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Objective: To investigate the effect of serine/arginine-rich splicing factor 2 (SRSF2) on ferroptosis and its possible mechanism in glioblastoma cells. Methods: The online database of gene expression profiling interactive analysis 2 (GEPIA 2) and Chinese Glioma Genome Atlas were used to analyze the expression of SRSF2 in glioblastoma tissue and its association with patients prognosis. To validate the findings of the online databases, the pathological sections of glioblastoma and non-tumor brain tissues from Tianjin Medical University General Hospital, Tianjin, China were collected and analyzed by using immunohistochemistry. Silencing SRSF2 gene expression in glioblastoma cells by siRNA was analyzed with Western blot. The proliferation index was detected by using CCK8 assay. The rescued experiment was conducted by using expression plasmid of pcDNA3.1(+)-SRSF2. The activity of ferroptosis was assessed by using the levels of iron ions and malondialdehyde in glioblastoma cells and the changes in the ratio of glutathione to oxidized glutathione. The changes of gene expression and differential pre-mRNA alternative splicing (PMAS) induced by SRSF2 were monitored by using the third-generation sequencing technology analysis, namely Oxford nanopore technologies (ONT) sequencing analysis. Results: SRSF2 expression was higher in glioblastoma tissues than non-tumor brain tissues. Immunohistochemistry also showed a positive rate of 88.48%±4.60% in glioblastoma tissue which was much higher than the 9.97%±4.57% in non-tumor brain tissue. The expression of SRSF2 was inversely correlated with overall and disease-free disease survivals (P<0.01). The proliferation index of glioblastoma cells was significantly reduced by silencing with SRSF2 siRNA (P<0.01) and could be reversed with transfection of exogenous SRSF2. The levels of intracellulariron ions and malondialdehyde increased (P<0.05), but the glutathione/oxidized glutathione ratio and the expression of key proteins in the glutathione pathway remained unchanged (P>0.05). ONT sequencing results showed that silencing SRSF2 in glioblastoma cells could induce a significant alternative 3' splice site change on ferroptosis suppressor protein 1 (FSP1). Conclusion: SRSF2 inhibits the ferroptosis in glioblastoma cells and promotes their proliferation, which may be achieved by regulating FSP1 PMAS.
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Empalme Alternativo , Neoplasias Encefálicas , Proliferación Celular , Ferritinas , Ferroptosis , Glioblastoma , Oxidorreductasas , Factores de Empalme Serina-Arginina , Humanos , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Ferroptosis/genética , Regulación Neoplásica de la Expresión Génica , Glioblastoma/genética , Glioblastoma/patología , Glioblastoma/metabolismo , Pronóstico , ARN Interferente Pequeño/genética , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismoRESUMEN
Objective: To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis. Methods: In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed. Results: The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 2
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Adenoma , Hiperaldosteronismo , Hipertensión , Masculino , Humanos , Femenino , Persona de Mediana Edad , Renina , Aldosterona , Hiperaldosteronismo/diagnóstico , Estudios RetrospectivosRESUMEN
Acute lymphoblastic leukemia (ALL) is a malignant disease of the hematopoietic system. At present, the mechanism and pathogenesis of ALL have not been fully clarified. This study aimed to illustrate the roles of Cdc10 protein-dependent transcript 1 (CDT1) in ALL. Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) was performed to examine serum levels of CDT1 in childhood ALL patients and healthy volunteers. The interaction between CDT1 expression and prognosis of childhood ALL was analyzed. Meanwhile, expressions of CDT1 in ALL cell lines were determined. Furthermore, CDT1 knockdown model was constructed in ALL cells, and Cell Counting Kit-8 (CCK-8), and Transwell assays were conducted to analyze the effect of CDT1 on the biological functions of ALL cells. Potential mechanism was further explored through detecting the expressions of Epithelial-to-mesenchymal transition (EMT)-related genes. RT-qPCR results indicated that serum level of CDT1 in childhood ALL patients was remarkably higher than that of healthy volunteers. Childhood ALL patients with high expression of CDT1 had lower overall survival rate compared with those expressing low expression of CDT1. CDT1 knockdown remarkably decreased the proliferation and metastasis abilities of pediatric ALL cells. Results of western blot showed that CDT1 might contribute to the malignant progression of childhood ALL via activating EMT. The findings showed that elevated CDT1 facilitated ALL metastasis by promoting EMT, suggesting that CDT1 played a pivotal role in ALL metastasis and may serve as a novel prognostic biomarker and therapeutic target.
