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1.
Neurotox Res ; 42(4): 35, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39008165

RESUMEN

This study elucidates the molecular mechanisms by which FABP3 regulates neuronal apoptosis via mitochondrial autophagy in the context of cerebral ischemia-reperfusion (I/R). Employing a transient mouse model of middle cerebral artery occlusion (MCAO) established using the filament method, brain tissue samples were procured from I/R mice. High-throughput transcriptome sequencing on the Illumina CN500 platform was performed to identify differentially expressed mRNAs. Critical genes were selected by intersecting I/R-related genes from the GeneCards database with the differentially expressed mRNAs. The in vivo mechanism was explored by infecting I/R mice with lentivirus. Brain tissue injury, infarct volume ratio in the ischemic penumbra, neurologic deficits, behavioral abilities, neuronal apoptosis, apoptotic factors, inflammatory factors, and lipid peroxidation markers were assessed using H&E staining, TTC staining, Longa scoring, rotation experiments, immunofluorescence staining, and Western blot. For in vitro validation, an OGD/R model was established using primary neuron cells. Cell viability, apoptosis rate, mitochondrial oxidative stress, morphology, autophagosome formation, membrane potential, LC3 protein levels, and colocalization of autophagosomes and mitochondria were evaluated using MTT assay, LDH release assay, flow cytometry, ROS/MDA/GSH-Px measurement, transmission electron microscopy, MitoTracker staining, JC-1 method, Western blot, and immunofluorescence staining. FABP3 was identified as a critical gene in I/R through integrated transcriptome sequencing and bioinformatics analysis. In vivo experiments revealed that FABP3 silencing mitigated brain tissue damage, reduced infarct volume ratio, improved neurologic deficits, restored behavioral abilities, and attenuated neuronal apoptosis, inflammation, and mitochondrial oxidative stress in I/R mice. In vitro experiments demonstrated that FABP3 silencing restored OGD/R cell viability, reduced neuronal apoptosis, and decreased mitochondrial oxidative stress. Moreover, FABP3 induced mitochondrial autophagy through ROS, which was inhibited by the free radical scavenger NAC. Blocking mitochondrial autophagy with sh-ATG5 lentivirus confirmed that FABP3 induces mitochondrial dysfunction and neuronal apoptosis by activating mitochondrial autophagy. In conclusion, FABP3 activates mitochondrial autophagy through ROS, leading to mitochondrial dysfunction and neuronal apoptosis, thereby promoting cerebral ischemia-reperfusion injury.


Asunto(s)
Apoptosis , Autofagia , Proteína 3 de Unión a Ácidos Grasos , Mitocondrias , Neuronas , Daño por Reperfusión , Animales , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Apoptosis/fisiología , Autofagia/fisiología , Neuronas/metabolismo , Neuronas/patología , Ratones , Mitocondrias/metabolismo , Masculino , Proteína 3 de Unión a Ácidos Grasos/metabolismo , Proteína 3 de Unión a Ácidos Grasos/genética , Ratones Endogámicos C57BL , Infarto de la Arteria Cerebral Media/patología , Infarto de la Arteria Cerebral Media/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Estrés Oxidativo/fisiología
2.
Org Lett ; 25(22): 4050-4055, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37235701

RESUMEN

Herein, we report a visible-light-induced three-component reaction involving [1.1.1]propellane, diazoates, and various heterocycles for the synthesis of 3-heteroarylbicyclo[1.1.1]pentane-1-acetates. Throughout this reaction, the radicals generated from diazoate species react with [1.1.1]propellane in an addition reaction to form bicyclo[1.1.1]pentane (BCP) radicals that subsequently react with heterocycles, leading to the formation of 1,3-disubstituted BCP acetates. Notably, this methodology exhibits excellent functional group compatibility, high atom economy, and mild reaction conditions, thus facilitating suitable synthetic access to 1,3-disubstituted BCP acetates.


Asunto(s)
Acetatos , Pentanos , Luz
3.
Clin Lab ; 68(4)2022 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-35443594

RESUMEN

BACKGROUND: Vacuum blood collection tubes with separator gels have made biochemical testing considerably more convenient and provided test samples with better quality; however, the separator gel composition is complex, and it is easy to be polluted by some chemical substances that affect the accuracy of the test results if the raw material control is not strict. METHODS: This study reported a case of pseudo elevation of serum calcium. RESULTS: The pseudo elevation of serum calcium was caused by separator gel calcium contamination of the new batch of vacuum tube (s2005030). CONCLUSIONS: We recommend that clinical laboratories verify the performance of each new batch of vacuum blood collection tubes before using them to prevent the occurrence of adverse events, ensure the accuracy of test results, and provide better clinical services.


Asunto(s)
Recolección de Muestras de Sangre , Calcio , Recolección de Muestras de Sangre/métodos , Geles , Humanos
4.
Clin Lab ; 67(9)2021 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-34542980

RESUMEN

BACKGROUND: D-dimer is a molecular marker of fibrin degradation and fibrinolytic system activation and is an effective indicator for early diagnosis of thrombotic diseases, monitoring of thrombolytic therapy, and efficacy evaluation; therefore, the accuracy of D-dimer test results is of great significance to the diagnosis and treatment of diseases in clinical practice. METHODS: This paper reports two cases of pseudoelevation of plasma D-dimer levels by different test systems. RESULTS: In case 1, the abnormal increases in the results of the ACL TOP 700 analyzer were considered to be the pseudoelevation caused by interferences, and the abnormal increases in the STA-R Max results were considered to be the pseudoelevation caused by interferences in case 2. CONCLUSIONS: Laboratories should be equipped with two different brands of test systems and reagents to identify suspicious test results in a timely manner and avoid adverse events.


Asunto(s)
Productos de Degradación de Fibrina-Fibrinógeno , Trombosis , Fibrina , Humanos , Terapia Trombolítica
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