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The effects of long non-coding RNAs (lncRNAs) on cellular biological processes and even the tumorigenesis have been widely reported. Small nucleolar RNA host gene 6 (SNHG6) has been reported to participate in regulating biological behaviors of multiple types of cancers. Nevertheless, the functions of SNHG6 in osteosarcoma still remain to be uncovered. This study intended to determine the clinical significance and biological functions of SNHG6 in osteosarcoma. It was confirmed by qRT-PCR that SNHG6 was highly expressed in osteosarcoma tissues and cell lines. Highly expressed SNHG6 predicted poor survival rate and advanced clinical stage for osteosarcoma patients, according to Kaplan-Meier method and Cox regression analysis. Loss-of-function assays were performed to examine the effects of silenced SNHG6 on the progression of osteosarcoma, indicating that silenced SNHG6 suppressed cell proliferation through inducing cell cycle arrest in G0/G1 phase and causing cell apoptosis. In vitro assays exposed the potential oncogenic role of SNHG6 in osteosarcoma, further affirmed by in vivo nude mice assays. Mechanistic assays demonstrated that SNHG6 was negatively correlated with p21 and KLF2 in osteosarcoma. And biological functions of SNHG6 in osteosarcoma were realized through regulating p21 and KLF2. Collectively, SNHG6 was a new type of molecule involving in the progression of osteosarcoma.
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Neoplasias Óseas/diagnóstico , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Factores de Transcripción de Tipo Kruppel/genética , Osteosarcoma/diagnóstico , ARN Largo no Codificante/genética , Adulto , Animales , Apoptosis/genética , Neoplasias Óseas/genética , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Puntos de Control de la Fase G1 del Ciclo Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Ratones Desnudos , Osteosarcoma/genética , Pronóstico , Regulación hacia Arriba , Adulto JovenRESUMEN
BACKGROUND: Porcine reproductive and respiratory syndrome virus (PRRSV) causes porcine reproductive and respiratory syndrome (PRRS), which is currently insufficiently controlled. From a previous small-scale screen we identified an effective DNA-based short antisense oligonucleotide (AS-ON) targeting viral NSP9, which could inhibit PRRSV replication in both Marc-145 cells and pulmonary alveolar macrophages (PAMs). The objective of this study was to explore the strategy of incorporating locked nucleic acids (LNAs) to achieve better inhibition of PRRSV replication in vitro. METHODS: The effective DNA-based AS-ON (YN8) was modified with LNAs at both ends as gap-mer (LNA-YN8-A) or as mix-mer (LNA-YN8-B). Marc-145 cells or PAMs were infected with PRRSV and subsequently transfected. RESULTS: Compared with the DNA-based YN8 control, the two AS-ONs modified with LNAs were found to be significantly more effective in decreasing the cytopathic effect (CPE) induced by PRRSV and thus in maintaining cell viability. LNA modifications conferred longer lifetimes to the AS-ON in the cell culture model. Viral ORF7 levels were more significantly reduced at both RNA and protein levels as shown by quantitative PCR, western blot and indirect immunofluorescence staining. Moreover, transfection with LNA modified AS-ON reduced the PRRSV titer by 10-fold compared with the YN8 control. CONCLUSION: Taken together, incorporation of LNA into AS-ON technology holds higher therapeutic promise for PRRS control.