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Transición Epitelial-Mesenquimal , Leucemia-Linfoma Linfoblástico de Células Precursoras , Proteínas de Ciclo Celular/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMEN
Objective: To construct and evaluate a diagnosis pathway (Xiangya pathway) for Corona Virus Disease 2019 (COVID-19). Methods: Consecutive subjects aged ≥12 years old who were screened for COVID-19 were included in Xiangya Hospital of Central South University from January 23 to February 3, 2020, and the subjects were further divided into the inception cohort and the validation cohort. The gender, age, onset time of disease of the subjects were recorded. The information of epidemiological history, fever, and the declined blood lymphocytes were collected as clinical indicators, CT scan was used to evaluate the possibility of COVID-19 and range of lung involvement. According to the current Chinese national standards, throat swabs of suspected cases were collected and the nucleic acid of COVID-19 was detected by reverse transcription-polymerase chain reaction (RT-PCR). The Xiangya pathway was constructed with multi-indexes, compared with clinical indicators, CT results and Chinese national standards, their effectiveness of detecting confirmed cases were verified in the inception and validation cohort. Results: A total of 382 consecutive adults who was screened for COVID-19 were included, and 261 cases were in the inception cohort and 121 cases were in the validation cohort. Among the 382 cases, 192 were males (50.3%) and 190 were females (49.7%), with a median age of 35 years (range: 15-92 years). There were 183 cases (47.9%) with epidemiological history, 275 cases (72.0%) with fever, 212 cases (55.5%) with decreased peripheral blood lymphocytes, 114 cases (29.8%) with positive CT findings, 43 cases (11.3%) with positive CT-COVID-19, and 30 cases (7.9%) with positive virus nucleic acid by throat swab. Compared with clinical indicators, the sensitivity and specificity of CT were 0.950 and 0.704, respectively. The accuracy of CT to make a definite diagnosis was higher than that of epidemiological history, fever, and declined blood lymphocyte count (0.809 vs 0.660, 0.532, 0.596, P=0.001, 0.002, 0.003, respectively). The sensitivity of this pathway and the pathway recommended by the Health Commission of China were both high (all were 1.000), while the specificity and accuracy of the Xiangya pathway were higher than the one recommended by the Health Commission (0.872 vs 0.765, 0.778 vs 0.592, both P<0.001). The CT-COVID-19 reduced the missed diagnosis rate caused by false negative of nucleic acid test (31 vs 64), with difference rate of 51.6%, and the positive rate of nucleic acid test was 64.5% (20/31). In validation cohort, the specificity and accuracy of the Xiangya pathway was 0.967, the positive rate of nucleic acid test was 76.9%(10/13). Conclusions: The Xiangya pathway can predict the nucleic acid test results of COVID-19, and can be applied as a reliable strategy to screen patients with suspected COVID-19 among people aged ≥12 years in areas other than Hubei during the epidemic period of COVID-19. The cohort size needs to be increased for further validation.
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Betacoronavirus , Infecciones por Coronavirus , Pandemias , Neumonía Viral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , COVID-19 , Prueba de COVID-19 , China , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neumonía Viral/diagnóstico , SARS-CoV-2 , Adulto JovenRESUMEN
Objective: To study the segment of liver according to the large amount of three-dimensional(3D) reconstructive images of normal human livers and the vascular system, and to recognize the basic functional liver unit based on the anatomic features of the intrahepatic portal veins. Methods: The enhanced CT primitive DICOM files of 1 260 normal human livers from different age groups who treated from October 2013 to February 2017 provided by 16 hospitals were analyzed using the computer-aided surgery system.The 3D liver and liver vascular system were reconstructed, and the digital liver 3D model was established.The vascular morphology, anatomical features, and anatomical distributions of intrahepatic portal veins were statistically analyzed. Results: The digital liver model obtained from the 3D reconstruction of CAS displayed clear intrahepatic portal vein vessels of level four.Perform a digital liver segments study based on the analysis of level four vascular distribution areas.As the less anatomical variation of left hepatic portal vein, the liver was classified into four types of liver segmentation mainly based on right hepatic portal vein.Type A was similar to Couinaud or Cho's segmentation, containing 8 segments(537 cases, 42.62%). Type B contained 9 segments as there are three ramifications of right-anterior portal vein(464 cases, 36.82%). The main difference for Type C was the variation of right-posterior portal vein which was sector shape(102 cases, 8.10%). Type D contained the cases with special portal vein variations, which needs three-dimensional simulation to design individualized liver resection plan(157 cases, 12.46%). These results showed that there was no significant difference in liver segmental typing between genders(χ(2)=2.179, P=0.536) and did not reveal any significant difference in liver segmental typing among the different age groups(χ(2)=0.357, P=0.949). Conclusions: The 3D digital liver model can demonstrate the true 3D anatomical structures, and its spatial vascular variations.The observation of anatomic features, distribution areas of intrahepatic portal veins and individualized liver segmentation achieved via digital medical 3D visualization technology is of great value for understand the complexity of liver anatomy and to guide the precise hepatectomy.
