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2.
Life Sci ; 328: 121873, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37352916

RESUMEN

Heart failure typically occurs early in the clinical course of sustained cardiac hypertrophy that is accompanied by maladaptive remodeling of the heart. It is critical to discover new mechanisms and effective therapeutic targets to prevent and cure pathological cardiac hypertrophy. The objective of the study was to evaluate the effects of circRNAs on NSD2-induced ventricular remodeling. We screened the dysregulated circRNAs in normal or NSD2-/- C57BL/6 mice with or without transverse aortic constriction (TAC), and found that circCmss1 significantly increased in normal TAC mice, but decreased in NSD2-/- TAC mice. Angiotensin II(Ang II)induced neonatal cardiomyocyte hypertrophy in vitro and the pressure overload-induced cardiac hypertrophy in vivo can be reduced by Knocking down circCmss1. We further investigated the downstream signaling of circCmss1 in the progression of NSD2-promoted ventricular remodeling and discovered that circCmss1 could interact with a transcription factor EIF4A3 and induce the expression of transferrin receptor 1 (TfR1), thus activating the ferroptosis in cardiomyocytes. This study highlights the significance of NSD2 activation of circCmss1/EIF4A3/TfR1 as therapeutic targets for treating pathological myocardial hypertrophy.


Asunto(s)
Ferroptosis , Remodelación Ventricular , Animales , Ratones , Cardiomegalia/metabolismo , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , ARN Circular/metabolismo
3.
Front Cell Neurosci ; 17: 1276506, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38188669

RESUMEN

Accaumulating studies focus on the effects of C3-positive A1-like phenotypes and S100A10-positive A2-like phenotypes of reactive astrocytes on spinal cord injury (SCI), however the origins and dynamic changes of C3- and S100A10-positive reactive astrocytes after SCI remain poorly understood. Through transgenic mice and lineage tracing, we aimed to determine the origins of C3- and S100A10-positive reactive astrocytes. Meanwhile, the distribution and dynamic changes in C3- and S100A10-positive reactive astrocytes were also detected in juvenile and adult SCI mice models and cultured astrocytes. Combing with bulk RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq) and bioinformatic analysis, we further explored the dynamic transcripts changes of C3- and S100A10-positive reactive astrocytes after SCI. We confirmed that resident astrocytes produced both C3- and S100A10-positive reactive astrocytes, whereas ependymal cells regenerated only S100A10-positive reactive astrocytes in lesion area. Importantly, C3-positive reactive astrocytes were predominantly activated in adult SCI mice, while S100A10-positive reactive astrocytes were hyperactivated in juvenile mice. Furthermore, we observed that C3- and S100A10-positive reactive astrocytes had a dynamic transformation process at different time in vitro and vivo, and a majority of intermediate states of C3- and S100A10-positive reactive astrocytes were found during transformation. RNA-seq and scRNA-seq results further confirmed that the transcripts of C3-positive reactive astrocytes and their lipid toxicity were gradually increased with time and age. In contrast, S100A10-positive reactive astrocytes transcripts increased at early time and then gradually decreased after SCI. Our results provide insight into the origins and dynamic changes of C3- and S100A10-positive reactive astrocytes after SCI, which would be valuable resources to further target C3- and S100A10-positive reactive astrocytes after SCI.

4.
Antioxidants (Basel) ; 11(10)2022 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-36290704

RESUMEN

The imbalance between pro-oxidants and antioxidants is thought to be responsible for aging and cognitive impairment in many degenerative diseases, including schizophrenia (SZ). As the first antioxidant enzyme to detoxify superoxide radicals in mitochondria, manganese superoxide dismutase (MnSOD) activity and its functional polymorphism of Ala-9Val have been found to be associated with SZ. In this study, we explored the association between MnSOD activity, MnSOD Ala-9Val polymorphism and cognitive dysfunction in unmedicated first-episode (UMFE) SZ patients, which has not been examined. We recruited 234 UMFE SZ patients and 232 healthy controls (HC) and evaluated them with Repeated Battery for the Assessment of Neuropsychological Status (RBANS), plasma MnSOD activity and MnSOD Ala-9Val (rs4880) polymorphism. In addition, we used the Positive and Negative Syndrome Scale (PANSS) to assess the severity of patients' psychopathological symptoms. Compared with HC, UMFE patients showed extensive cognitive impairment on RBANS, and had higher MnSOD activity. MnSOD Ala-9Val polymorphism was not associated with SZ susceptibility and cognitive impairment, but only affected MnSOD activity in patients. Moreover, only in SZ patients with Val homozygotes, MnSOD activity was significantly correlated with cognitive impairment, especially in RBANS total score, visuospatial/constructional and attention index scores. Our results suggest that cognitive impairment is associated with MnSOD activity in patients with first-episode SZ, which may be regulated by MnSOD Ala-9Val polymorphism.