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Ácidos Nucleicos/química , Oligonucleótidos Antisentido/farmacología , Virus del Síndrome Respiratorio y Reproductivo Porcino/efectos de los fármacos , Replicación Viral/efectos de los fármacos , Animales , Western Blotting/veterinaria , Línea Celular , Chlorocebus aethiops , Técnica del Anticuerpo Fluorescente Indirecta/veterinaria , Técnicas In Vitro , Riñón/citología , Riñón/virología , Macrófagos Alveolares/virología , Ácidos Nucleicos/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , ARN Viral/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinariaRESUMEN
OBJECTIVE: We aimed to investigate the expression characteristics of transient receptor potential canonical 7 (TRPC7) in normal and hypertrophic cardiac myocytes. METHODS: The 2-kidney 1-clip (2K1C) method was used to induce renovascular hypertension. Losartan, the potent inhibitor of angiotensin II (Ang II) receptor, was applied to the drinking water of 2K1C rats to inhibit Ang II-mediated responses. TRPC7 expression was examined by immunohisto/cytochemistry and Western blot analyses in normal and hypertrophic hearts. The expression level of protein kinase C (PKC), a negative regulator of TRPC7 channel in in vitro study, was also evaluated. RESULTS: In normal rat ventricles, strong TRPC7 immunoreactivity was distributed in the surface sarcolemma of cardiomyocytes, and a moderate but striated TRPC7 immunoreactivity was also detected in the subcellular regions. The 2K1C operation caused significant hypertension and cardiac hypertrophy as demonstrated by respective biophysical or biochemical assays. At this stage, expression of TRPC7 was significantly downregulated at both tissue and cell levels, whereas that of PKC was upregulated. Further analysis revealed a negative correlation between TRPC7 and PKC expression patterns. Oral application of losartan ameliorated the extent of experimentally induced hypertension and cardiac hypertrophy. Simultaneously, it effectively reversed the downregulation of TRPC7 and mildly antagonized the upregulation of PKC. CONCLUSIONS: Taken together, these results for the first time show that TRPC7 localizes in the surface and tubular sarcolemma of cardiomyocytes in normal adult rats and its expression significantly decreases in hypertrophied cardiomyocytes from renovascular hypertensive rats. TRPC7 may thus play a significant role in normal physiological settings in the heart.
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BACKGROUND: Porcine reproductive and respiratory syndrome (PRRS) is caused by porcine reproductive and respiratory syndrome virus (PRRSV) and is an economically important disease in swine-producing areas. The objective of this study was to screen for effective antisense oligonucleotides (AS-ONs) which could inhibit PRRSV replication in MARC-145 cells and in pulmonary alveolar macrophages (PAM). RESULTS: Nine short AS-ON sequences against the well-conserved regions of PRRSV (5'-UTR, NSP9, ORF5 and ORF7) were selected. When MARC-145 cells or PAM were infected with PRRSV followed by transfection with AS-ONs, four AS-ON sequences targeting 5'-UTR, ORF5 or NSP9 were found to be the most effective oligonucleotides in decreasing the cytopathic effect (CPE) induced by PRRSV infection. Quantitative PCR and indirect immunofluorescence staining confirmed that ORF7 levels were significantly reduced both at RNA and protein levels. The PRRSV titration data furthermore indicated that transfection with AS-ON YN8 could reduce the PRRSV titer by 1000-fold compared with controls. CONCLUSION: The results presented here indicate that DNA-based antisense oligonucleotides can effectively inhibit PRRSV replication in MARC-145 cells and in PAM. Furthermore, comparing with the reported hit rates (approximately 10-30 %), we achieved a higher success rate (44 %). The strategy we took to design the antisense sequences might be applied to select AS-ONs that more efficiently reduce the expression of target genes.