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Hepatectomía , Venas Hepáticas , Vena Porta , Cirugía Asistida por Computador , Femenino , Venas Hepáticas/cirugía , Humanos , Imagenología Tridimensional , Hígado/cirugía , Masculino , Vena Porta/cirugíaRESUMEN
Objective: To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province. Methods: This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized. Results: Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion: Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.
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Hemoglobinuria Paroxística , Humanos , Hemoglobinuria Paroxística/epidemiología , Hemoglobinuria Paroxística/diagnóstico , Hemoglobinuria Paroxística/terapia , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Estudios Retrospectivos , Adulto Joven , Anciano , China/epidemiología , Anciano de 80 o más AñosRESUMEN
Magnetic carbon nanotube (mCNT) was formed via direct mixing of carbon nanotube (CNT) with magnetic nanoparticle (MNP) in dye solution. When the mass ratio of MNP to CNT was 4:1, all CNT were magnetically collected. The adsorption performance of mCNT was evaluated using methyl blue (MB) as a model adsorbate. Equilibrium of MB adsorption was attained in 60 min, and maximum adsorption occurred at pH 3-6. MB adsorption was independent of ionic strength and followed pseudo-second-order kinetics. According to the Langmuir isotherm, adsorption capacity of mCNT for MB was 115.34 mg g(-1). Thermodynamic analysis suggested MB adsorption onto mCNT was a spontaneous process. Reusability study results showed that 97.06, 96.26, 94.33, 92.91 and 90.14% of MB were removed in five consecutive cycles. The study suggests that the mCNT has a great potential application in dye removal from industrial wastewater.
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Bencenosulfonatos/aislamiento & purificación , Nanopartículas de Magnetita/química , Nanotubos de Carbono/química , Contaminantes Químicos del Agua/aislamiento & purificación , Purificación del Agua/métodos , Adsorción , Bencenosulfonatos/química , Colorantes/química , Colorantes/aislamiento & purificación , Equipo Reutilizado , Concentración de Iones de Hidrógeno , Cinética , Concentración Osmolar , Termodinámica , Factores de Tiempo , Contaminantes Químicos del Agua/químicaRESUMEN
Objective: To explore the incidence, clinical and microbiological characteristics and risk factors of infection in patients with acute lymphoblastic (ALL) , non-Hodgkin lymphoma (NHL) , and multiple myeloma (MM) within 28 days after CAR-T cell infusion. It provides data support for early identification of infection and the rational use of antibacterial drugs in these patients. Methods: We retrospectively analyzed the baseline data of 170 patients with ALL, NHL and MM who received chimeric antigen receptor-modified T (CAR-T) -cell treatment in the Department of Hematology of Wuhan Union Hospital from January 2016 to December 2020, and the clinical characteristics of infection within 28 days after infusion, including 72 patients with ALL, 56 patients with NHL, and 42 patients with MM; we used Poisson regression and Cox proportional hazard regression models to assess high-risk factors for infection before and after infusion, respectively. Results: Among 170 patients, 119 infections occurred in 99 patients within 28 days, with a cumulative infection rate of 58.2%. Seventy-eight patients had 98 bacterial infections and the cumulative incidence of bacterial infection was 45.9%. The infection density was 2.01, and the median time for the first infection was about 12 days after infusion. The adjusted baseline characteristic model showed that ALL patients, previous 30 days of infection history, refractory disease, absolute neutrophil count (ANC) <0.5×10(9)/L before infusion and ≥4 prior antitumor treatment regimens had a higher infection density within 28 days; grade 3 or 4 CRS was the only high-risk factor related to infection after infusion in the multivariate analysis. Conclusion: Infection is a common complication of CAR-T cell therapy in patients with hematologic malignancy. Bacterial infections occur in most patients regardless of the type of disease. ALL patients, previous 30 days of infection history, refractory disease, ANC<0.5×10(9)/L before infusion and grade 3 or 4 CRS are risk factors for infection. Chinese Clinical Trial Register:: ChiCTR-OIC-17011180, ChiCTR1800018143.