5.
Front Endocrinol (Lausanne) ; 13: 880683, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35651978

RESUMEN

Objectives: Non-alcoholic fatty liver disease (NAFLD) greatly affects cardiovascular disease, but evidence on the associations between NAFLD and markers of aortic calcification is limited. We aim to evaluate the association between NAFLD and aortic calcification in a cohort of Chinese adults using propensity score-matching (PSM) analysis. Methods: This prospective cohort study involved adults who underwent health-screening examinations from 2009 to 2016. NAFLD was diagnosed by abdominal ultrasonography at baseline, and aortic calcification was identified using a VCT LightSpeed 64 scanner. Analyses included Cox proportional-hazards regression analysis and PSM with predefined covariates (age, gender, marital and smoking status, and use of lipid-lowering drugs) to achieve a 1:1 balanced cohort. Results: Of the 6,047 eligible participants, 2,729 (45.13%) were diagnosed with NAFLD at baseline, with a median age of 49.0 years [interquartile range, 44.0-55.0]. We selected 2,339 pairs of participants with and without NAFLD at baseline for the PSM subpopulation. Compared with those without NAFLD, patients with NAFLD were at a higher risk of developing aortic calcification during follow-up; significant results were observed before and after matching, with the full-adjusted hazard ratios and corresponding 95% confidence intervals being 1.19 (1.02-1.38) and 1.18 (1.01-1.38), respectively (both p < 0.05). In subgroup analyses, no interaction was detected according to age, gender, smoking status, body mass index, total cholesterol, low-density lipoprotein cholesterol, use of lipid-lowering drugs, hypertension, or type 2 diabetes. Conclusions: NAFLD may be independently associated with aortic calcification. Further studies are warranted to elucidate the possible underlying mechanisms.


Asunto(s)
Diabetes Mellitus Tipo 2 , Enfermedad del Hígado Graso no Alcohólico , Adulto , Colesterol , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Lípidos , Persona de Mediana Edad , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Puntaje de Propensión , Estudios Prospectivos
6.
ACS Omega ; 7(12): 10187-10195, 2022 Mar 29.
Artículo en Inglés | MEDLINE | ID: mdl-35382326

RESUMEN

Under the hydrothermal condition, a new type of two-dimensional coordination polymer ([Cd(D-Cam)(3-bpdb)]n, Cd-CP) has been constructed. It is composed of D-(+)-Camphoric-Cd(II) (D-cam-Cd(II)) one-dimensional chain and bridging 1,4-bis(3-pyridyl)-2,3-diaza-1,3-butadiene (3-bpdb) ligands. Cd-CP has a good removal effect for Hg(II) and Pb(II), and the maximum adsorption capacity is 545 and 450 mg/g, respectively. Interestingly, thermodynamic studies have shown that the adsorption processes of Hg(II) and Pb(II) on Cd-CP use completely different thermodynamic mechanisms, in which the adsorption of Hg(II) is due to a strong electrostatic interaction with Cd-CP, while that of Pb(II) is through a weak coordination with Cd-CP. Moreover, Cd-CP has a higher affinity for Hg(II), and when Hg(II) and Pb(II) coexist, Cd-CP preferentially adsorbs Hg(II).

