RESUMEN
Neonatal hypoxic ischemia is one of the leading causes of permanent morbidity and mortality in newborns, which is caused by difficulty in supplying blood and oxygen to brain tissue and is often associated with epilepsy, cerebral palsy, death, short-term or long-term neurological and cognitive impairment. In recent years, the clinical therapeutic effects of noble gases have been gradually discovered and recognized. Numerous studies have shown that noble gases have unique neuroprotective effects to restore damaged nerve and relieve symptoms in patients. Although research on the neuroprotective mechanisms of xenon and argon has yielded a lot of results, studies on helium have stalled. Helium is a colorless, odorless, monoatomic inert gas. The helium has no hemodynamic or neurocognitive side effects and can be used as an ideal pre-adaptor for future clinical applications. In recent years, studies have shown that heliox (a mixture of helium and oxygen) pretreatment can protect the heart, brain, liver and intestine from damage in several animal models, where a variety of signaling pathways have been proved to be involved. There are numerous studies on it even though the mechanism of helium for protecting newborns has not been fully elucidated. It is urgent to find an effective treatment due to the high death rate and disability rate of neonatal hypoxic ischemia. It is believed that helium will be approved safely and effectively for clinical use in the near future.
Asunto(s)
Helio , Fármacos Neuroprotectores , Animales , Helio/uso terapéutico , Humanos , Recién Nacido , Isquemia , Fármacos Neuroprotectores/uso terapéutico , OxígenoRESUMEN
AIMS: Acyl-CoA synthetase long chain family member 4 (ACSL4) is closely related to tumor genesis and development in certain tissues. However, the function of ACSL4 in early brain injury (EBI) caused by subarachnoid hemorrhage (SAH) is unclear. In this study, we investigated the expression patterns and role of ACSL4 in SAH and post-SAH EBI using a rat model of SAH. METHODS: The rat model of SAH was induced by autologous blood injection into the prechiasmatic cistern of rats. We also used two specific inhibitors of ferroptosis (Ferrostatin-1 and Liproxstatin-1) to investigate the role of ferroptosis in EBI. RESULTS: We found that ACSL4 levels in brain tissue increased significantly in post-SAH EBI. Inhibiting the expression of ACSL4 using small interfering RNAs alleviated inflammation, blood-brain barrier (BBB) impairment, oxidative stress, brain edema, and behavioral and cognitive deficits, and increased the number of surviving neurons, after SAH. Similar effects were obtained by suppressing ferroptosis. CONCLUSIONS: ACSL4 exacerbated SAH-induced EBI by mediating ferroptosis. These findings may provide a theoretical basis for potential therapy aimed at alleviating post-SAH EBI.
Asunto(s)
Lesiones Encefálicas/metabolismo , Coenzima A Ligasas/biosíntesis , Ferroptosis/fisiología , Hemorragia Subaracnoidea/metabolismo , Animales , Lesiones Encefálicas/patología , Masculino , Aprendizaje por Laberinto/fisiología , Ratas , Ratas Sprague-Dawley , Hemorragia Subaracnoidea/patologíaRESUMEN
INTRODUCTION: S100 calcium-binding protein A8 (S100A8) is also known as macrophage-related protein 8, which is involved in various pathological processes in the central nervous system post-traumatic brain injury (TBI), and plays a critical role in inducing inflammatory cytokines. Accumulating evidences have indicated that toll-like receptor 4 (TLR4) is considered to be involved in inflammatory responses post TBI. The present study was designed to analyze the hypothesis that S100A8 is the key molecule that induces inflammation via TLR4 in TBI. METHODS: The weight-drop TBI model was used and randomly implemented on mice that were categorized into six groups: Sham, NS, S100A8, S100A8+TAK-242, TBI, and TBI+TAK-242 groups. In the S100A8+TAK-242 and TBI+TAK-242 groups, at half an hour prior to the intracerebroventricular administration of S100A8 or TBI, mice were intraperitoneally treated with TAK-242 that acts as a selective antagonist and inhibitor of