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Neoplasias Hematológicas , Inmunoterapia Adoptiva , Infecciones/etiología , Antígenos CD19 , Tratamiento Basado en Trasplante de Células y Tejidos , Neoplasias Hematológicas/complicaciones , Neoplasias Hematológicas/terapia , Humanos , Receptores de Antígenos de Linfocitos T , Receptores Quiméricos de Antígenos , Estudios RetrospectivosRESUMEN
A novel genetic selection was used to identify genes regulating traffic in the yeast endosomal system. We took advantage of a temperature-sensitive mutant in PMA1, encoding the plasma membrane ATPase, in which newly synthesized Pma1 is mislocalized to the vacuole via the endosome. Diversion of mutant Pma1 from vacuolar delivery and rerouting to the plasma membrane is a major mechanism of suppression of pma1(ts). 16 independent suppressor of pma1 (sop) mutants were isolated. Identification of the corresponding genes reveals eight that are identical with VPS genes required for delivery of newly synthesized vacuolar proteins. A second group of SOP genes participates in vacuolar delivery of mutant Pma1 but is not essential for delivery of the vacuolar protease carboxypeptidase Y. Because the biosynthetic pathway to the vacuole intersects with the endocytic pathway, internalization of a bulk membrane endocytic marker FM 4-64 was assayed in the sop mutants. By this means, defective endosome-to-vacuole trafficking was revealed in a subset of sop mutants. Another subset of sop mutants displays perturbed trafficking between endosome and Golgi: impaired pro-alpha factor processing in these strains was found to be due to defective recycling of the trans-Golgi protease Kex2. One of these strains defective in Kex2 trafficking carries a mutation in SOP2, encoding a homologue of mammalian synaptojanin (implicated in synaptic vesicle endocytosis and recycling). Thus, cell surface delivery of mutant Pma1 can occur as a consequence of disturbances at several different sites in the endosomal system.
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Endosomas/enzimología , Endosomas/genética , Mutagénesis , Proproteína Convertasas , ATPasas de Translocación de Protón/genética , Proteínas de Saccharomyces cerevisiae , Proteínas de Transporte Vesicular , Transporte Biológico/genética , Biomarcadores , Proteínas Portadoras/genética , Membrana Celular/enzimología , Membrana Celular/genética , Membrana Celular/metabolismo , Endosomas/metabolismo , Proteínas Fúngicas/genética , Membranas Intracelulares/enzimología , Factor de Apareamiento , Proteínas del Tejido Nervioso/genética , Péptidos/genética , Monoéster Fosfórico Hidrolasas/genética , Procesamiento Proteico-Postraduccional , Receptores de Superficie Celular/genética , Saccharomyces cerevisiae , Subtilisinas/metabolismo , Vacuolas/química , Vacuolas/enzimología , Vacuolas/genéticaRESUMEN
OBJECTIVE: MiR-1231 has been reported to be down-regulated in glioma tissues and to act as a negative regulator in glioma progression. However, the clinical significance of miR-1231 remains unclear. In this study, we aimed to further demonstrate the expression pattern and prognostic value of miR-1231 in glioma patients. PATIENTS AND METHODS: We determined the expression level of miR-1231 in 154 cases of paired glioma and adjacent non-tumor tissues by quantitative Real Time-PCR (qRT-PCR). The association between miR-1231 expression levels and clinicopathological factors was examined by the χ2 test. The Kaplan-Meier survival analysis was performed to analyze the association of miR-1231 expression with overall survival (OS) and progression-free survival (PFS) of patients. The significance of survival variables was analyzed using the Cox multivariate proportional hazards model. RESULTS: We found that the expression level of miR-1231 in human glioma tissues was significantly lower than that in the adjacent nontumorous tissues (p<0.01). The expression levels of miR-1231 in glioma tissues with high grades were significantly lower than those with low grades. Decreased miR-1231 expression was significantly associated with advanced WHO grade (p=0.001) and KPS score (p=0.023). The Kaplan-Meier analysis indicated that low miR-1231 expression had a significant impact on OS (p=0.0103) and PFS (p=0.0019). Cox proportional hazards risk analysis demonstrated that miR-1231 was an independent prognostic factor for glioma. CONCLUSIONS: Our study, for the first time, provides evidence that evaluating miR-1231 in glioma may have prognostic and predictive value in the clinical management of glioma.