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Oligorribonucleótidos Antisentido/fisiología , Virus del Síndrome Respiratorio y Reproductivo Porcino/fisiología , Animales , Antivirales/farmacología , Línea Celular , Silenciador del Gen , Haplorrinos , Macrófagos/virología , Alveolos Pulmonares/citología , ARN Viral , Porcinos , Replicación ViralRESUMEN
The recombinant plasmid pCI-IL-4-IL-2-EGFP containing fusion genes of chicken IL-4 and IL-2 can be used as an adjuvant to enhance the anticoccidiosis effect of the chicken coccidia live vaccine. The chickens were divided into 3 groups: blank control group, vaccine + pCI-IL-4-IL-2-EGFP adjuvant coimmunization group, and vaccine-only group to investigate the immune synergy mechanism of recombinant plasmid adjuvant pCI-IL-4-IL-2-EGFP. The expressions of IL-2, IL-4, TNF-α, and IFN-γ in chicken sera and tissues were detected by ELISA and RT-qPCR, and the proliferation of T and B lymphocytes and antigen presenting cells (APC) in chicken immune organs and intestines were detected by acid alpha-naphthalase (ANAE) staining, methyl green pyronine (MGP) staining, and immunofluorescence (IF) staining, respectively. Results showed that the mRNA expression of IL-2, IL-4, IFN-γ and the number of activated T and B lymphocytes were significantly upregulated in the spleen and cecum tonsils of chickens in vaccine + pCI-IL-4-IL-2-EGFP group compared with the vaccine-only group on 7 d after vaccination (P < 0.05). Protein contents of IL-2, IL-4 and TNF-α in vaccine + pCI-IL-4-IL-2-EGFP group were significantly increased compared to vaccine-only group on 28 d of inoculation (P < 0.05). The number of T and B lymphocytes and APC in chickens of the vaccine+ pCI-IL-4-IL-2-EGFP group was significantly higher than that of the vaccine-only group in cecum tonsils, thymus and spleen after 14 and 28 d of inoculation (P < 0.05). All results revealed that pCI-IL-4-IL-2-EGFP adjuvant enhanced the immune response of chicken coccidia live vaccine by upregulating the expression of IL-2, IL-4, TNF-α, and IFN-γ and promoting the proliferation of T, B lymphocytes and APCs in chicken intestines and immune organ sites. Moreover, our study provides a theoretical basis for the clinical application of cytogenic plasmids as adjuvants.
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Pollos , Coccidios , Animales , Pollos/genética , Interleucina-2/genética , Interleucina-4/genética , Factor de Necrosis Tumoral alfa/genética , Coccidios/genética , Coccidios/metabolismo , Adyuvantes Inmunológicos , Plásmidos/genéticaRESUMEN
Intestinal mucosa injury and loss of weight gain are unavoidable while using live vaccine strain to prevent chicken coccidiosis. In this study, recombinant Lactococcus lactis NZ3900/pNZ8149-IL-4-IL-2, expressing the fusion protein of chicken IL-4 and IL-2, was constructed using food-grade NICE expression system, trying to develop a possible oral immune adjuvant to enhance the immune effect of the live vaccine against chicken coccidiosis and minimize its adverse effects. Chickens were given different doses of recombinant L. lactis together with the live vaccine, then experimently attacked with coccidia virulent strains. Results showed that weight gains of co-immunization groups, given both 1 × 109 or 1 × 1010 CFU recombinant L. lactis and the live vaccine, were significantly higher than the vaccine-only group (P<0.05), while intestinal lesion scores of duodenum, jejunum, and cecum were significantly lower than the vaccine-only group (P<0.05), so was the oocyst shedding. The anticoccidial indexes (ACI) of the co-immunized groups given 1 × 109 and 1 × 1010 CFU recombinant L. lactis were 187.85 and 193.33, respectively, higher than 174.61 of the vaccine-only group. In addition, chickens in co-immunization groups gained more body weight than the vaccine-only group before being challenged with the virulent strains (P<0.05). All the results indicated that the constructed recombinant L. lactis NZ3900/ pNZ8149-IL-4-IL-2 exhibited an immune synergistic function to coccidiosis live vaccine, and could alleviate its adverse effect affecting weight gain. The application of the recombinant L. lactis showed the potency to lift the anticoccidial efficiency of the live vaccine from a medium level to a high level.
