RESUMO
MYB is a key regulator of hematopoiesis and erythropoiesis, and dysregulation of MYB is closely involved in the development of leukemia, however the mechanism of MYB regulation remains still unclear so far. Our previous study identified a long noncoding RNA (lncRNA) derived from the -34 kb enhancer of the MYB locus, which can promote MYB expression, the proliferation and migration of human leukemia cells, and is therefore termed MY34UE-AS. Then the interacting partner proteins of MY34UE-AS were identified and studied in the present study. hnRNPA0 was identified as a binding partner of MY34UE-AS through RNA pulldown assay, which was further validated through RNA immunoprecipitation (RIP). hnRNPA0 interacted with MY34UE-AS mainly through its RRM2 domain. hnRNPA0 overexpression upregulated MYB and increased the proliferation and migration of K562 cells, whereas hnRNPA0 knockdown showed opposite effects. Rescue experiments showed MY34UE-AS was required for above mentioned functions of hnRNPA0. These results reveal that hnRNPA0 is involved in leukemia through upregulating MYB expression by interacting with MY34UE-AS, suggesting that the hnRNPA0/MY34UE-AS axis could serve as a potential target for leukemia treatment.
Assuntos
Proliferação de Células , Leucemia , Proteínas Proto-Oncogênicas c-myb , RNA Longo não Codificante , Humanos , Linhagem Celular Tumoral , Movimento Celular/genética , Elementos Facilitadores Genéticos , Regulação Leucêmica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas/genética , Células K562 , Leucemia/genética , Leucemia/metabolismo , Leucemia/patologia , Ligação Proteica , Proteínas Proto-Oncogênicas c-myb/metabolismo , Proteínas Proto-Oncogênicas c-myb/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
Temporal lobe epilepsy (TLE) is common intractable epilepsy that affects the patient's lives. The circular RNA circ_ANKMY2 (circ_ANKMY2) has been reported to be abnormally expressed in TLE. Nevertheless, the role and mechanism of circ_ANKMY2 in TLE are unclear. A human neuroblastoma cell line (SK-N-AS) was used for a series of studies. Expression levels of circ_ANKMY2, miR-106b-5p, and Forkhead Box Protein 1 (FOXP1) mRNA in TLE tissues were assessed through quantitative real-time polymerase chain reaction (qRT-PCR). Cell colony formation, proliferation, and apoptosis were determined by cell colony formation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), or flow cytometry assays. The levels of FOXP1 protein, Ki67, B cell lymphoma (Bcl-2), Bcl-2 Associated X (Bax), and Cleaved caspase-3 were evaluated by western blot analysis. The relationship between circ_ANKMY2 or FOXP1 and miR-106b-5p was verified with dual-luciferase reporter assay. We observed that circ_ANKMY2 and FOXP1 expression were reduced while miR-106b-5p expression was increased in TLE tissues. Overexpression of circ_ANKMY2 decreased spontaneous recurrent seizures (SRSs) in rat TLE model and blocked cell colony formation, proliferation, and induced cell apoptosis in SK-N-AS cells. Importantly, circ_ANKMY2 was verified as a sponge for miR-106b-5p. In addition, miR-106b-5p mimics abolished circ_ANKMY2 elevation-mediated effects on colony formation, proliferation, and apoptosis of SK-N-AS cells. Also, FOXP1 served as a target for miR-106b-5p. And FOXP1 silencing overturned the effects of miR-106b-5p inhibitors on the colony formation, proliferation, and apoptosis of SK-N-AS cells. In sum, circ_ANKMY2 modulated TLE advancement via regulation of FOXP1 expression through sponging miR-106b-5p, and circ_ANKMY2 might be an underlying target for the improvement of TLE.