7.
Int J Biol Sci ; 18(4): 1651-1662, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35280686

RESUMEN

Myocardial ischemia/reperfusion (I/R) injury is recognized as the leading cause of death worldwide. However, the molecular mechanisms involved in this process are still not fully understood. We previously reported that the combined action of Notch1 and Keap1-NRF2 signaling pathway can significantly increase the activity of cardiomyocytes, inhibit the apoptosis of cardiomyocytes, reduce the formation of reactive oxygen species, and improve the antioxidant activity in neonate rat myocardial cells. However, the regulatory mechanism of Notch1 signaling pathway on the NRF2 signaling pathway and its actual role on I/R injury are still unclear. Herein, we found that Keap-NRF2 signaling is activated by Notch1 in RBP-Jκ dependent manner, thus protects the heart against I/R injury via inhibiting the mitochondrial ROS generation and improves the mitochondrial bioenergetics in vitro and in vivo. These results suggest that Keap-NRF2 signaling might become a promising therapeutic strategy for treating myocardial I/R injury.


Asunto(s)
Daño por Reperfusión Miocárdica , Daño por Reperfusión , Animales , Apoptosis/genética , Metabolismo Energético , Proteína 1 Asociada A ECH Tipo Kelch/genética , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Miocitos Cardíacos/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Receptor Notch1/genética , Receptor Notch1/metabolismo , Daño por Reperfusión/metabolismo , Transducción de Señal
8.
J Hazard Mater ; 427: 127852, 2022 04 05.
Artículo en Inglés | MEDLINE | ID: mdl-34838355

RESUMEN

The design and development of materials with a selective adsorption capacity for Pb(II) are very important for environmental governance and ecological safety. In this work, a novel 3D metal-organic framework ([Cd2H4L4Cl2SO4]·4H2O, Cd-MOF) is constructed using a multiple pyrazole heterocycles tetraphenylethylene-based ligand (H4L4) and CdSO4 which containing Pb(II) adsorption sites (SO42-). Studies have shown that the Cd-MOF has outstanding stability, and its maximum adsorption value of Pb(II) can be as high as 845.55 mg/g, which is higher than that of most MOFs or MOFs modified materials. It is worth emphasizing that the Cd-MOF have excellent recyclability due to the unique adsorption mechanism of the Cd-MOF. Thermodynamic studies have shown that Pb(II) adsorption of the Cd-MOF is a spontaneous endothermic process. Specific selective adsorption, exceptional stability and remarkable recyclability make the Cd-MOF a potential material for industrial capture and recovery of Pb(II) from water.


Asunto(s)
Estructuras Metalorgánicas , Contaminantes Químicos del Agua , Adsorción , Conservación de los Recursos Naturales , Política Ambiental , Plomo , Contaminantes Químicos del Agua/análisis
9.
World J Biol Psychiatry ; 23(7): 517-524, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-34918615

RESUMEN

Objectives: Cognitive decline is an essential characteristic of schizophrenia and may be due to the disturbance between reactive oxygen species generation and antioxidant capacity. The study aimed to explore the association between cognitive deficits and antioxidant defence parameters in untreated first-episode patients with schizophrenia.Methods: We determined important antioxidant enzymes, total superoxide dismutase (SOD) and manganese SOD (MnSOD), and their relationship with cognitive impairment in 168 untreated patients with first-episode schizophrenia and 168 age- and sex-matched healthy controls. The evaluation of psychopathological symptoms of all patients was based on the Positive and Negative Syndrome Scale (PANSS). We measured cognitive function by the Repeated Battery for the Assessment of Neuropsychological Status (RBANS) and activities of total SOD and MnSOD in all participants.Results: The results showed that untreated patients with first-episode schizophrenia had deficient cognitive functioning in four RBANS indices and total scores, except for the visuospatial/constructional index, as well as higher plasma total SOD activity compared with the control subjects. In addition, significant negative correlations were identified between MnSOD activity and attention index or RBANS total score in patients.Conclusions: Our results suggest that oxidative stress may be partly responsible for cognitive dysfunction in the early course of schizophrenia.


