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Substantial morbidity and mortality are associated with postcardiac arrest brain injury (PCABI). MicroRNAs(miRNAs) are essential regulators of neuronal metabolism processes and have been shown to contribute to alleviated neurological injury after cardiac arrest. In this study, we identified miRNAs related to the prognosis of patients with neurological dysfunction after cardiopulmonary resuscitation based on data obtained from the Gene Expression Omnibus (GEO) database. Then, we explored the effects of miR-483-5p on mitochondrial biogenesis, mitochondrial-dependent apoptosis, and oxidative stress levels after ischemiaâreperfusion injury in vitro and in vivo. MiR-483-5p was downregulated in PC12 cells and hippocampal samples compared with that in normal group cells and hippocampi. Overexpression of miR-483-5p increased the viability of PC12 cells after ischemiaâreperfusion injury and reduced the proportion of dead cells. A western blot analysis showed that miR-483-5p increased the protein expression of PCG-1, NRF1, and TFAM and reduced the protein expression of Bax and cleaved caspase 3, inhibiting the release of cytochrome c from mitochondria and alleviating oxidative stress injury by inhibiting the production of ROS and reducing MDA activity. We confirmed that miR-483-5p targeted TNFSF8 to regulate the AMPK/JNK pathway, thereby playing a neuroprotective role after cardiopulmonary resuscitation. Hence, this study provides further insights into strategies for inhibiting neurological impairment after cardiopulmonary resuscitation and suggests a potential therapeutic target for PCABI.
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Paro Cardíaco , MicroARNs , Fármacos Neuroprotectores , Daño por Reperfusión , Ratas , Animales , Humanos , Sistema de Señalización de MAP Quinasas , Fármacos Neuroprotectores/farmacología , Proteínas Quinasas Activadas por AMP/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Apoptosis/genética , Daño por Reperfusión/metabolismo , Mitocondrias/metabolismo , Paro Cardíaco/complicaciones , Paro Cardíaco/genética , Paro Cardíaco/metabolismoRESUMEN
Urethral amyloidosis (UA) is a very rare condition. We here report the case of a 63-year-old male patient who was admitted to our outpatient department due to aggravating dysuria, frequent urination, pain during intercourse, and a gradually enlarging mass at the ostium of his urethra, which he first notice one year earlier. Pathological tissue biopsy of urethral ostium mass confirmed UA. Intermittent urethra infusion of dimethyl sulfoxide was performed and the treatment effect is satisfactory.
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Amiloidosis , Enfermedades Uretrales , Amiloidosis/complicaciones , Amiloidosis/tratamiento farmacológico , Amiloidosis/patología , Biopsia , Dimetilsulfóxido , Humanos , Masculino , Uretra/patologíaAsunto(s)
Antagonistas de Receptores Adrenérgicos alfa 1 , Hiperplasia Prostática , Tamsulosina , Humanos , Tamsulosina/uso terapéutico , Tamsulosina/administración & dosificación , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/cirugía , Hiperplasia Prostática/complicaciones , Masculino , Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Antagonistas de Receptores Adrenérgicos alfa 1/uso terapéutico , Insuficiencia del TratamientoRESUMEN
OBJECTIVE: Recent studies have shown the existence of autophagy in cerebral ischemia; however, there has been no research on the role of autophagy in cerebral injury after cardiopulmonary resuscitation (CPR). This study was conducted to determine the role of autophagy in an animal model of ventricular fibrillation (VF)/CPR. METHODS: Experiment 1: A total of 48 adult Wistar rats were untreated for 7 minutes after induction of VF using an external transthoracic alternating current, and subsequent CPR was performed to observe the existence of autophagy after the return of spontaneous circulation (ROSC). Experiment 2: A total of 72 rats were pretreated with intracerebroventricular injection of physiologic saline (control group), the autophagy inducer (rapamycin group), or the autophagy inhibitor 3-methyladenine (3-methyladenine group) before ROSC to evaluate the contribution of autophagy to neuronal injury after ROSC. RESULTS: The activation of autophagy was attenuated 2 to 4 hours after ROSC, which was related to the activity decrease of 5'-adenosine monophosphate-activated protein kinase after ROSC. Rapamycin treatment significantly increased the expressions of LC3-II and Beclin-1 after ROSC, attenuated the activation of caspase-3, promoted neuronal survival and decreased neuronal apoptosis, and improved the neurologic deficit score after CPR. CONCLUSIONS: The activation of autophagy after ROSC offered a remarkable tolerance to VF/CPR ischemic insult and improved the neurologic outcomes.