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Epilepsia do Lobo Temporal/metabolismo , Fatores de Transcrição Forkhead/metabolismo , MicroRNAs/metabolismo , RNA Circular/metabolismo , Proteínas Repressoras/metabolismo , Animais , Apoptose/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Progressão da Doença , Regulação para Baixo , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Ratos Wistar , Convulsões/metabolismo , Regulação para CimaRESUMO
TP53-induced glycolysis and apoptosis regulator (TIGAR) activates the pentose phosphate pathway (PPP), which feeds reduced nicotinamide adenine dinucleotide phosphate (NADPH) to the antioxidant glutathione pathway. Oxidative stress-induced neuronal apoptosis is the pathological basis of several neurological disorders, including epilepsy. To determine the potential anti-epileptic action TIGAR in a rodent kainic acid (KA)-induced seizure model. Seizures were induced by the intra-cerebroventricular injection of KA, followed by injection of empty or TIGAR-expressing lentiviral vectors. Immunofluorescence was used to detect the localization of TIGAR in the cortices and hippocampi, and the expression levels of relevant proteins were determined by Western blotting. Oxidative stress-related markers were detected using commercially available kits. Neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining. TIGAR were mainly expressed in the neurons and rarely located in the astrocytes, and increased in the cortices and hippocampi of KA-treated rats in a time-dependent manner. Lentivirus-mediated TIGAR overexpression significantly decreased the oxidative stress and neuronal apoptosis induced by KA, resulting in prolonged seizure latency and lower Racine scores. Our findings indicate that TIGAR has anti-epileptic, anti-oxidant and anti-apoptotic effects, and is therefore a promising therapeutictarget for epilepsy.
Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Apoptose , Neurônios/patologia , Estresse Oxidativo , Monoéster Fosfórico Hidrolases/metabolismo , Convulsões/patologia , Animais , Hipocampo/patologia , Ácido Caínico , Masculino , Neurônios/metabolismo , Ratos Sprague-DawleyRESUMO
PURPOSE: The association between intracranial internal carotid artery (IICA) calcification and lacunes, white matter hyperintensity (WMH), and cerebral microbleeds (CMBs) has been well researched. However, enlarged cerebral perivascular space (PVS) has not yet been reported to correlate with intracranial internal carotid artery calcification. Therefore, the primary aim of this study was to investigate the relationship between IICA calcification and enlarged PVS. METHODS: A total of 189 patients with ischemic stroke in the middle cerebral artery territory who presented within 7 days of ictus from 2012 to 2015 were enrolled respectively. All patients were required to have undergone head computed tomography, magnetic resonance imaging, susceptibility-weighted magnetic resonance imaging, magnetic resonance angiography, or computed tomography angiography. Clinical characteristics were recorded. IICA calcification and enlarged PVS were semi-quantitatively evaluated, and the presence of lacunes, WMH, and CMBs was recorded. RESULTS: Of the 189 patients, 63.5% were male. Mean age of the patients was 68.6 ± 12.2 years. There were 104 patients with IICA calcification. Age, diabetes mellitus, lacunes, and white matter hyperintensity were significantly associated with IICA calcification (P < 0.05). Multivariate logistic regression analysis showed that age, diabetes mellitus, and lacunes were independent predictors of IICA calcification (P < 0.05). A lower risk of IICA calcification was found in patients with a higher enlarged PVS score (P = 0.004). CONCLUSION: Higher enlarged PVS scores were associated with a lesser degree of IICA calcification. There appears to be a relationship between reduced risk of IICA calcification and enlarged PVS.
Assuntos
Isquemia Encefálica/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Neuroimagem/métodos , Calcificação Vascular/diagnóstico por imagem , Idoso , Isquemia Encefálica/patologia , Estenose das Carótidas/patologia , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Hemorragias Intracranianas/diagnóstico por imagem , Hemorragias Intracranianas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Calcificação Vascular/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologiaRESUMO
Acclimatization to high-altitude, long-term hypoxia (LTH) reportedly alters cerebral artery contraction-relaxation responses associated with changes in K(+) channel activity. We hypothesized that to maintain oxygenation during LTH, basilar arteries (BA) in the ovine adult and near-term fetus would show increased large-conductance Ca(2+) activated potassium (BK) channel activity. We measured BK channel activity, expression, and cell surface distribution by use of patch-clamp electrophysiology, flow cytometry, and confocal microscopy, respectively, in myocytes from normoxic control and LTH adult and near-term fetus BA. Electrophysiological data showed that BK channels in LTH myocytes exhibited 1) lowered Ca(2+) set points, 2) left-shifted activation voltages, and 3) longer dwell times. BK channels in LTH myocytes also appeared to be more dephosphorylated. These differences collectively make LTH BK channels more sensitive to activation. Studies using flow cytometry showed that the LTH fetus exhibited increased BK ß1 subunit surface expression. In addition, in both fetal groups confocal microscopy revealed increased BK channel clustering and colocalization to myocyte lipid rafts. We conclude that increased BK channel activity in LTH BA occurred in association with increased channel affinity for Ca(2+) and left-shifted voltage activation. Increased cerebrovascular BK channel activity may be a mechanism by which LTH adult and near-term fetal sheep can acclimatize to long-term high altitude hypoxia. Our findings suggest that increasing BK channel activity in cerebral myocytes may be a therapeutic target to ameliorate the adverse effects of high altitude in adults or of intrauterine hypoxia in the fetus.