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Coccidios , Coccidiosis , Lactococcus lactis , Enfermedades de las Aves de Corral , Animales , Pollos , Interleucina-4/metabolismo , Lactococcus lactis/genética , Lactococcus lactis/metabolismo , Interleucina-2 , Coccidiosis/prevención & control , Coccidiosis/veterinaria , Aumento de Peso , Enfermedades de las Aves de Corral/prevención & controlRESUMEN
OBJECTIVES: 20-hydroxyeicosatetraenoic acid (20-HETE) is a metabolite of arachidonic acid catalysed by cytochrome P450 enzymes and plays an important role in cell death and proliferation. We hypothesized that 20-HETE synthesis inhibition may have protective effects in traumatic brain injury (TBI) and investigated possible underlying molecular mechanisms. MATERIALS AND METHODS: Neurologic deficits, and lesion volume, reactive oxygen species (ROS) levels and cell death as assessed using immunofluorescence staining, transmission electron microscopy and Western blotting were used to determine post-TBI effects of HET0016, an inhibitor of 20-HETE synthesis, and their underlying mechanisms. RESULTS: The level of 20-HETE was found to be increased significantly after TBI in mice. 20-HETE synthesis inhibition reduced neuronal apoptosis, ROS production and damage to mitochondrial structures after TBI. Mechanistically, HET0016 decreased the Drp1 level and increased the expression of Mfn1 and Mfn2 after TBI, indicating a reversal of the abnormal post-TBI mitochondrial dynamics. HET0016 also promoted the restoration of SIRT1 and PGC-1α in vivo, and a SIRT1 activator (SRT1720) reversed the downregulation of SIRT1 and PGC-1α and the abnormal mitochondrial dynamics induced by 20-HETE in vitro. Furthermore, plasma 20-HETE levels were found to be higher in TBI patients with unfavourable neurological outcomes and were correlated with the GOS score. CONCLUSIONS: The inhibition of 20-HETE synthesis represents a novel strategy to mitigate TBI-induced mitochondrial dysfunction and neuronal apoptosis by regulating the SIRT1/PGC-1α pathway.
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Amidinas/farmacología , Apoptosis/efectos de los fármacos , Lesiones Traumáticas del Encéfalo/patología , Ácidos Hidroxieicosatetraenoicos/metabolismo , Dinámicas Mitocondriales/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Animales , Lesiones Traumáticas del Encéfalo/veterinaria , Dinaminas/metabolismo , Femenino , Humanos , Ácidos Hidroxieicosatetraenoicos/sangre , Ácidos Hidroxieicosatetraenoicos/farmacología , Modelos Logísticos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Mitocondrias/metabolismo , Mitocondrias/ultraestructura , Neuronas/citología , Neuronas/metabolismo , Neuronas/ultraestructura , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Sirtuina 1/química , Sirtuina 1/metabolismoRESUMEN
BACKGROUND: To compare the long-term therapeutic effects of stereotactic aspiration (SA), endoscopic evacuation (EE), and open craniotomy (OC) in the surgical treatment of spontaneous basal ganglia hemorrhage and explore the appropriate clinical indications for each technique. METHODS: Multiple-treatment inverse probability of treatment weighting (IPTW)-adjusted logistic regression analysis was performed to evaluate the therapeutic effects of these techniques. The primary and secondary outcomes were 6-month modified Rankin Scale (mRS) and mortality rates, respectively. RESULTS: A total of 703 patients were ultimately enrolled. For the entire cohort, the 6-month mortality rate was significantly higher (OR 2.396, 95% CI: 1.865-3.080), and the 6-month functional outcome was significantly worse (OR 1.359, 95% CI: 1.091-1.692) for SA than that of EE. The 6-month mortality rate for OC was significantly higher (OR 1.395, 95% CI: 1.059-1.837) than that of EE. Further subgroup analysis was stratified by initial hematoma volume and Glasgow Coma Scale (GCS) score. The mortality rate for SA was significantly higher for patients with hematoma volume of 20-40 mL (OR 6.226, 95% CI: 3.848-10.075), 40-80 mL (OR 2.121, 95% CI: 1.492-3.016), and ≥80 mL (OR 5.544, 95% CI: 3.315-9.269) than in the same subgroups of EE. The functional outcomes for SA were significantly worse than that of EE for hematoma volume subgroups of 40-80 mL (OR 1.424, 95% CI: 1.039-1.951) and ≥80 mL (OR 4.224, 95% CI: 1.655-10.776). The mortality rate for SA was significantly higher than that of EE for the GCS score subgroups of 6-8 (OR 2.082, 95% CI: 1.410-3.076) and 3-5 (OR 2.985, 95% CI: 1.904-4.678). The mortality rate for OC was significantly higher for the GCS score of 3-5 subgroup (OR 1.718, 95% CI: 1.115-2.648), and a tendency for a higher mortality rate of 6-8 subgroup (OR 1.442, 95% CI: 0.965-2.156) than that of EE. CONCLUSIONS: EE can decrease the 6-month mortality rate and improve the 6-month functional outcomes of spontaneous basal ganglia hemorrhage in patients with a hematoma volume ≥40 mL. EE can decrease the 6-month mortality rate of spontaneous basal ganglia hemorrhage in patients with a GCS score of 3-8.