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Autofagia/fisiología , Isquemia Encefálica/patología , Reanimación Cardiopulmonar/métodos , Paro Cardíaco/terapia , Animales , Isquemia Encefálica/etiología , Isquemia Encefálica/metabolismo , Modelos Animales de Enfermedad , Paro Cardíaco/complicaciones , Paro Cardíaco/metabolismo , Paro Cardíaco/patología , Masculino , Ratas , Ratas WistarRESUMEN
PURPOSE: To demonstrate the effect of total reconstruction technique on postoperative urinary continence after laparoscopic radical prostatectomy (LRP). MATERIAL AND METHODS: LRP was performed using a standard urethrovesical anastomosis in 79 consecutive patients (Group-A) from June 2011 to October 2012, and a total reconstruction procedure in 82 consecutive patients (Group-B) from June 2012 to June 2013. The primary outcome measurement was urinary continence assessed at 1, 2, 4, 12, 24 and 52 weeks after catheter removal. Other data recorded were patient age, body mass index, International Prostate Symptoms Score, prostate volume, preoperative PSA, Gleason score, neurovascular bundle preservation, operation time, estimated blood loss, complications and pathology results. RESULTS: In Group-A, the continence rates at 1, 2, 4, 12, 24 and 52 weeks were 7.59%, 20.25%, 37.97%, 58.22%, 81.01% and 89.87% respectively. In Group-B, the continence rates were 13.41%, 32.92%, 65.85%, 81.71%, 90.24% and 95.12% respectively. Group-B had significantly higher continence rates at 4 and 12 weeks after surgery (P<0.001 and P=0.001). There were no significant differences between the groups with respect to patient's age, body mass index, prostate-specific antigen level, prostate volume, IPSS, estimated blood loss, number of nerve-sparing procedures and postoperative complications. CONCLUSIONS: Total reconstruction technique in the procedure of urethrovesical anastomosis during LRP improved early recovery of continence.
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Laparoscopía/métodos , Procedimientos de Cirugía Plástica/métodos , Prostatectomía/métodos , Uretra/cirugía , Vejiga Urinaria/cirugía , Anciano , Anastomosis Quirúrgica , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Tempo Operativo , Complicaciones Posoperatorias , Antígeno Prostático Específico/sangre , Prostatectomía/efectos adversos , Prostatectomía/rehabilitación , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/cirugía , Recuperación de la Función , Reproducibilidad de los Resultados , Estudios Retrospectivos , Resultado del Tratamiento , Incontinencia Urinaria/etiología , Incontinencia Urinaria/prevención & controlRESUMEN
To study the changes of cerebral glucose metabolism (CGM) during the phase of return of spontaneous circulation (ROSC) after cardiac arrest (CA), we used 18-fluorodeoxyglucose-positron emission tomography/computed tomography ((18)FDG-PET/CT) to measure the CGM changes in six beagle canine models. After the baseline (18)FDG-PET/CT was recorded, ventricular fibrillation (VF) was induced for 6 min, followed by close-chest cardiopulmonary resuscitation (CPR) in conjunction with intravenous (IV) administration of epinephrine and external defibrillator shocks until ROSC was achieved, within 30 min. The (18)FDG was recorded prior to intravenous administration at 0 h (baseline), and at 4, 24, and 48 h after CA with ROSC. We evaluated the expression of two key control factors in canine CGM, hexokinase I (HXK I) and HXK II, by immunohistochemistry at the four above mentioned time points. Electrically induced VF of 6 min duration was successfully induced in the dogs. Resuscitation was then performed to maintain blood pressure stability. Serial (18)FDG-PET/CT scans found that the CGM decreased at 4 h after ROSC and remained lower than the baseline even at 48 h. The expression of HXK I and II levels were consistent with the changes in CGM. These data from our present work showed that (18)FDG-PET/CT imaging can be used to detect decreased CGM during CA and was consistent with the results of CMRgl. Furthermore, there were also concomitant changes in the expression of HXK I and HXK II. The decrease in CGM may be an early sign of hyperacute global cerebral ischemia.