Assuntos
Cálcio/metabolismo , Hipóxia/metabolismo , Ativação do Canal Iônico , Canais de Potássio Ativados por Cálcio de Condutância Alta/metabolismo , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Aclimatação , Fatores Etários , Altitude , Animais , Artéria Basilar/metabolismo , Artéria Basilar/fisiopatologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Idade Gestacional , Hipóxia/etiologia , Hipóxia/fisiopatologia , Imuno-Histoquímica , Cinética , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Potenciais da Membrana , Músculo Liso Vascular/fisiopatologia , Técnicas de Patch-Clamp , Fosforilação , Gravidez , OvinosRESUMO
BACKGROUND: Here we report a rare case of repeated transient Wallenberg's syndrome and discuss its mechanism. METHODS: Case report and literature review. RESULTS: A 57-year-old man was admitted for 1.5-month repeated transient Wallenberg's syndrome, including right-sided Horner's syndrome, lower limb weakness, and paresthesia on the right side of the body and face. His symptom appeared mostly during physical activity. Symptoms occurred nearly everyday and lasted from 5 minutes to 30 minutes. His cranial magnetic resonance imaging (MRI) including diffusion-weighted MRI imaging was normal, and his cervical contrast-enhanced magnetic resonance angiography reflected right vertebral artery hypoplasia. Twenty-four-hour electrocardiogram and electroencephalography showed no abnormalities. Echocardiography showed aortic valve calcification with moderate aortic stenosis, moderate aortic insufficiency, and dilated aorta. Dual-antiplatelets or warfarin (international normalized ratio reached 2.07) were not effective to reduce the attacks. CONCLUSIONS: Hemodynamic instability due to valve disease combined with right vertebral artery hypoplasia could lead to transient Wallenberg's syndrome. Antithrombotics are often ineffective for this kind of patients and the best therapy for them could be to cure their valve disease. Repeated transient Wallenberg's syndrome is rare and that caused by ipsilateral vertebral artery hypoplasia and severe valve disease has not been reported up till now to our knowledge, so it will widen the knowledge on etiologies of transient ischemic attacks and provide information and reference to cardiologists and neurologists in diagnosis and treatment for patients with similar clinical manifestations.
Assuntos
Lateralidade Funcional , Cardiopatias Congênitas/complicações , Doenças das Valvas Cardíacas/complicações , Síndrome Medular Lateral/complicações , Artéria Vertebral/patologia , Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Ecocardiografia , Síndrome de Horner/etiologia , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-IdadeRESUMO
Background: To investigate the expression levels of blood biomarkers interleukin-6 (IL-6), tumour necrosis factor (TNF-a), and intestinal fatty acid binding protein (iFABP) in patients with post-stroke depression (PSD), and their correlation with PSD occurrence. Methods: Clinical data of stroke patients admitted to the First People's Hospital of Wenling from December 2017 to December 2022 were retrospectively analyzed. Patients were classified into two groups based on their Hamilton Depression Rating Scale (HAMD) scores: PSD and nonPSD groups. The blood levels of IL-6, TNF-a, and iFABP were compared between the two groups, and their association with PSD occurrence was analyzed. Results: The PSD group had significantly higher levels of IL-6, TNF-a, and iFABP. The combined detection of these biomarkers demonstrated a greater predictive value for PSD occurrence compared to the individual detection of each biomarker. Conclusions: The study indicates that the levels of IL-6, TNF-a, and iFABP in the blood are significantly increased in patients with PSD. The combined detection of these biomarkers can effectively predict the occurrence of PSD, indicating high clinical value.