Asunto(s)
Disfunción Cognitiva , Esquizofrenia , Humanos , Pruebas Neuropsicológicas , Antioxidantes , Disfunción Cognitiva/etiología , Superóxido Dismutasa
10.
Dalton Trans ; 50(45): 16685-16693, 2021 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-34758054

RESUMEN

In this study, we reported the covalent post-synthetic modification (PSM) of a luminescent complex to achieve aggregation-induced emission (AIE), prepared using the Schiff base reaction of TPE-CHO and HLC-NH2, denoted by HLC-NH2-TPE. HLC-NH2 formed a 2D luminescent complex which was constructed using 4,4'-diamino-[1,1'-biphenyl]-2,2'-dicarboxylic acid and zinc ions via a solvothermal reaction. HLC-NH2-TPE inherited the luminescence properties of HLC-NH2 and exhibited noticeable AIE properties in response to environmental viscosities and temperature changes. Interestingly, HLC-NH2-TPE displayed a time-dependent luminescence conversion phenomenon in a mixed solution of DMF/H2O (v : v/1 : 9).

11.
Inorg Chem ; 60(21): 16474-16483, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34657429

RESUMEN

Using multifunctional organic ligands with multiple acidic groups (carboxylate and sulfonate groups) to synthesize metal-organic frameworks (MOFs) bearing effective H-bond networks is a promising strategy to obtain highly proton conductive materials. In this work, a highly stable two-dimensional MOF, [CuII5CuI2(µ3-OH)4(H2O)6(L)2(H2L)2]·3H2O (denoted as YCu161; H3L = 6-sulfonaphthalene-1,4-dicarboxylic acid) containing mixed-valence [CuII5CuI2(µ3-OH)4]8+ subunits, was successfully prepared. It exhibited excellent stability and temperature- and humidity-dependent proton conduction properties. Its optimal proton conductivity reached 1.84 × 10-3 S cm-1 at 90 °C and 98% relative humidity. On the basis of a crystal structure analysis, water vapor adsorption test results, and activation energy calculations, we deduced the proton conduction pathway and mechanism. Apparently, uncoordinated sulfonic and carboxyl groups and a network of abundant H-bonds inside the framework were responsible for the efficient proton transfer. Therefore, the strategy of selecting suitable bifunctional ligands to construct two-dimensional Cu-cluster-based MOFs with excellent proton conductivity is feasible.

12.
Gen Hosp Psychiatry ; 71: 108-113, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34000518

RESUMEN

OBJECTIVE: Depressive symptoms and cognitive dysfunction are common in patients with schizophrenia and depressive disorder. This study aimed at exploring whether and how depressive symptoms were correlated with neuro-cognitive impairment in patients with never-treated first-episode (NTFE) schizophrenia. METHODS: The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was administered to 79 patients and 80 healthy controls to assess neuropsychological function. For all patients, the 17-item Hamilton Depression Rating Scale (HAMD-17) was adopted to evaluate depressive symptoms, and the Positive and Negative Syndrome Scale (PANSS) was utilized to assess psychopathological symptoms. RESULTS: Thirty-nine patients (49.37%) met the criteria for comorbid depressive symptoms. The RBANS total and the four index scores in the patients were significantly lower than those in the healthy controls. Further, compared with patients without depressive symptoms, patients with depressive symptoms scored lower in attention index, but higher in PANSS general psychopathology and total scores. The HAMD-17 total score was significantly correlated with attention, PANSS total, and PANSS general psychopathology scores. Moreover, multiple regression analysis identified education and HAMD-17 score as the contributors to attention. CONCLUSION: Our results suggest that the rate of depressive symptoms in NTFE schizophrenia is high, which is correlated with neuro-cognitive impairment, especially attention and psychopathology.


Asunto(s)
Disfunción Cognitiva , Esquizofrenia , China/epidemiología , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Depresión/epidemiología , Humanos , Análisis Multivariante , Escalas de Valoración Psiquiátrica , Esquizofrenia/epidemiología
13.
Neural Regen Res ; 16(3): 537-542, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32985484