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Background: Carotid angioplasty stenting (CAS) is a currently widely used surgical treatment of carotid artery stenosis. However, the influences of the perioperative blood pressure (BP) on patients' prognosis remain unclear. Objective: The present study was designed to explore the effects of different perioperative BP control strategies on CAS patients' prognosis. Methods: One hundred seventy-three consecutive patients admitted between January 2016 and April 2019 were reviewed retrospectively. The outcomes of patients with different systolic BP (<120, 120-130, and >130 mmHg) before CAS and within 24 h after CAS were compared. The primary outcomes were the incidence of secondary cerebral infarction (CI) and intracranial hemorrhage (ICH) after CAS. The secondary outcome was the incidence of unfavorable discharge and in-hospital death. The unfavorable discharge was defined as modified Rankin Scale (mRS) score 3-5 at discharge. Results: There was no significant difference between the incidences of ICH (P = 0.803) and CI (P = 0.410) in patients with different BP before CAS. The patients with post-CAS BP values of >130 mmHg had a 37.67-fold increased risk (95% CI: 6.79-209.01) of ICH compared with others, while no significant difference was observed on the incidence of CI (P = 0.174) among patients with different post-CAS BP values. The patients with post-CAS BP values of >130 mmHg also had a significantly higher incidence of unfavorable discharge (P = 0.002) and in-hospital death (P = 0.001) compared with others. Conclusion: High BP (>130 mmHg) within 24 h after CAS significantly increases the risks of secondary cerebral hemorrhage, unfavorable discharge, and in-hospital death. Thus, the BP should be controlled below 130 mmHg in the first 24 h after CAS.
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Clinical advances in the treatment of intracranial hemorrhage (ICH) are restricted by the incomplete understanding of the molecular mechanisms contributing to secondary brain injury. Acrolein is a highly active unsaturated aldehyde which has been implicated in many nervous system diseases. Our results indicated a significant increase in the level of acrolein after ICH in mouse brain. In primary neurons, acrolein induced an increase in mitochondrial fragmentation, loss of mitochondrial membrane potential, generation of reactive oxidative species, and release of mitochondrial cytochrome c. Mechanistically, acrolein facilitated the translocation of dynamin-related protein1 (Drp1) from the cytoplasm onto the mitochondrial membrane and led to excessive mitochondrial fission. Further studies found that treatment with hydralazine (an acrolein scavenger) significantly reversed Drp1 translocation and the morphological damage of mitochondria after ICH. In parallel, the neural apoptosis, brain edema, and neurological functional deficits induced by ICH were also remarkably alleviated. In conclusion, our results identify acrolein as an important contributor to the secondary brain injury following ICH. Meanwhile, we uncovered a novel mechanism by which Drp1-mediated mitochondrial oxidative damage is involved in acrolein-induced brain injury.
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Acroleína , Lesiones Encefálicas , Hemorragia Cerebral , Dinaminas/metabolismo , Mitocondrias , Estrés Oxidativo , Acroleína/metabolismo , Animales , Apoptosis , Lesiones Encefálicas/patología , Hemorragia Cerebral/patología , Masculino , Ratones , Ratones Endogámicos C57BLRESUMEN
Aims: The surgical evacuation, including stereotactic aspiration, endoscopic evacuation, and craniotomy, is the most effective way to reduce the volume of intracerebral hemorrhage. However, credible evidence for the effects of these techniques is still insufficient. The present study explored the long-term outcomes of these techniques in the treatment of basal ganglia hematoma with low Glasgow Coma Scale (GCS) scores (≤8) and large-volume (≥40 ml), which were predictors of high mortality. Methods: Two hundred and fifty-eight consecutive patients were reviewed retrospectively. The primary and secondary outcomes were 6-months mortality and 6-months modified Rankin Scale score, which were assessed by a multivariate logistic regression model. Results: Compared with the endoscopic evacuation group, the mortality was significantly higher in the stereotactic aspiration group (OR 6.858, 95% CI 3.146-14.953) and open craniotomy group (OR 3.315, 95% CI 1.497-7.341). Age (OR = 2.237, 95% CI 1.290-3.877) and herniation (OR = 2.257, 95% CI 1.172-4.348) were independent predictors for mortality. No significant difference in the neurological functional outcome was found in the stereotactic aspiration group (OR 0.501, 95% CI 0.192-1.308) and the craniotomy group (OR 0.774, 95% CI 0.257-2.335) compared with the endoscopic evacuation group. Conclusion: Endoscopic evacuation significantly decreased the 6-months mortality in patients with hemorrhage ≥40 ml and GCS ≤ 8.