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Objective: To analyze and predict the progress of patients with lacunar infarction by analyzing the levels of serum NO, PGI2, and Ox-LDL produced by endothelial cells. Methods: 138 patients with lacunar infarction and 34 healthy people were selected. The selected samples were divided into progressive group, nonprogressive group, and control group for biochemical test and endothelial function test. The levels of serum NO, PGI2, and Ox-LDL were obtained. The observation indexes of different groups were compared for statistical analysis and multivariate logistic regression analysis. Results: The indexes of LI patients in the nonprogression group were different from those in the control group. The content of Ox-LDL in the nonprogression group was higher than that in the control group, while the indexes of serum NO and PGI2 were lower than that in the control group. The level of Ox-LDL in LI patients in the progressive group was much higher than that in healthy people in the control group seven days after admission, while the levels of serum NO and PGI2 were lower, and the difference of serum on was more obvious. The level of Ox-LDL in the progressive group was much higher than that in the nonprogressive group, while the levels of serum NO and PGI2 in the progressive group were lower, and the level of serum NO was significantly different from that in the nonprogressive group. Ox - LDL > 76.48 U/L, NO > 55.24 ummol/L, and PGI2 > 29.78 ng/L were independent risk factors for the progression of lacunar infarction. Conclusion: Because the patients with lacunar infarction have endothelium-dependent relaxation disorder, the changes of serum NO, PGI2, and Ox-LDL can be used as the evaluation index of the disease progress of patients with lacunar infarction and can be widely used in clinical detection.
Assuntos
Acidente Vascular Cerebral Lacunar , Infarto Cerebral , Progressão da Doença , Células Endoteliais , Epoprostenol/sangue , Humanos , Lipoproteínas LDL , Óxido Nítrico/sangueRESUMO
Dihydromyricetin (DMY) is a natural flavonoid that possesses a wide range of pharmacological properties. The aim of the present study was to determine whether DMY could protect against nerve cell injury following ischemic stroke through antioxidant and neuroprotective effects. The effects of DMY on the viability, oxidative stress and apoptosis of HT22 cells following oxygenglucose deprivation and reoxygenation (OGD/R) were examined using MTT, lactate dehydrogenase (LDH), superoxide (SOD), malondialdehyde (MDA), western blot and TUNEL assays. Furthermore, Wnt/ßcatenin signaling proteins in OGD/Rstimulated HT22 cells were detected in the presence or absence of DMY. In a separate experiment, the effect of DMY on OGD/Rinduced HT22 cell injury was also observed in the presence of the Wnt/ßcatenin inhibitor, XAV939. The results demonstrated that DMY had no impact on the survival of untreated HT22 cells, although DMY treatment significantly increased cell viability and inhibited cytotoxicity, oxidative stress and apoptosis following OGD/R. In addition, DMY upregulated the expression of Wnt/ßcatenin in OGD/Rstimulated HT22 cells. In conclusion, DMY protected HT22 cells from OGD/Rinduced oxidative stress and apoptosis, and its effects may be mediated by the activation of the Wnt/ßcatenin signaling pathway.
Assuntos
Glucose , Oxigênio , Apoptose , Sobrevivência Celular , Flavonóis/farmacologia , Glucose/metabolismo , Estresse Oxidativo , Oxigênio/metabolismo , Via de Sinalização WntRESUMO
Activated platelets (PLTs) participate in the regulation of tumor angiogenesis, and tumors can activate PLTs. Whether co-culture of lung carcinoma with PLTs improves the function of human umbilical vein endothelial cells (HUVECs) requires further investigation. The present study aimed to investigate the impact of H1975 cell crosstalk with PLTs on the proliferation, migration and tube formation of HUVECs. Following generation of cell-derived supernatants and construction of the co-culture system, Cell Counting Kit-8, flow cytometry, transmission electron microscopy and a meter for epithelial measurement were performed to detect the proliferative ability of HUVECs. Furthermore, the wound healing and Transwell migration assays were performed to detect the migratory ability of HUVECs. A tube formation assay was performed to assess angiogenesis, ELISA was applied to detect the content of vascular endothelial growth factor (VEGF) and western blotting was carried out to measure the expression levels of VEGF receptor 2 (VEGFR2) in HUVECs. Compared with single-cultured HUVECs (control), co-culture with H1975 cells and PLTs (Exp_HP) improved cell proliferation, increased the proportion of cells in the S-phase, destroyed the cell ultrastructure and decreased transepithelial electrical resistance in HUVECs. In addition, a higher relative migration rate, greater number of migrated cells, stronger tube-forming ability and increased expression of VEGF and VEGFR2 were detected in the Exp_HP group compared with the control group. The properties of HUVECs in Exp_H (co-cultured with H1975 cells) were similar to those in Exp_HP, but significantly weaker. Taken together, the results of the present study suggest that tumor cells interacting with PLTs may play an important role in tumor angiogenesis by affecting or mediating changes in the properties of vascular endothelial cells (VECs).