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Encéfalo/metabolismo , Fluorodesoxiglucosa F18 , Glucosa/metabolismo , Paro Cardíaco/metabolismo , Tomografía de Emisión de Positrones , Tomografía Computarizada por Rayos X , Animales , Encéfalo/diagnóstico por imagen , Circulación Cerebrovascular/fisiología , Perros , Paro Cardíaco/complicaciones , MasculinoRESUMEN
A rapid and sensitive liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method to determine clonidine in human plasma was developed and fully validated. Sample preparation was involved an one-step extraction with diethyl ether. Donepezil was employed as the internal standard (IS). Chromatographic separation was performed on a Hypersil BDS C18 column (i.d. 2.1 × 50 mm, particle size 3µm) with a mobile phase of methanol-water (containing 0.1% formic acid; 60:40, v/v) at a flow rate of 200 µL/min. The peaks were detected by mass spectrometry using the electrospray ion source in selected reaction monitoring mode. The extraction recovery was 72.53-85.25%. The method was found to be linear in a concentration range of 0.02-6.00 ng/mL and the lower limit of quantification was 0.02 ng/mL. The within- and between-batch precisions at three concentrations were 4.33-16.47 and 7.24-17.24% with accuracies of -2.47-10.91 and 1.86-10.19%, respectively. This validated method was successfully used for a bioequivalence study of two clonidine transdermal patches on healthy volunteers. The results suggested that the test formulation of clonidine patch met the regulatory criterion for bioequivalence to the reference formulation, but a larger sample size should be needed for the estimation of bioequivalence.
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Cromatografía Líquida de Alta Presión/métodos , Clonidina/sangre , Clonidina/farmacocinética , Adulto , Área Bajo la Curva , Calibración , Clonidina/administración & dosificación , Voluntarios Sanos , Humanos , Masculino , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Equivalencia Terapéutica , Parche TransdérmicoRESUMEN
OBJECTIVE: To explore the safety and efficacy of "sandwich" urethra reconstruction in laparoscopic radical prostatectomy (LRP) for the early recovery of continence. METHODS: LRP was performed using a urethra surrounding tissue reconstruction in 37 consecutive patients, and without reconstruction procedure in 34 consecutive patients at the same period from March 2012 to January 2013. The baseline data, preoperative data: The patient age, body mass index (BMI, kg/m2), International prostate symptoms score (IPSS), prostate volume, preoperative PSA, Gleason score were assessed retrospectively; Operative data: The neurovascular bundle preservation, operation time, blood loss were assessed; and the primary outcome measure was urinary continence assessed at the end of 1, 2, 4, 12 and 24 weeks after the catheter was removed. Other data recorded were duration of indwelling catheter, positive margin rate and complications. RESULTS: There were no significant differences between the two groups with respect to baseline,preoperative and operative data except of the operative time (P=0.003). Between the two groups, the continence of the reconstruction group was higher than that of the control group at the end of 4 and 12 weeks (P=0.007, P=0.020, respectively). CONCLUSION: Urethra surrounding tissue reconstruction in LRP is safe and feasible, and it could improve early recovery of continence.