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Long noncoding RNAs (lncRNAs) have been reported to participate in tumorigenesis and diverse cellular processes in osteosarcoma (OS). However, the role of lncRNA LINC00152 in OS remains elusive. In this study, LINC00152 was highly expressed in osteosarcoma tissues and cell lines. Moreover, MTT and colony formation assays revealed that knockdown of LINC00152 significantly suppressed cell proliferation. The inhibitory effect of LINC00152 knockdown on OS cell migration and invasion was analyzed and demonstrated by transwell assays. Additionally, Chromatin immunoprecipitation (ChIP) and luciferase reporter assays suggested that LINC00152 was transcriptionally activated by the transcription factor TCF3. More importantly, mechanism investigation revealed that LINC00152 was predominantly located in the cytoplasm of OS cells and acted as a competing endogenous RNA (ceRNA) in OS by regulating miR-1182/CDK14 axis. Collectively, LINC00152 was activated by TCF3 and promotes cell proliferation and migration in osteosarcoma via miR-1182-CDK14 axis.
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Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Neoplasias Óseas/patología , Regulación Neoplásica de la Expresión Génica/genética , Osteosarcoma/patología , ARN Largo no Codificante/genética , Adulto , Anciano , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Neoplasias Óseas/genética , Carcinogénesis/genética , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Quinasas Ciclina-Dependientes/genética , Quinasas Ciclina-Dependientes/metabolismo , Femenino , Humanos , Masculino , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Osteosarcoma/genéticaRESUMEN
The present study aims to investigate the similarities and differences between the host cells apoptosis induced by virulent line of Eimeria tenella (Tsx) and precocious line (PTsx), which can provide a theoretical basis for the study of drugs and vaccines against coccidiosis. HE staining, Hoechst 33342/AnnexinV-FITC/PI composite staining, and ELISA were used to detect the infection rate, apoptosis rate, and Caspase-3 enzyme activity of host cells infected by PTsx or Tsx, respectively. The apoptotic rates and Caspase-3 absorbance of the inoculation groups were lower (P < 0.05 or P < 0.01) than those of the control group at 4 h, whereas the apoptotic rates and Caspase-3 absorbance of the inoculation groups were higher (P < 0.05 or P < 0.01) than those of the control groups at 24 to 120 h. At the same inoculation dose, there was no significant difference in the infection rate, apoptosis rate or Caspase-3 absorbance between Tsx groups and PTsx groups after E. tenella inoculation for 4 to 72 h (P > 0.05). However, these indicators of PTsx groups were lower (P < 0.01) than those of the same dose inoculated Tsx groups at 120 h. The apoptosis rates of cecal and glandular epithelial cells in the inoculated groups were higher (P < 0.01) than those in the control group after inoculated E. tenella 5 D in vivo, and the apoptosis rates of cecal and glandular epithelial cells in PTsx group was lower (P < 0.01) than that in the same dose inoculated Tsx group. These observations indicate that both Tsx and PTsx inhibit host cell apoptosis in the early development of E. tenella, induce host cell apoptosis in the middle and late stages, and the apoptosis-inducing effect on host cells increases with increasing dose. However, when the same dose of oocysts was inoculated, the amount of apoptosis induced by PTsx in late development was less than Tsx.