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Parkinson's disease (PD) is characterized by the loss of dopaminergic neurons in the substantia nigra and striatum. Aging is the most important risk factor of PD. Ferroptosis is an iron-dependent form of cell death associated with PD. However, it is not clear whether ferroptosis accelerates PD by promoting cellular senescence. This study investigated the mechanism of 1-methyl-4-phenylpyridinium (MPP+) -induced PC12 cells injury. We found that MPP+ induced cell senescence with increased ß-galactosidase activity and the expression of p53, p21 and p16 activation in cells. In addition, MPP+ treatment showed smaller mitochondria and increased membrane density, downregulation of ferritin heavy chain 1 expression and upregulation of acyl-CoA synthetase long chain family member 4 expression, and enhanced levels of oxidative stress, which were important characteristics of ferroptosis. Ferrostatin-1 (Fer-1), a ferroptosis inhibitor, was tested to eliminate MPP+-induced cell senescence. Fer-1 downregulated the expression of p53 and upregulated the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase-4 (GPX4) in MPP+-induced ferroptosis. Inhibition of p53 eliminated cell senescence by upregulation the expression of of SLC7A11 and GPX4. Thus, these results suggest that MPP+ induces senescence in PC12 cells via the p53/ SLC7A11/ GPX4 signaling pathway in the ferroptosis regulation mechanism.
Assuntos
1-Metil-4-fenilpiridínio/farmacologia , Senescência Celular/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Animais , Cicloexilaminas/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Fenilenodiaminas/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , beta-Galactosidase/metabolismoRESUMO
AIM: This study focused on the expression pattern of long non-coding RNA maternally expressed gene 3 (MEG3) and its value in ischemic stroke (IS). METHODS: The expression pattern and the roles of MEG3 in the development of IS were explored in mice IS model and human brain microvascular endothelial cells (hBMECs). A case-control study, including 215 IS patients and 153 controls, was also conducted to investigate its prognostic value. RESULTS: In vivo study showed that MEG3 increased significantly in the IS group (P=0.004), and its level remained stable within 3 to 48h after the onset of IS. Besides, the survival time of the mouse in the high MEG3 group was significantly lower than that in the low MEG3 group (P=0.042). In vitro study showed that oxygen-glucose deprivation (OGD) treatment significantly up-regulated expressions of MEG3, Bax, and cleaved caspase-3, and further promoted apoptosis of hBMECs, while si-MEG3 blocked these effects. A human study showed that MEG3 increased markedly within 48h of IS onset and was positively associated with the National Institutes of Health Stroke Scale (r=0.347, Pï¼0.001), modified Rankin Scale (r=0.385, Pï¼0.001), high-sensitivity C-reactive protein (r=0.221, P=0.002) level, and infarct volume (r=0.201, P=0.006). Overall survival analysis showed that patients with higher MEG3 expression within 48h had a relatively poor prognosis (Pï¼0.001). Meanwhile, multivariate analysis revealed that MEG3 was an independent prognostic marker for unfavorable functional outcome and death in IS patients. CONCLUSIONS: This study suggested that MEG3 might be considered as an intervention point and potential prognostic indicator for IS.
Assuntos
AVC Isquêmico , RNA Longo não Codificante , Idoso , Animais , Apoptose/genética , Proteínas Reguladoras de Apoptose/análise , Proteínas Reguladoras de Apoptose/genética , Estudos de Casos e Controles , China/epidemiologia , Modelos Animais de Doenças , Feminino , Estado Funcional , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , AVC Isquêmico/complicações , AVC Isquêmico/diagnóstico , AVC Isquêmico/genética , AVC Isquêmico/mortalidade , Masculino , Valor Preditivo dos Testes , Prognóstico , RNA Longo não Codificante/análise , RNA Longo não Codificante/genética , Índice de Gravidade de DoençaRESUMO
OBJECTIVE: The purpose of this paper was to study the protective effect of paeoniflorin on acute cerebral ischemia. The animal model of cerebral infarction induced by Middle Cerebral Artery Occlusion (MCAO) was blocked by the suture method. Sixty SD rats were randomly divided into the shame group, MCAO group, paeoniflorin (60, 120, 240 mg/kg, respectively) and Nimodipine (NMDP) group (n = 10 per group). METHODS: The rats were intragastrically administered immediately after the operation. After 7 days of gavage, the brains were decapitated at 24 h. Hematoxylin and Eosin (HE) staining was used to observe the degree of cell damage in the cerebral cortex of rats. Immunohistochemistry was used to detect silver plating and to observe changes in nerve cells. Rats in the model group showed obvious symptoms of neurological deficits, such as the ischemic morphological changed, the Malondialdehyde (MDA), Lactate Dehydrogenase (LD) content and lactate dehydrogenase (LDH) activity were significantly increased in the ischemic brain tissue, while the Superoxide Dismutase (SOD) activity was decreased. RESULTS: The decrease in Na+-K+-ATPase activity was significantly lower than that in the sham group. The neurological symptoms and signs of MCAO in the different doses of paeoniflorin group were improved, and the neuronal edema in the cortical area was alleviated. The activities of SOD, LDH and Na+-K+-ATPase were significantly increased, and the contents of MDA and LD were decreased. CONCLUSION: Therefore, paeoniflorin could alleviate the degree of tissue damage in rats with acute cerebral infarction, inhabit the formation of free radicals in the brain tissue after ischemia, and reduce the degree of lipid peroxidation. Thus, the degree of cell damage was reduced greatly and a protective effect was showed on cerebral ischemia.