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Neoplasias Encefálicas/genética , Glioma/genética , MicroARNs/genética , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/terapia , Regulación hacia Abajo , Femenino , Regulación Neoplásica de la Expresión Génica , Glioma/mortalidad , Glioma/patología , Glioma/terapia , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Supervivencia sin Progresión , Medición de Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
The plasma membrane ATPase, encoded by PMA1, is delivered to the cell surface via the secretory pathway. Previously, we characterized a temperature-sensitive pma1 mutant in which newly synthesized Pma1-7 is not delivered to the plasma membrane but is mislocalized instead to the vacuole at 37 degrees C. Several vps mutants, which are defective in vacuolar protein sorting, suppress targeting-defective pma1 by allowing mutant Pma1 to move once again to the plasma membrane. In this study, we have analyzed trafficking in the endosomal system by monitoring the movement of Pma1-7 in vps36, vps1, and vps8 mutants. Upon induction of expression, mutant Pma1 accumulates in the prevacuolar compartment in vps36 cells. After chase, a fraction of newly synthesized Pma1-7 is delivered to the plasma membrane. In both vps1 and vps8 cells, newly synthesized mutant Pma1 appears in small punctate structures before arrival at the cell surface. Nevertheless, biosynthetic membrane traffic appears to follow different routes in vps8 and vps1: the vacuolar protein-sorting receptor Vps10p is stable in vps8 but not in vps1. Furthermore, a defect in endocytic delivery to the vacuole was revealed in vps8 (and vps36) but not vps1 by endocytosis of the bulk membrane marker FM 4-64. Moreover, in vps8 cells, there is defective down-regulation from the cell surface of the mating receptor Ste3, consistent with persistent receptor recycling from an endosomal compartment to the plasma membrane. These data support a model in which mutant Pma1 is diverted from the Golgi to the surface in vps1 cells. We hypothesize that in vps8 and vps36, in contrast to vps1, mutant Pma1 moves to the surface via endosomal intermediates, implicating an endosome-to-surface traffic pathway.
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Membrana Celular/metabolismo , Endosomas/enzimología , Endosomas/metabolismo , Mutación/genética , ATPasas de Translocación de Protón/metabolismo , Receptores Acoplados a Proteínas G , Receptores de Feromonas , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/citología , Proteínas de Transporte Vesicular , Transporte Biológico , Proteínas Portadoras/genética , Proteínas Portadoras/fisiología , Membrana Celular/enzimología , Endocitosis , Técnica del Anticuerpo Fluorescente Indirecta , Proteínas Fúngicas/biosíntesis , Proteínas Fúngicas/metabolismo , Genes Fúngicos/genética , Genes Fúngicos/fisiología , Modelos Biológicos , ATPasas de Translocación de Protón/biosíntesis , ATPasas de Translocación de Protón/genética , Compuestos de Piridinio , Compuestos de Amonio Cuaternario , Receptores de Superficie Celular/biosíntesis , Receptores de Superficie Celular/metabolismo , Receptores del Factor de Conjugación , Proteínas Recombinantes de Fusión/biosíntesis , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Factores de Tiempo , Vacuolas/enzimología , Vacuolas/metabolismoRESUMEN
BACKGROUND: Our previous work has shown that preconditioning can promote the recovery of cardiac function in patients having an open heart procedure. Because preconditioning is regarded as the most powerful form of endogenous myocardial protection, we tested the hypothesis that preconditioning protects against myocardial ischemia-reperfusion injury in patients undergoing prolonged cold crystalloid cardioplegic arrest. METHODS: Thirty patients who had rheumatic heart disease and required both aortic and mitral valve replacement were studied. Patients were randomly divided into two equal groups. Preconditioning was accomplished using two cycles of 2-minute occlusion of the vena cava and aorta followed by 3 minutes of reperfusion under cardiopulmonary bypass. All hearts were arrested with 4 degrees C St. Thomas' Hospital cardioplegic solution. Myocardial protective effects were assessed by changes in myocardial levels of adenosine triphosphate, electrocardiographic activity, leakage of myocardial enzymes, and myocardial contractility. RESULTS: The adenosine triphosphate content in ischemic myocardium was higher in the preconditioning group than in the control group (p < 0.05 90 minutes after ischemia), and there was a significant reduction in release of the myocardial-specific isoenzyme of creatine kinase in the preconditioning group. Preconditioning improved the recovery of myocardial contractility (first derivative of left ventricular developed pressure, 1,490 +/- 102 mm Hg/s versus 1,250 +/- 97 mm Hg/s 30 minutes after reperfusion; p < 0.05), and there was also a protective effect on electrocardiographic activity. CONCLUSIONS: Our results suggest that ischemic preconditioning protects the myocardium in humans from the severe ischemia-reperfusion injury produced after prolonged arrest with cold crystalloid cardioplegia.