RESUMEN

Dexanabinol (HU-211) is an artificially synthesized cannabinoid derivative that exerts neuroprotective effects through anti-inflammatory and antioxidant effects. Curcumin exhibits antidepressant effects in the treatment of major depressive disorder. To investigate the antidepressant effects of solid lipid nanoparticles loaded with both curcumin and dexanabinol, and the underlying mechanisms associated with this combination, we established wild-type (CBR1+/+) and cannabinoid receptor 1 (CBR1) knockout (CBR1-/-) mouse models of major depressive disorder, through the intraperitoneal injection of corticosterone, for 3 successive days, followed by treatment with intraperitoneal injections of solid lipid nanoparticles loading with curcumin (20 mg/kg) and dexanabinol (0.85 mg/kg), for 2 successive days. Our results revealed that solid lipid nanoparticle loading with curcumin and dexanabinol increased the mRNA and protein expression levels of the mature neuronal markers neuronal nuclei, mitogen-activated protein 2, and neuron-specific beta-tubulin III, promoted the release of dopamine and norepinephrine, and increased the mRNA expression of CBR1 and the downstream genes Rasgef1c and Egr1, and simultaneously improved rat locomotor function. However, solid lipid nanoparticles loaded with curcumin and dexanabinol had no antidepressant effects on the CBR1-/- mouse models of major depressive disorder. This study was approved by the Institutional Ethics Committee of Tongji Hospital of Tongji University, China (approval No. 2017-DW-020) on May 24, 2017.

14.
Int J Ophthalmol ; 13(12): 1895-1900, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33344187

RESUMEN

AIM: To investigate the clinical efficacy and safety of femtosecond laser-assisted steepest-meridian clear corneal incisions for correcting preexisting corneal astigmatism performed at the time of cataract surgery. METHODS: This prospective case series study comprised consecutive age-related cataract patients with corneal regular astigmatism (range: +0.75 to +2.50 D) who had femtosecond laser-assisted steepest-meridian clear corneal incisions (single or paired). Corneal astigmatism was performed with the Pentacam preoperatively and 3mo postoperatively. Total corneal astigmatism and steepest-meridian measured in the 3-mm central zone were used to guide the location, size and number of clear corneal incision. The vector analysis of astigmatic change was performed using the Alpins method. RESULTS: Totally 138 eyes of 138 patients were included. The mean preoperative corneal astigmatism was 1.31±0.41 D, and was significantly reduced to 0.69±0.34 D (equivalent to difference vector) after surgery (P<0.01). The surgically-induced astigmatism was 1.02±0.54 D. The correction index (ratio of target induced astigmatism and surgically-induced astigmatism: 0.72±0.36) as well as the magnitude of error (difference between surgically-induced astigmatism and target induced astigmatism: -0.29±0.51) represented a slight under correction. For angle of error, the arithmetic mean was 1.11±13.70, indicating no significant systematic alignment errors. CONCLUSION: Femtosecond-assisted steepest-meridian clear corneal incision is a fast, customizable, adjustable, precise, and safe technique for the reduction of low to moderate corneal astigmatism during cataract surgery.

15.
J Cell Mol Med ; 24(14): 7907-7914, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32529705

RESUMEN

Increased expression and activity of cardiac and circulating cathepsin D and soluble fms-like tyrosine kinase-1 (sFlt-1) have been demonstrated to induce and promote peripartum cardiomyopathy (PPCM) via promoting cleavage of 23-kD prolactin (PRL) to 16-kD PRL and neutralizing vascular endothelial growth factor (VEGF), respectively. We hypothesized that activation of Hes1 is proposed to suppress cathepsin D via activating Stat3, leading to alleviated development of PPCM. In the present study, we aimed to investigate the role of Notch1/Hes1 pathway in PPCM. Pregnant mice between prenatal 3 days and postpartum 3 weeks were fed with LY-411575 (a notch inhibitor, 10 mg/kg/d). Ventricular function and pathology were evaluated by echocardiography and histological analysis. Western blotting analysis was used to examine the expression at the protein level. The results found that inhibition of Notch1 significantly promoted postpartum ventricular dilatation, myocardial hypertrophy and myocardial interstitial fibrosis and suppressed myocardial angiogenesis. Western blotting analysis showed that inhibition of Notch1 markedly increased cathepsin D and sFlt-1, reduced Hes1, phosphorylated Stat3 (p-Stat3), VEGFA and PDGFB, and promoted cleavage of 23k-D PRL to 16-kD PRL. Collectively, inhibition of Notch1/Hes1 pathway induced and promoted PPCM via increasing the expressions of cathepsin D and sFlt-1. Notch1/Hes1 was a promising target for prevention and therapeutic regimen of PPCM.