Assuntos
Infarto Cerebral/prevenção & controle , Glucosídeos/farmacologia , Monoterpenos/farmacologia , Fármacos Neuroprotetores/farmacologia , Doença Aguda , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Infarto Cerebral/metabolismo , Infarto Cerebral/patologia , Modelos Animais de Doenças , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Nimodipina/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/prevenção & controle , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/metabolismoRESUMO
The underlying mechanisms of arterial remodeling (AR) remain unclear. Studies have indicated that decellularized scaffolds stimulate the differentiation of fibroblasts into myofibroblasts and promote the accumulation of the extracellular matrix (ECM). In the present study, the impact of ECM changes following AR on vascular smooth muscle cell (VSMC) phenotypes was investigated. VSMCs were co-cultured with normal or calcified decellularized arterial scaffolds. The expression levels of α-smooth muscle actin (α-SMA) and osteopontin (OPN) were measured at 2, 5, 10, 15 and 21 days following the establishment of the co-culture systems. The expression of α-SMA in the normal co-culture group was significantly increased compared with that in the calcified arterial decellularized scaffold co-culture group (P<0.05 and P<0.001). In addition, the expression of OPN in the AR co-culture group was significantly increased compared with the normal co-culture group (P<0.05 and P<0.001). To conclude, the calcified decellularized arterial scaffolds impact VSMC transformation by downregulating α-SMA expression and upregulating OPN expression (P<0.001). To the best of our knowledge, the present study is the first study that co-cultured VSMCs with normal or calcified decellularized arterial scaffolds.
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BACKGROUND: Bilirubin has been recognized as a potential endogenous inhibitor of atherosclerosis, being inversely associated with carotid intima-media thickness (CIMT). However, little information is available concerning the correlation between serum indirect bilirubin (IBIL), especially long-term IBIL level, and early atherosclerosis progression. This study was designed to evaluate the relationship between serum IBIL level and CIMT progression. METHODS: A total of 2205 participants were enrolled in this Asymptomatic Polyvascular Abnormalities Community study (APAC study). CIMT was measured at baseline and 2-year follow-up. The participants were divided into four groups based on their serum IBIL levels at baseline. Both baseline and average serum IBIL values during the 2-year follow up were used in the analysis. Multivariable logistic regression and linear regression were used to assess the associations between serum IBIL and CIMT progression. RESULTS: The results showed that 51.93% (1145/2205) of participants were diagnosed with CIMT progression during the 2-year follow-up. Baseline serum IBIL level was significantly associated with the incidence of CIMT progression after adjusting for other potential confounding factors. Compared with the first quartile, adjusted odds ratios (OR) of the second, third, and fourth quartiles of IBIL were 0.70 [95% confidence interval (CI), 0.55-0.90], 0.68 (95% CI, 0.52-0.87), and 0.63 (95% CI, 0.49-0.82) (P = 0.0006), respectively. Serum IBIL level during the follow-up was also associated with CIMT progression in the univariate analysis (P = 0.0022), although no longer significant after adjusting for potential confounders in the multiple linear regression. CONCLUSION: The study demonstrated the inverse relationship between serum IBIL and CIMT progression. Lower serum IBIL level is an independent predictor of subclinical atherosclerosis.