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Procedimientos Quirúrgicos Cardíacos , Válvulas Cardíacas/cirugía , Precondicionamiento Isquémico Miocárdico , Adenosina Trifosfato/análisis , Adulto , Creatina Quinasa/metabolismo , Electrocardiografía , Femenino , Paro Cardíaco Inducido , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Isoenzimas , Masculino , Contracción Miocárdica , Reperfusión Miocárdica , Miocardio/metabolismo , Presión VentricularRESUMEN
This study investigates transient electroosmotic flow in a rectangular curved microtube in which the fluid is driven by the application of an external DC or AC electric field. The resultant flow-field evolutions within the microtube are simulated using the backwards-Euler time-stepping numerical method to clarify the relationship between the changes in the axial-flow velocity and the intensity of the applied electric field. When the electric field is initially applied or varies, the fluid within the double layer responds virtually immediately, and the axial velocity within the double layer tends to follow the varying intensity of the applied electric field. The greatest net charge density exists at the corners of the microtube as a result of the overlapping electrical double layers of the two walls. It results in local maximum or minimum axial velocities in the corners during increasing or decreasing applied electric field intensity in either the positive or negative direction. As the fluid within the double layer starts to move, the bulk fluid is gradually dragged into motion through the diffusion of momentum from the double layer. A finite time is required for the full momentum of the double layer to diffuse to the bulk fluid; hence, a certain phase shift between the applied electric field and the flow response is inevitable. The patterns of the axial velocity contours during the transient evolution are investigated in this study. It is found that these patterns are determined by the efficiency of momentum diffusion from the double layer to the central region of the microtube.
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BACKGROUND: The purpose of this study was to evaluate the effects of three different methods of cardioprotection in patients undergoing valve replacement. METHODS: Ninety patients undergoing elective valve replacement were randomly divided into three groups. In group 1 (n=30), the patients received intermittent cold blood cardioplegia. In group 2 (n=30) they received terminal warm cardioplegia and controlled reperfusion, and in group 3 (n=30), the patients received two cycles of ischemia (2 minutes) and reperfusion (3 minutes) before heart arrest induced by cold blood cardioplegia. The parameters of cardiac function, creatine kinase MB, and clinical outcomes were recorded to assess the effects of experiment. RESULTS: The major preoperative and intraoperative variables are comparable within the three groups. The number of patients requiring the support of inotropic agents was 70% (21/30), 33% (11/30) and 40% (12/30) in group 1, 2 and 3, respectively (p<0.05). The doses of inotropic agent in groups 2 and 3, were significantly lower than in group 1 (1.5+/-0.3 and 1.8+/-0.4 versus 4.5+/-0.8 microg x kg x min(-1), p<0.01) during the first 24 hours after operation. Two deaths (30 day-hospital mortality) occurred, one in group 1 and one in group 2. The cardiac index at 2 hours after bypass discontinuing were 2.2+/-0.04, 3.0+/-0.1 and 2.8+/-0.05 L/m(2) in group 1, 2 and 3, respectively (p<0.01). The left ventricular stroke work index were 24.8+/-1.3, 34.5+/-1.6 and 31.6+/-1.2 g/m x m(2) in group 1, 2, 3, respectively (p<0.01). The release of CK-MB in group 2 and 3 were lower than in group 1 (68+/-7, 81+/-9 versus 116+/-10 IU/L, p<0.01). CONCLUSIONS: Terminal warm cardioplegia with controlled aortic root reperfusion and ischemic preconditioning equally improve cardiac function and reduce the requirement of inotropic agents in patients undergoing valve replacement.