Asunto(s)
Cardiomiopatías/etiología , Cardiomiopatías/metabolismo , Periodo Periparto/metabolismo , Receptor Notch1/metabolismo , Transducción de Señal , Animales , Biomarcadores , Cardiomegalia/diagnóstico , Cardiomegalia/etiología , Cardiomegalia/metabolismo , Cardiomiopatías/sangre , Cardiomiopatías/diagnóstico , Catepsina D/metabolismo , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Ecocardiografía , Femenino , Fibrosis , Proteínas de la Membrana/metabolismo , Ratones , Embarazo , Proteolisis , Remodelación Ventricular
16.
Biochem Cell Biol ; 98(2): 106-111, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32069075

RESUMEN

Both the Notch1 and Keap1-Nrf2 signaling pathways have cardioprotective effects, but the role of Notch1-Nrf2 crosstalk in myocardial ischemia-reperfusion injury is unclear. In this study, we established hypoxia-reoxygenation in neonate rat myocardial cells and employed γ-secretase inhibitor and curcumin to inhibit and activate the Notch1 and Keap1-Nrf2 signaling pathways, respectively. We found that the combined action of the Notch1 and Keap1-Nrf2 signaling pathways significantly increased cardiomyocyte viability, inhibited cardiomyocyte apoptosis, reduced the formation of reactive oxygen species, and increased antioxidant activities. In conclusion, these findings suggest that Notch1-Nrf2 crosstalk exerts myocardial protection by reducing the formation of reactive oxygen species.


Asunto(s)
Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Isquemia Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Receptor Notch1/metabolismo , Animales , Animales Recién Nacidos , Antioxidantes/metabolismo , Apoptosis , Hipoxia de la Célula , Núcleo Celular/metabolismo , Proliferación Celular , Supervivencia Celular , Citoplasma/metabolismo , Regulación Neoplásica de la Expresión Génica , Hipoxia , Miocardio/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Transducción de Señal
17.
J Cell Mol Med ; 24(5): 3183-3191, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31975567

RESUMEN

Mitochondrial fusion and fission dynamic are critical to the myocardial protection against ischaemia-reperfusion injury. Notch1 signalling plays an important role in heart development, maturation and repair. However, the role of Notch1 in the myocardial mitochondrial fusion and fission dynamic remains elusive. Here, we isolated myocardial cells from rats and established myocardial ischaemia-reperfusion injury (IRI) model. We modulated Notch1, MFN1 and DRP1 expression levels in myocardial cells via infection with recombinant adenoviruses. The results showed that Notch1 improves the cell viability and mitochondrial fusion in myocardiocytes exposed to IRI. These improvements were dependent on the regulation of MFN1 and DRP1. On the mechanism, we found that MNF1 is transcriptionally activated by RBP-Jk in myocardiocytes. Notch1 also improves the mitochondrial membrane potential in myocardiocytes exposed to IRI. Moreover, we further confirmed the protection of the Notch1-MFN1/Drp1 axis on the post-ischaemic recovery of myocardial performance is associated with the preservation of the mitochondrial structure. In conclusion, this study presented a detailed mechanism by which Notch1 signalling improves mitochondrial fusion during myocardial protection.


Asunto(s)
Dinaminas/genética , GTP Fosfohidrolasas/genética , Proteínas de Transporte de Membrana Mitocondrial/genética , Infarto del Miocardio/genética , Daño por Reperfusión Miocárdica/genética , Receptor Notch1/genética , Animales , Apoptosis/genética , Supervivencia Celular/genética , Regulación de la Expresión Génica/genética , Masculino , Potencial de la Membrana Mitocondrial/genética , Mitocondrias Cardíacas/genética , Dinámicas Mitocondriales/genética , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/patología , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Sustancias Protectoras/farmacología , Ratas , Transducción de Señal/genética
18.
Dalton Trans ; 48(32): 12159-12167, 2019 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-31328744