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Procedimientos de Cirugía Plástica , Neoplasias de la Próstata/cirugía , Uretra/cirugía , Incontinencia Urinaria/prevención & control , Humanos , Laparoscopía , Masculino , Tempo Operativo , ProstatectomíaRESUMEN
OBJECTIVES: The aim of this study was to investigate whether early enhanced external counter pulsation therapy after cardiopulmonary resuscitation improved neurological outcome in a mongrel dog cardiac arrest model. DESIGN: Randomized, animal study. SETTING: Assisted circulation laboratory. SUBJECTS: Twenty-four healthy male adult dogs (12-14 kg). INTERVENTIONS: After minutes of untreated ventricular fibrillation followed by 2 minutes of cardiopulmonary resuscitation, the dogs were randomized to receive 4 hours of enhanced external counter pulsation therapy, to receive 4 hours of hypertension with over 140 mm Hg or to be a control. MEASUREMENTS: Blood pressure and left ventricular ejection fraction were recorded. Cerebral flow was assessed using magnetic resonance imaging. Arterial blood gases and endothelium-derived vasoactive substances were assessed before cardiac arrest and 4 hours after the return of spontaneous circulation. Neurological outcome was assessed by the neurologic deficit score and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. RESULTS: Enhanced external counter pulsation significantly improved the left ventricular ejection fraction and increased common carotid artery blood flow and shear stress. Enhanced external counter pulsation increased both relative cerebral blood volume (RCBV, p = 0.043) and relative cerebral blood flow (RCBF, p = 0.012) in animals 4 hours after return of spontaneous circulation. Enhanced external counter pulsation therapy promoted the production of nitric oxide and tissue plasminogen activator and decreased the release of endothelin-1 (p = 0.013) after return of spontaneous circulation. Treatment with norepinephrine in the high mean artery pressure also increased common carotid artery blood flow and shear stress. However, no effects on the left ventricular ejection fraction, the production of nitric oxide and tissue plasminogen activator, or the release of endothelin-1 were found. The neurologic deficit scores of the animals were significantly lower at 24, 48, 72, and 96 hours in the enhanced external counter pulsation group, as well as at 24, 72, and 96 hours compared with animals in the control group after return of spontaneous circulation. Fewer apoptotic neurons were observed in the animals in the enhanced external counter pulsation group compared with the animals in the control and hypertension groups. CONCLUSIONS: These data indicated that the treatment of early enhanced external counter pulsation improved neurological outcome by both increasing cerebral blood flow and improving the recovery of microcirculation after return of spontaneous circulation. The treatment of early enhanced external counter pulsation can be a good option for protecting the brain after return of spontaneous circulation.
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Reanimación Cardiopulmonar/métodos , Contrapulsación/métodos , Paro Cardíaco/terapia , Animales , Presión Sanguínea , Arterias Carótidas/fisiología , Circulación Cerebrovascular/fisiología , Modelos Animales de Enfermedad , Perros , Electrocardiografía , Masculino , Óxido Nítrico/biosíntesis , Norepinefrina/farmacología , Distribución Aleatoria , Volumen SistólicoRESUMEN
The aim of this study was to investigate changes in Nogo receptor 1 (NgR(1)) expression in the cerebrum after cardiopulmonary resuscitation (CPR) in rats. Cardiac arrest was induced by alternating current in 50 SD rats through transcutaneous electrical epicardium stimulation, and CPR was performed with the Utstein mode 6 minutes after cardiac arrest. Rats were killed 1, 3, and 7 days after CPR. We performed immunofluorescence with antibodies against NgR(1) to map the distribution of NgR(1) in the rat cerebrum, whereas quantitative polymerase chain reaction was performed for quantitative analysis of NgR(1) messenger RNA (mRNA). There was a striking transient up-regulation of the NgR(1) protein and mRNA in both the hippocampus and cortex in response to CPR. Nogo receptor 1 proteins were strongly expressed in hippocampal neurons 1 and 3 days after CPR (P < .001 for 1 day and P < .05 for 3 days, vs the control group, respectively), which returned to the basal level 7 days after CPR. In the cortex, staining moderately increased 1 day after CPR and got the peak level after 3 days (P < .001), returning to normal expression levels on day 7. The levels of NgR(1) mRNA in the hippocampus and cerebral cortical cortex showed the same trend with staining. The changes were significantly different between day 3 and baseline in both the hippocampus and cortex (P < .05, respectively). Furthermore, there were significant differences between the hippocampus and cerebral cortical cortex at 1 day and 3 days after the CPR (P < .05, respectively). There was a transient increase in NgR(1) in the vulnerable areas of the rat brain after CPR. Blockade of NgR(1) may be important in maintaining the high regenerative capacity of neurons during the time window when NgR(1) expression increases.