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Aterosclerose/diagnóstico por imagem , Bilirrubina/sangue , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Adulto , Idoso , Aterosclerose/sangue , Biomarcadores/sangue , Doenças das Artérias Carótidas/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , UltrassonografiaRESUMO
OBJECTIVE: To analyze the positive predictive value of large artery occlusion and clinical prognosis in acute ischemic stroke patients with total anterior circulation infarct (TACI) who underwent endovascular treatment in the absence of multimodal CT angiography or CT perfusion. METHODS: The inclusion criteria for the acute ischemic stroke patients to receive endovascular treatment were as the follows: the Oxfordshire Community Stroke Project classification was TACI, Alberta Stroke Program Early Computed Tomography Score (ASPECTS) ≥ 6, National Institutes of Health stroke scale (NIHSS) score ≥8, and less than 4.5 hours since stroke onset. The endovascular treatment was performed on patients who met the inclusion criteria. The endovascular treatment included intra-arterial thrombolysis, mechanical treatments, or both. A retrospective analysis was performed on all eligible acute ischemic stroke patients who underwent endovascular treatment from January 1, 2015 to December 31, 2015. RESULTS: A total of 17 patients met the inclusion criteria and underwent endovascular treatment. The median age was 76 years (range, 59-88 years). 12 patients (70.6%) were diagnosed with atrial fibrillation. 16 patients were diagnosed with large artery occlusion by digital subtraction angiography, and the positive predictive value was 94.1%. 16 patients (94.1%) had recanalization (TICI Grade 3); 12 patients (70.6%) had a modified Rankin Scale score of 0-2, and 1 patient (5.9%) died 90 days after treatment. CONCLUSIONS: In the absence of multimodal CT, endovascular treatment might be beneficial to patients with TACI acute ischemic stroke within 4.5 hours of stroke onset, who had NIHSS score of 8 or greater and ASPECTS of 6 or greater. These inclusion criteria have a high positive predictive value for anterior circulation large artery occlusion.
Assuntos
Infarto Encefálico/terapia , Procedimentos Endovasculares , Idoso , Idoso de 80 Anos ou mais , Infarto Encefálico/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Recent evidence suggests that pulse pressure (PP) is a strong cardiovascular diseases' risk factor. We systematically evaluated all relevant studies to determine whether PP can be used as an independent predictor of stroke and mortality. METHODS AND RESULTS: A meta-analysis was performed by searching the published literature using MEDLINE, Cochrane and Google Scholar databases up to December 15, 2015. We measured the effect size expressed by hazard ratio (HR) and 95 % confidence interval (95 % CI). Eleven publications were included in the analysis. Pooled results demonstrated that 10 mmHg increase in PP was associated with increased risk of stroke occurrence (pooled HR 1.046, 95 % CI 1.025-1.068, P < 0.001). Additionally, systolic blood pressure (SBP) (pooled HR 1.053, 95 % CI 1.033-1.073, P < 0.001) and diastolic blood pressure (DPB) (pooled HR 1.056, 95 % CI 1.038-1.074, P < 0.001) were found to be significant predictors for stroke. We did not find a significant association between PP and all-cause mortality (pooled HR 1.022, 95 % CI 0.983-1.063, P = 0.270). We found SBP (pooled HR 1.008, 95 % CI 1.002-1.014, P = 0.012), but not DBP (pooled HR 1.023, 95 % CI 0.964-1.085, P = 0.451) to be significantly associated with all-cause mortality. CONCLUSIONS: Current data confirms that PP is an independent risk factor for stroke but is not a predictor of mortality.
Assuntos
Pressão Sanguínea , Hipertensão/complicações , Acidente Vascular Cerebral/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Medição de Risco , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologiaRESUMO
OBJECTIVE: CHA2DS2-VASc is the extension of the CHADS2 score developed by Birmingham 2009. This risk stratification schema is often used in clinical setting when considering additional risk factors for developing stroke in AF patients. However, its role in the non-AF population is unknown. This study was designed to evaluate the accuracy of the CHADS2 and the CHA2DS2-VASc scoring systems. METHODS: Studies designed for CHADS2 and CHA2DS2-VASc score in stratifying the risks for stroke development in non-AF patients were included. RESULTS: Among the 114 studies identified, six trials were chosen finally and included for meta-analysis. The pooled diagnostic odds ratio (DOR) for CHADS2 and CHA2DS2-VASc was 2.86 (95% CI =1.83-4.28) and 2.80 (95% CI =1.83-4.28), respectively. CHA2DS2-VASc score was of better sensitivity than CHADS2 score (0.920 vs. 0.768). However, both scores were showed to have inherent heterogeneity and poor specificity. CONCLUSIONS: Though having good diagnostic accuracy, the clinical application of the CHADS2 and CHA2DS2-VASc scores in predicting risk of stroke development in non-AF patients still needs further validation. Key message The overall diagnostic accuracy of CHADS2 and CHA2DS2-VASc in stroke-risk stratification was good in patients with non-atrial fibrillation.