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Paro Cardíaco Inducido , Implantación de Prótesis de Válvulas Cardíacas , Precondicionamiento Isquémico Miocárdico , Adulto , Gasto Cardíaco , Femenino , Paro Cardíaco Inducido/métodos , Implantación de Prótesis de Válvulas Cardíacas/mortalidad , Humanos , Masculino , Complicaciones Posoperatorias/epidemiologíaRESUMEN
Using Electron Spectroscopic Imaging (ESI), we visualized the in situ binding of nucleic acids to nuclear matrix and 3H-thymidine incorporation which indicates that a small partial DNA bound to nuclear matrix tightly. Furthermore we found that chromosomal telomere DNA could bind to nuclear matrix specifically by the dot and Southern hybridization. The result of the Southwestern blot suggests that telomere DNA has high affinity to lamin B, vimentin and some nuclear matrix proteins. Therefore, the nuclear matrix and lamina of HeLa cell are possibly associated with spatial organization and action of chromosome.
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ADN/metabolismo , Telómero/metabolismo , Células HeLa , Humanos , Lamina Tipo B , Laminas , Matriz Nuclear/metabolismo , Proteínas Nucleares/metabolismo , Vimentina/metabolismoRESUMEN
Manganese is a common environmental and occupational pollutant. Excessive intake of manganese can cause toxicity known as manganism. Recently it has been demonstrated that unusual expression of cell cycle proteins and aberrant cell cycle progression in the central nervous system are involved in the pathogenesis of neurodegenerative diseases. The present studies were initiated to investigate whether p21 are induced after manganese exposure and its potential effects in vitro, with particular attention being given to understand the underlying regulatory mechanism of p21 induction by manganese in this process. We found that manganese induced DAergic cells injury and upregulation of p21 levels in nigrostriatal regions. Treatment of the PC12 cells with manganese resulted in a time- and concentration-dependent loss of cell viability. Analysis of cell cycle profile indicated that manganese blocked cell cycle progression by arresting the cell cycle at G2/M phase. Moreover, manganese treatment resulted in an increase in the mRNA and protein levels of p21, but did not have the same effect on other related factors. Silencing p21 by RNA interference showed a marked reversal of both G2/M arrest and the decrease in cell viability induced by manganese. Manganese did not stabilize the p21 protein and mRNA, and caused a marked increase in p21 mRNA levels together with an increase in its promoter activity, indicating a transcriptional mechanism. Overall, the in vivo and in vitro data suggest that exposure to manganese can increase p21 levels. An altered cell cycle status of PC12 cells can be induced by manganese through p21 up-regulation, and the induction of p21 occurs at the transcriptional level via promoter activation and mRNA induction.
Asunto(s)
Cloruros/farmacología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidores Enzimáticos/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Compuestos de Manganeso/farmacología , Células PC12/efectos de los fármacos , Factores de Edad , Análisis de Varianza , Animales , Ciclo Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Relación Dosis-Respuesta a Droga , Masculino , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Transfección , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Nuclei assembled in Xenopus egg extracts from exogenous DNA or chromatin are morphologically similar to normal eukaryotic nuclei except that they do not contain nucleolus-like structure. Previous work show that prenucleolar bodies could be found in these nuclei, but they are unable to fuse with each other, probably due to the absence of a functional nucleolus organizer. It is interesting to know if exogenous functional nuclei could act as functional nucleolus organizer to induce the formation of mature nucleoli. To test this possibility, nucleoli and demembranated macronuclei which contain perinuclear distributed nucleoli were isolated and purified from Tetrahymena shanghaiensis and were introduced into Xenopus cell-free system. By EM observation, we showed that these nucleoli, both individual isolated and perinuclear distributed, could not keep their original morphological characteristic, but undergo a series of structural changes resembling nuclear assembly induced by exogenous chromatin. No nucleolus-like structure was found in these nuclear like structure. These results indicate that functional nucleolus organizers could neither keep their original activity of RNA transcription nor induce the formation of new nucleoli in Xenopus egg extracts.