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Reanimación Cardiopulmonar , Corteza Cerebral/metabolismo , Paro Cardíaco/terapia , Hipocampo/metabolismo , Proteínas de la Mielina/metabolismo , Receptores de Superficie Celular/metabolismo , Animales , Biomarcadores/metabolismo , Técnica del Anticuerpo Fluorescente , Proteínas Ligadas a GPI/metabolismo , Paro Cardíaco/metabolismo , Masculino , Receptor Nogo 1 , Reacción en Cadena de la Polimerasa , Ratas , Ratas Sprague-Dawley , Regulación hacia ArribaRESUMEN
BACKGROUND: To investigate the therapeutic value of enhanced external counterpulsation (EECP) on recovery of cerebral blood flow following cardiac arrest (CA) and successful resumption of spontaneous circulation (ROSC) by cardiopulmonary resuscitation. METHODS: CA models were conducted using beagle dogs induced by alternating current. After successful ROSC by cardiopulmonary resuscitation, 16 dogs were randomly divided into the EECP and control group (n = 8 per group). Dogs underwent dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging at baseline prior to CA and during the 3 days following ROSC. Mean blood pressure, right common carotid artery blood flow, intracranial microcirculation and blood lactate levels were measured. Neurological outcome was assessed by the neurologic deficit score. Hematoxylin-eosin staining and transmission electron microscopy were performed for morphology and microconstruction of the cerebral cortex. RESULTS: The EECP group exhibited a significant elevation in right common carotid artery blood flow, intracranial microcirculation and a substantial decrease in blood lactate levels relative to the control group. Relative cerebral blood flow and volume were higher in the EECP group during the 3 days. Apparent diffusion coefficients were significantly higher in the EECP group on the first and third days. After ROSC, the neurologic deficit score was significantly higher in the control group compared to those in the EECP group during the three days of experiment. The cell swelling of neurons and increase of mitochondrial mass were more pronounced in the control group. CONCLUSION: EECP is beneficial for recovery of cerebral blood flow and attenuation of ischemic cerebral edema following CA and successful ROSC.