Assuntos
Fibrilação Atrial/complicações , Medição de Risco/métodos , Acidente Vascular Cerebral/epidemiologia , Tromboembolia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Técnicas de Apoio para a Decisão , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Acidente Vascular Cerebral/diagnóstico , Tromboembolia/diagnósticoRESUMO
The purpose of this study was to perform a meta-analysis of current literature to determine whether lowering blood pressure (BP) during the acute phase of an ischemic stroke improves short- and long-term outcomes. PubMed, Cochrane, and Embase were searched until September 5, 2014 using combinations of the search terms: blood pressure reduction, reduced blood pressure, lowering blood pressure, ischemic stroke, acute stroke, and intra-cerebral hemorrhage. Inclusion criteria were randomized controlled trial and patients with acute stroke (ischemic or hemorrhagic) treated with an antihypertensive agent or placebo. Outcome measures were change in systolic and diastolic BP (SBP, DBP) after treatment, and short- and long-term dependency and mortality rates. A total of 459 studies were identified, and ultimately 22 studies were included in the meta-analysis. The total number of participants in the treatment groups was 5672 (range, 6-2308), and in the control groups was 5416 (range, 6-2033). In most studies, more than 50% of the participants were males and the mean age was more than 60 years. The mean follow-up time ranged from 5 days to 12 months. As expected, treatment groups had a greater decrease in BP than control groups, and this effect was seen with different classes of antihypertensive drugs. Short-term and long-term dependency rates were similar between treatment and control groups (short-term dependency: pooled odds ratio [OR]â=â1.041, 95% confidence interval [CI]: 0.936-1.159, Pâ=â0.457; long-term dependency: pooled ORâ=â1.013, 95% CI: 0.915-1.120, Pâ=â0.806). Short-term or long-term mortality was similar between the treatment and control groups (short-term mortality: pooled ORâ=â1.020, 95% CI: 0.749-1.388, Pâ=â.902; long-term mortality: pooled ORâ=â1.039, 95% CI: 0.883-1.222, Pâ=â0.644). Antihypertensive agents effectively reduce BP during the acute phase of an ischemic stroke, but provide no benefit with respect to short- and long-term dependency and mortality.
Assuntos
Anti-Hipertensivos/uso terapêutico , Isquemia Encefálica/complicações , Isquemia Encefálica/mortalidade , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/mortalidade , Humanos , Prognóstico , Fatores de TempoRESUMO
OBJECTIVE: To summarize the use rate, safety, efficacy of antithrombotics in stroke/transient ischemic attack (TIA) prevention, and reasons for not using dabigatran etexilate (DE) in Shanghai, China. METHODS: Non-valvular atrial fibrillation (NVAF)-associated stroke patients were prospectively registered as an electronic database. Use rate of antithrombotics and reasons for not using DE were extracted during follow-up. Patients' baseline characteristics, recurrent ischemic stroke/TIA events and bleeding complications were analyzed. PATIENTS: From April 2012 to August 2014, 110 inpatients with NVAF-associated stroke were studied in our hospital. NVAF was diagnosed by 12-lead electrocardiogram, 24 h Holter and echocardiography. RESULTS: Before introduction of DE (April 2013), use rates of warfarin and antiplatelets were 28.9% (11/38) and 60.5% (23/38) respectively; after that, use rates of warfarin, DE, and antiplatelets were 20.8% (15/72), 12.5% (9/72), and 43.1% (31/72). The DE did not improve use of anticoagulants (P = 0.639). There were 19 (17.3%) recurrent ischemic stroke events up to October 2015; two (9.5%) in the non-user group, 10 (18.5%) in the antiplatelet group, and seven (20.0%) in the anticoagulants group (P = 0.570). Furthermore, recurrence rates were similar between the DE group (20.0%) and the Warfarin group (20.0%, P = 1.000). The most common reason for not using DE was financial concerns (61.0%), followed by inconvenience to purchase (14.0%) and hemorrhage concerns (11.0%). Two patients using warfarin found fecal occult blood so they stopped warfarin and began to use antiplatelet drugs. No bleeding event occurred in the other groups. Only one patient had side effects (dyspepsia and gastroesophageal reflux) from DE. CONCLUSION: The use rate of either DE or warfarin in Shanghai was low; DE had not improved anticoagulation therapy for NVAF patients in Shanghai mainly because DE had not been covered by health insurance.