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Apoptosis , Pollos , Coccidiosis/veterinaria , Eimeria tenella/fisiología , Enfermedades de las Aves de Corral/inmunología , Animales , Coccidiosis/inmunología , Coccidiosis/parasitología , Enfermedades de las Aves de Corral/parasitologíaRESUMEN
Ischemic stroke is a severe cerebrovascular disease. Although great progress has been made, the consequent ischemia-reperfusion (I/R) injury is inevitable and affects the therapeutic effect. Adiponectin (APN) is a fat-derived plasma protein that has beneficial actions on cardiovascular disorders. The present study aims to investigate the effect of APN on I/R injury and the potential underlying mechanisms. In step 1, APN were administered for three times (once every 8 h) 24 h before middle cerebral artery occlusion (MCAO). The results indicated that APN treatment reduced infarct volume, neurological deficits and brain water content after I/R injury. Meanwhile, APN was proved to increase the expression of cAMP, PKA, CREB, and BDNF. In step 2, mice were randomly assigned into the Vehicle + I/R, APN + I/R, PKA activator + I/R, PKA inhibitor + APN + I/R groups. PKA activator, PKA inhibitor, as well as APN were administered for three times before MCAO. The results indicated that PKA inhibitor downregulated the expressions of cAMP, PKA, CREB, and BDNF which subsequently weakened the protective effects of APN on cerebral I/R injury. In conclusion, our findings further suggest that APN exerts protective effect against cerebral I/R injury might through the cAMP/PKA-CREB-BDNF signaling pathway. APN is a novel candidate in the treatment of I/R diseases in the future.
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Adiponectina/farmacología , Isquemia Encefálica/tratamiento farmacológico , Daño por Reperfusión/tratamiento farmacológico , Animales , Isquemia Encefálica/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , AMP Cíclico/metabolismo , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Neuroprotección , Daño por Reperfusión/metabolismo , Transducción de Señal/efectos de los fármacos , Accidente Cerebrovascular/metabolismoRESUMEN
Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke, which leads to a high rate of mortality and poor neurological outcomes worldwide. Thrombolytic evacuation with urokinase-type plasminogen activator (uPA) or tissue-type plasminogen activator (tPA) has been showed to be a hopeful treatment for ICH. However, to the best of our knowledge, no clinical trials were reported to compare the efficacy and safety of these two fibrinolytics administrated following minimally invasive stereotactic puncture (MISP) in patients with spontaneous basal ganglia ICH. Therefore, the authors intended here to evaluate the differential impact of uPA and tPA in a retrospective study. In the present study, a total of 86 patients with spontaneous ICH in basal ganglia using MISP received either uPA (uPA group, n = 45) or tPA (tPA group, n = 41), respectively. The clinical baseline characteristics prior to the operation were collected. In addition, therapeutic responses were assessed by the short-term outcomes within 30 days postoperation, as well as long-term outcomes at 1 year postoperation. Our findings showed that, in comparison with tPA, uPA was able to better promote hematoma evacuation and ameliorate perihematomal edema, but the differences were not statistically significant. Moreover, the long-term functional outcomes of both groups were similar, with no statistical difference. In conclusion, these results provide evidence supporting that uPA and tPA are similar in the efficacy and safety for thrombolytic evacuation in combination with MISP in patients with spontaneous basal ganglia ICH.