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Reanimación Cardiopulmonar/métodos , Corteza Cerebral/irrigación sanguínea , Circulación Cerebrovascular/fisiología , Contrapulsación/métodos , Paro Cardíaco/terapia , Animales , Arteria Carótida Común/fisiología , Estudios de Casos y Controles , Corteza Cerebral/patología , Perros , Paro Cardíaco/sangre , Hemodinámica , Ácido Láctico/sangre , Imagen por Resonancia Magnética , Microcirculación/fisiología , Microscopía Electrónica de Transmisión , Distribución AleatoriaRESUMEN
Background: Adverse left ventricular remodeling after myocardial infarction (MI) compromises cardiac function and increases heart failure risk. Until now, comprehension of the role transcription factor EB (TFEB) plays after MI is limited. Objectives: The purpose of this study was to describe the effects of TFEB on fibroblasts differentiation and extracellular matrix expression after MI. Methods: AAV9 (adeno-associated virus) mediated up- and down-regulated TFEB expressions were generated in C57BL/6 mice two weeks before the MI modeling. Echocardiography, Masson, Sirius red staining immunofluorescence, and wheat germ agglutinin staining were performed at 3 days, and 1, 2, and 4 weeks after MI modeling. Fibroblasts collected from SD neonatal rats were transfected by adenovirus and siRNA, and cell counting kit-8 (CCK8), immunofluorescence, wound healing and Transwell assay were conducted. Myocardial fibrosis-related proteins were identified by Western blot. PNU-74654 (100 ng/mL) was used for 12 hours to inhibit ß-catenin-TCF/LEF1 complex. Results: The up-regulation of TFEB resulted in reduced fibroblasts proliferation and its differentiation into myofibroblasts in vitro studies. A significant up-regulation of EF and down-regulation of myocyte area was shown in the AAV9-TFEB group. Meanwhile, decreased protein level of α-SMA and collagen I were observed in vitro study. TFEB didn't affect the concentration of ß-catenin. Inhibition of TFEB, which promoted cell migration, proliferation and collagen I expression, was counteracted by PNU-74654. Conclusions: TFEB demonstrated potential in restraining fibrosis after MI by inhibiting the Wnt/ß-catenin signaling pathway.
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Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice , Infarto del Miocardio , Remodelación Ventricular , Animales , Ratones , Ratas , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , beta Catenina/genética , Colágeno Tipo I , Ratones Endogámicos C57BL , Infarto del Miocardio/genética , Vía de Señalización Wnt , Ratas Sprague-DawleyRESUMEN
Introduction: Diabetic erectile dysfunction (DMED) refers to erectile dysfunction secondary to diabetes. Erectile dysfunction is characterized by a persistent inability to achieve and maintain an erection sufficient to permit satisfactory sexual activity. Methods: Based on the Web of Science core collection database, we firstly analyzed the quantity and quality of publications in the field of DMED, secondly profiled the publishing groups in terms of country, institution, author's publication and cooperation network, and finally sorted out and summarized the hot topics of research. Results: From 2001 to 2022, a total of 1,403 articles relating to this topic were published in 359 journals. They represent the global research status, potential hotspots, and future research directions. The number of DMED-related publications and citations has steadily increased over the few past decades. Academic institutions from Europe and the United States have played a leading role in DMED research. The country, institution, journal, and author with the most publications were the United States (294), INHA University (39), the Journal of Sexual Medicine (156), and Ryu, Ji-Kan (29), respectively. The most common keywords were erectile dysfunction (796), men (256), diabetes (254), diabetes mellitus (239), prevalence (180), corpus cavernosum (171), dysfunction (155), mellitus (154), nitric-oxide synthase (153), and expression (140). The main keyword-based research topics and hotspots in the DMED field were oral sildenafil, smooth muscle relaxation, nitric oxide synthase, gene therapy, metabolic syndrome, cavernous nerve injury, stem cell, and penile prosthesis. Discussion: The terms oral sildenafil, smooth muscle relaxation, nitric oxide synthase, gene therapy, metabolic syndrome, cavernous nerve injury, stem cell, and penile prosthesis will be at the forefront of DMED-related research.