RESUMEN

A new cadmium-based coordination polymer (CP), [Cd3(bpe)2(ceba)2(fa)2(H2O)2]n (1; fa = formate anions), was constructed by solvothermal reactions of cadmium nitrates with trans-1,2-bis(4'-pyridyl)ethylene ligand (bpe) and 4-(1-carboxy-ethoxy)-benzoic acid (H2ceba). The [2 + 2] photodimerization reaction of CP 1 under UV irradiation generated the corresponding photoproduct [Cd3(rctt-tpcb)(ceba)2(fa)2(H2O)2]n (1a; rctt-tpcb = tetrakis(4-pyridyl)-cyclobutane) via a single-crystal-to-single-crystal (SCSC) transformation. Single crystal X-ray diffraction unveiled that CPs 1 and 1a have similar 2D layered structures, except that rctt-tpcb replaced a pair of bpe ligands in the latter. Furthermore, CPs 1 and 1a are good bifunctional luminescent sensors that can detect Fe3+ and Cr2O72- ions in a mixed medium of water and DMF and display high sensitivity, selectivity, and anti-jamming capability for the recognition of Fe3+ and Cr2O72- ions. Moreover, we also examine in detail the possible luminescent quenching mechanisms of 1 and 1a toward Fe3+ and Cr2O72- ions.

19.
Clin Sci (Lond) ; 133(9): 1085-1096, 2019 05 31.
Artículo en Inglés | MEDLINE | ID: mdl-31040165

RESUMEN

Nuclear receptor binding SET domain 2 (NSD2)-mediated metabolic reprogramming has been demonstrated to regulate oncogenesis via catalyzing the methylation of histones. The present study aimed to investigate the role of NSD2-mediated metabolic abnormality in pulmonary arterial hypertension (PAH). Monocrotaline (MCT)-induced PAH rat model was established and infected with adeno-associated virus carrying short hairpin RNA (shRNA) targeting NSD2. Hemodynamic parameters, ventricular function, and pathology were evaluated by microcatheter, echocardiography, and histological analysis. Metabolomics changes in lung tissue were analyzed by LC-MS. The results showed that silencing of NSD2 effectively ameliorated MCT-induced PAH and right ventricle dysfunction, and partially reversed pathological remodeling of pulmonary artery and right ventricular hypertrophy. In addition, the silencing of NSD2 markedly reduced the di-methylation level of H3K36 (H3K36me2 level) and inhibited autophagy in pulmonary artery. Non-targeted LC-MS based metabolomics analysis indicated that trehalose showed the most significant change in lung tissue. NSD2-regulated trehalose mainly affected ABC transporters, mineral absorption, protein digestion and absorption, metabolic pathways, and aminoacyl-tRNA biosynthesis. In conclusion, we reveal a new role of NSD2 in the pathogenesis of PAH related to the regulation of trehalose metabolism and autophagy via increasing the H3K36me2 level. NSD2 is a promising target for PAH therapy.


Asunto(s)
Autofagia/fisiología , Hipertensión Pulmonar Primaria Familiar/tratamiento farmacológico , N-Metiltransferasa de Histona-Lisina/genética , Hipertrofia Ventricular Derecha/metabolismo , Hipertensión Arterial Pulmonar/genética , Animales , Autofagia/efectos de los fármacos , Modelos Animales de Enfermedad , Hemodinámica/efectos de los fármacos , Hipertrofia Ventricular Derecha/tratamiento farmacológico , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Masculino , Monocrotalina/farmacología , Arteria Pulmonar/efectos de los fármacos , Ratas Sprague-Dawley , Remodelación Vascular/efectos de los fármacos
20.
Inorg Chem ; 58(5): 3145-3155, 2019 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-30758199

RESUMEN

A family of two-dimensional (2D) Zn-based metal-organic frameworks (MOFs) with exitonic emission have been successfully synthesized under hydrothermal conditions. When isophthalic acid ligands with different substitutions are introduced, the crystal structures and fluorescence properties are significantly changed. Hirshfeld surface calculation is used to study the nuances of diverse substitutions during the construction of all of the crystals. The solid fluorescence results indicate that there are obvious two-channel emissions, including intralayer excimers and interlayer trapped excitons, both in 1 and 2 with a double-layer structure and in 3 with a single-layer structure, mainly exhibiting intralayer emission. Furthermore, the fluorescence changes on morphology transformations are explored after mechanical exfoliation consisting of grinding and ultrasonicaation of MOFs 1-3. The regulation and control of crystal structure and morphology can suppress emission based on interlayer excitons, achieving adjustment of the overall emitting color. To the best of our knowledge, this is the first report of 2D bilayer MOFs with dual-channel emissions, which provides a new structural model for synthesizing new exciton materials.

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