TLR4. Furthermore, the protein recombinant of S100A8 was injected into the lateral ventricle of the brain of mice in the S100A8 and S100A8+TAK-242 groups. Sterile normal saline was injected into the lateral ventricle in the NS group. To evaluate the association between S100A8 and TLR4, Western blot, immunofluorescence, enzyme-linked immunosorbent assay (ELISA), and Nissl staining were employed. Simultaneously, the neurological score and brain water content were assessed. In the in vitro analysis, BV-2 microglial cells were stimulated with lipopolysaccharide LPS or S100A8 recombinant protein, with or without TAK-242. The expression of the related proteins was subsequently detected by Western blot or enzyme-linked immunosorbent assay. RESULTS: The levels of S100A8 protein and pro-inflammatory cytokines were significantly elevated after TBI. There was a reduction in the neurological scores of non-TBI animals with remarkable severe brain edema after the intracerebroventricular administration of S100A8. Furthermore, the TLR4, p-p65, and myeloid differentiation factor 88 (MyD88) levels were elevated after the administration of S100A8 or TBI, which could be restored by TAK-242. Meanwhile, in the in vitro analysis, due to the stimulation of S100A8 or LPS, there was an upregulation of p-p65 and MyD88, which could also be suppressed by TAK-242. CONCLUSION: The present study demonstrated that the TLR4-MyD88 pathway was activated by S100A8, which is essential for the development of inflammation in the brain after TBI.
RESUMEN
BACKGROUND: Invasion growth is the most characteristic biological phenotype of glioblastoma, but the molecular mechanism in glioma cell invasion is poorly understood. Recent data have showed that microRNA plays an essential role in tumor invasion. Our study aimed to explore the mechanism of miR-7 involved in the control of glioblastoma cell invasion. METHODS: Glioma cell invasion was evaluated by transwell and scratch assays after up-regulation of miR-7 using miR-7 mimics in U87 and U251 cells. Luciferase reporter assay was used to determine focal adhesion kinase (FAK) as a target of miR-7. The levels of miR-7, matrix metalloproteinases (MMP)-2 and MMP-9 mRNA were detected by PCR assay, and the levels of FAK, MMP-2, MMP-9, total and phosphorylation serine/threonine kinase (AKT), and extracellular signal-regulated kinase (ERK) 1/2 were measured by Western blotting analysis. RESULTS: Over-expression of miR-7 inhibited the invasion and migration activity of U87 and U251 cells. And up-regulation of miR-7 reduced FAK protein expression, Further, luciferase reporter assay showed that miR-7 modulated FAK expression directly by binding 3'UTR of FAK mRNA. In addition, miR-7 repressed p-ERK1/2 and p-AKT level, MMP-2 and MMP-9 expression. Finally, the inverse relationship between FAK and miR-7 expression was certificated in human glioma tissues. CONCLUSION: To our knowledge, these data indicate for the first time that miR-7 directly regulates cell invasion by targeting FAK in glioblastoma and that miR-7 could be a potential therapeutic target for glioblastoma intervention.
Asunto(s)
Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Glioblastoma/enzimología , MicroARNs/metabolismo , Western Blotting , Línea Celular Tumoral , Proteína-Tirosina Quinasas de Adhesión Focal/genética , Glioblastoma/genética , Humanos , Técnicas In Vitro , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , MicroARNs/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Houttuynia cordata is one of the most potential medicinal and edible wild herb whose resources have decreased sharply due to excessive exploitation. Besides its slow agamic propagation, problems of browning and non-dedifferentiation have prevented the application of micropropagation in H. cordata. Through 4 week pre-culture in darkness and wounding after 1 week pre-culture, the browning rate of leaf explants decreased significantly and resulted in efficient regeneration (20.64 +/- 5.94 adventitious buds per explant) on the induction medium. The protocol shall facilitate conservation and commercial cultivation of the endangered species.