted the opposite effects. Mechanistically, H19 was demonstrated as a competing endogenous RNA (ceRNA) for microRNA-19a (miR-19a): H19 overexpression downregulated miR-19a level, while H19 knockdown upregulated miR-19a. The expression of SOSC1 was dramatically increased in senescence cardiomyocytes and aged mouse hearts. Further experiments identified SOCS1 as a downstream target of miR-19a. H19 upregulated SOCS1 expression and activated the p53/p21 pathway by targeting miR-19a, thus promoting the cardiomyocytes senescence. Conclusion: Our results show that H19 is a pro-senescence lncRNA in cardiomyocytes acting as a ceRNA to target the miR-19a/SOCS1/p53/p21 pathway. Our research reveals a molecular mechanism of cardiomyocyte senescence regulation and provides a novel target of the therapy for senescence-associated cardiac diseases.

18.
Braz. j. pharm. sci ; 51(3): 673-679, July-Sept. 2015. tab
Artículo en Inglés | LILACS | ID: lil-766325

RESUMEN

This work aims to study the pathogenesis of learning and memory impairment in offspring rats resulting from maternal enflurane anesthesia by focusing on the expression of the N-methyl-d-aspartic acid receptor subunit 2B (NR2B) in the hippocampus of the offspring. Thirty female Sprague-Dawley rats were randomly divided into three groups: control (C group), 4 h enflurane exposure (E1 group), and 8 h enflurane exposure (E2 group) groups. Eight to ten days after the initiation of pregnancy, rats from the E1 and E2 groups were allowed to inhale 1.7% enflurane in 2 L/min oxygen for 4 h and 8 h, respectively. Rats from the C group were allowed to inhale 2 L/min of oxygen only. The Morris water maze was used to assay the learning and memory function of the offspring on postnatal days 20 and 30. RT-PCR and immunohistochemistry assays were then used to measure the mRNA levels and protein expression of NR2B, respectively. Relative to offspring rats from the C group, those from the E1 and E2 groups exhibited longer escape latencies, lesser number of crossings over the platform, and less time spent in the target quadrant in the spatial exploration test (P < 0.05). In addition, the mRNA and protein expression levels of NR2B in the hippocampus of offspring rats in the E1 and E2 groups were down-regulated (P < 0.05). No significant differences between the E1 and E2 groups were observed (P > 0.05) in terms of mRNA levels and protein expression of NR2B. The cognitive function of the offspring is impaired when maternal rats are exposed to enflurane during early pregnancy. A possible mechanism of this effect is related to the down-regulation of NR2B expression.


Este trabalho objetiva o estudo da patogênese de deficiência no aprendizado e memória de prole de ratos resultante da anestesia maternal por enflurano, por meio da expressão da subunidade 2B do receptor do ácidoN-metil-D-aspártico (NR2B) no hipocampo dos filhotes. Dividiram-se, aleatoriamente, 30 fêmeas de ratos Sprague-Dawley em três grupos: controle (grupo C), exposição ao enflurano por 4 h (grupo E1) e por 8 h (grupo E2). De oito a 10 dias após o início da gravidez, os ratos dos grupos E1 e E2 inalaram enflurano 1,7% em 2 L/min de oxigênio, por 4 h e 8 h, respectivamente. Ratos do grupo C inalaram apenas 2 L/min de oxigênio. O labirinto de água de Morris foi empregado para analisar as funções de aprendizado e memória da cria em 20 e 30 dias após o nascimento. Utilizaram-se ensaios de RT-PCR e de imuno-histoquímica para medir os níveis de mRNA e expressão da proteína do NR2B, respectivamente. Em comparação com os ratos controle do grupo C, aqueles dos grupos E1 e E2 exibiram latências de escape mais longas, menor número de travessias na plataforma e menos tempo gasto no quadrante alvo no teste de exploração espacial (P < 0,05). Adicionalmente, os níveis de expressão de mRNA e de proteína do NR2B no hipocampo dos filhotes nos grupos E1 e E2 estavam reduzidos (P < 0,05). Não se observaram diferenças significativas entre os grupos E1 e E2 (P < 0,05) quanto aos níveis de mRNA e à expressão de proteína de NR2B. A função cognitiva dos filhotes é prejudicada quando as mães são expostas ao enflurano durante o início da gravidez. O mecanismo possível para esse efeito está relacionado à diminuição na expressão de NR2B.


Asunto(s)
Ratas , Embarazo , Exposición Materna/clasificación , Enflurano/análisis , Expresión Génica/inmunología , N-Metilaspartato/análisis , Anestesia
19.
J Phys Chem B ; 112(42): 13273-84, 2008 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-18826266

RESUMEN

Classical molecular dynamics (MD) simulations were performed to determine the hydrated morphology and hydronium ion diffusion coefficients in two different perfluorosulfonic acid (PFSA) membranes as functions of water content. The structural and transport properties of 1143 equivalent weight (EW) Nafion, with its relatively long perfluoroether side chains, are compared to the short-side-chain (SSC) PFSA ionomer at an EW of 977. The separation of the side chains was kept uniform in both ionomers consisting of -(CF 2) 15- units in the backbone, and the degree of hydration was varied from 5 to 20 weight % water. The MD simulations indicated that the distribution of water clusters is more dispersed in the SSC ionomer, which leads to a more connected water-channel network at the low water contents. This suggests that the SSC ionomer may be more inclined to form sample-spanning aqueous domains through which transport of water and protons may occur. The diffusion coefficients for both hydronium ions and water molecules were calculated at hydration levels of 4.4, 6.4, 9.6, and 12.8 H 2O/SO 3H for each ionomer. When compared to experimental proton diffusion coefficients, this suggests that as the water content is increased the contribution of proton hopping to the overall proton diffusion increases.

20.
J Phys Chem B ; 111(9): 2208-18, 2007 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-17288476

RESUMEN

A molecular dynamics simulation study of hydrated Nafion at water contents ranging from 5 to 20 wt % was performed to examine the structure and dynamics of the hydrated polyelectrolyte system. The simulations show that the system forms segregated hydrophobic regions consisting primarily of the polymer backbone and hydrophilic regions with an inhomogeneous water distribution. We find that the water clustering strongly depends on the water content. At low water content, only isolated small water clusters are formed. As the water content increases, it becomes increasingly possible that a predominant majority of water molecules form a single cluster, suggesting that the hydrophilic regions become connected. We characterize the atomic structures formed within the system by various atomic pair correlation functions. The water structure factor shows a peak at q values corresponding to an intercluster distance about 2.5 nm and greater. With increasing water content, the distance moves to larger values, consistent with findings from scattering experiments. We find that the degree of solvation of hydronium ions by water molecules is a strong function of water content. At 5 wt %, a majority of the hydronium ions are hydrated by no more than two water molecules, prohibiting structural diffusion. As water content increases, the hydronium ions continue to become increasingly hydrated, resulting in structures capable of forming eigen ions, a necessary step in structural diffusion. Addressing the experimentally observed fact that conductivity in these membranes abruptly drops near 5 wt %, we find that both the local structure of the poorly hydrated hydronium ions and the disconnected nature of the global morphology of the water nanonetwork at low water content should contribute to poor conductivity.

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