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Hepatoma-derived growth factor (HDGF) regulates various cellular processes involved in the onset and development of tumors. To evaluate the role of HDGF in human gliomas, western blotting analysis, immunohistochemistry staining and reverse transcription-quantitative polymerase chain reaction were performed to detect HDGF protein and mRNA expression levels in glioma and intractable epileptic brain tissue. Various clinicopathological characteristics, including age, gender, World health Organization grade, HDGF expression level, Karnofsky performance Status (KPS) and Ki-67 index were obtained from medical records. The correlation between HDGF expression and these clinicopathological characteristics was statistically evaluated. Following this, multivariate liner regression was used to evaluate their effect on patient survival time. HDGF expression, at the protein and mRNA levels, was observed to be more upregulated in glioma tissues compared with intractable epileptic brain tissue without tumor. Furthermore, the level of HDGF expression was positively associated with the grade of malignancy [grades II~IV, Ki-67 index ≥20% or KPS <80 (P<0.05)] and poor prognosis in glioma patients. Notably, the univariate survival analysis identified a negative correlation between HDGF-expression and survival time (P<0.01) and multivariate liner regression demonstrated that HDGF expression is an independent prognostic factor for gliomas (P=0.01). Overall, HDGF upregulation may be a crucial step in the development and invasion of glioma. Further survival analysis highlighted its prognostic value for this malignancy, implying its potential as a promising therapeutic target for gliomas.
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Inflammatory markers have been associated with functional outcome and mortality of stroke. We investigated the changes in procalcitonin (PCT) and high-sensitivity C-reactive protein (Hs-CRP) levels during the acute period of ischemic stroke and evaluated the relationship between these levels and the long-term functional outcome and mortality. We prospectively studied 376 patients with acute ischemic stroke (AIS) who were admitted within 24 h after the onset of symptoms. PCT, Hs-CRP, and NIH Stroke Scale (NIHSS) were measured at the time of admission. Long-term functional outcome were measured by modified Rankin scale (mRS) at 1 year after admission. The correlations between the levels of PCT, Hs-CRP, and mortality at 1 year after stroke onset were analyzed. Patients with poor with functional outcome and non-survivors had significantly increased PCT and Hs-CRP levels on admission. Multivariate logistic regression analysis showed that PCT was an independent prognostic marker of 1-year functional outcome and death [odds ratio (OR) 2.33 (95% CI, 1.33-3.44) and 3.11 (2.02-4.43), respectively, P < 0.0001 for both, adjusted for age, NIHSS, other predictors, and vascular risk factors] in patients with AIS. The area under the receiver operating characteristic curve of PCT was 0.77 (95% CI, 0.72-0.83) for functional outcome and 0.88 (95% CI, 0.84-0.93) for mortality. PCT improved the area under the receiver operating characteristic curve of the NIHSS score for functional outcome from 0.74 (95% CI, 0.66-0.81) to 0.85 (95% CI, 0.76-0.92; P < 0.0001) and for mortality from 0.77 (95% CI, 0.70-0.83) to 0.94 (95% CI, 0.89-0.97; P < 0.0001). Serum level of PCT at admission was an independent predictor of long-term functional outcome and mortality after ischemic stroke in Chinese sample.
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Isquemia Encefálica/sangre , Proteína C-Reactiva/análisis , Calcitonina/sangre , Anciano , Área Bajo la Curva , Biomarcadores , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/mortalidad , Imagen de Difusión por Resonancia Magnética , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Curva ROC , Factores de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Microglia activation plays an important role in neuroinflammation. Sirtuin1 (SIRT1) has been shown to play a role in regulation of inflammation. Resveratrol, a potent SIRT1 activator, has anti-inflammation property. MicroRNA (miRNA or miR) related to inflammation pathways has been shown to be a promising therapeutic approach for septic encephalopathy (SE). The miR mediated mechanism of regulation of SIRT1 expression in encephalitis. However, the mechanism of was unknown. To address this question, we investigated whether miRNAs and resveratrol regulate the SIRT1 and the functional changes of mice microglia cell lines pre-treated with or without lipopolysaccharide (LPS). The research about direct role of miR-204 and resveratrol on expression of SIRT1 in mice microglia cell lines (N9 and BV2) pre-treated with or without LPS had been performed. Mice microglia cell lines were transfected with miR-204 mimics and inhibitors or treated with resveratrol, and the effects on cell growth, proliferation, and apoptosis of cells were assessed. LPS induced inflammation and activation of mice microglia. Through overexpression of SIRT1, resveratrol, and inhibitor of miR-204 inhibited inflammation process, proliferation of mice microglia cells and promoted its apoptosis. We identified if resveratrol and miR-204 could repress inflammation process and proliferation of mice microglia cell through promoting the expression of SIRT1.