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Diabetes Mellitus Experimental , Disfunción Eréctil , Síndrome Metabólico , Masculino , Ratas , Animales , Humanos , Disfunción Eréctil/terapia , Disfunción Eréctil/complicaciones , Citrato de Sildenafil , Síndrome Metabólico/complicaciones , Ratas Sprague-Dawley , Diabetes Mellitus Experimental/metabolismo , BibliometríaRESUMEN
Introduction: Assisted reproductive technology (ART) is a method that uses various techniques to process sperm or ova. Assisted reproductive technology involves removing ova from a woman's ovaries, combining them with sperm in the laboratory, and returning them to the woman's body or donating them to another woman. Methods: Based on the web of science core collection database, we firstly analyzed the quantity and quality of publications in the field of ART, secondly profiled the publishing groups in terms of country, institution, author's publication and cooperation network, and finally sorted out and summarized the hot topics of research. Results: In total, 6,288 articles on ART were published between 2001 and 2022 in 1,013 journals. Most of these published articles represent the global research status, potential hotspots and future research directions. Publications and citations of research on assisted reproductive technology have steadily increased over the past few decades. Academic institutions in Europe and the United States have been leading in assisted reproductive technology research. The countries, institutions, journals, and authors with the most published articles were the United States (1864), Harvard Univ (108), Fertility and Sterility (819), and Stern, Judy E. (64). The most commonly used keywords are Assisted reproductive technology (3303) and in-vitro Fertilization (2139), Ivf (1140), Pregnancy (1140), Women (769), Intracytoplasmic Sperm injection (644), In Fertilization (632), Risk (545), and Outcome (423). Conclusion: Frozen embryo transfer, intracytoplasmic sperm injection, and in vitro fertilization are the main research topics and hotspots in the field of assisted reproductive technology.
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Hypothermia preconditioning (HPC) improves cardiac function after cardiac arrest, yet the mechanism is unclear. We hypothesized that HPC-activated adenosine monophosphate-activated protein kinase (AMPK) activity may be involved. Adult male Wistar rats were randomly divided into normothermia Control, HPC (cooling to 32-34°C for 30 min), and HPC + Compound C (Compound C 10 mg/kg was injected intraperitoneally 30 min before HPC group). The rats underwent 7 min of untreated ventricular fibrillation (VF) followed by cardiopulmonary resuscitation (CPR). Cardiac function and hemodynamic parameters were evaluated at 4 h after return of spontaneous circulation (ROSC). Survival status was determined 72 h after ROSC. Mechanistically, we further examined the AMPK-Unc-51 Like Autophagy Activating Kinase 1 (ULK1)-mitophagy pathway and autophagic flux in vivo and in vitro. Six of twelve rats in the Control group, 10 of 12 rats in the HPC group, and 7 of 12 rats in HPC + Compound C group were successfully resuscitated. The 72-h survival rates were 1 of 12 Control, 6 of 12 HPC, and 2 of 12 HPC + Compound C rats, respectively (P = 0.043). Rats in the HPC group demonstrated greater cardiac contractility and hemodynamic stability which were compromised by Compound C. Furthermore, HPC increased the protein levels of p-AMPKα and p-ULK1 and promoted the expression of mitochondrial autophagy-related genes. Compound C decreased the expression of mitochondrial autophagy-related genes and reduced autophagic flux. Consistent with the observations obtained in vivo, in vitro experiments in cultured neonatal rat cardiomyocytes (CMs) demonstrated that HPC attenuated simulated ischemia-reperfusion-induced CM death, accompanied by increased AMPK-ULK1-mitophagy pathway activity. These findings suggest that AMPK-ULK1-mitophagy pathway was activated by HPC and has a crucial role in cardioprotection during cardiac arrest. Manipulation of mitophagy by hypothermia may merit further investigation as a novel strategy to prevent cardiac ischemia-reperfusion injury.
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Reanimación Cardiopulmonar , Paro Cardíaco , Hipotermia Inducida , Hipotermia , Proteínas Quinasas Activadas por AMP , Animales , Masculino , Mitofagia , Ratas , Ratas WistarRESUMEN
Predicting neurological outcomes after cardiac arrest remains a major issue. This study aimed to identify novel biomarkers capable of predicting neurological prognosis after cardiac arrest. Expression profiles of GSE29540 and GSE92696 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between high and low brain performance category (CPC) scoring subgroups. Weighted gene co-expression network analysis (WGCNA) was used to screen key gene modules and crossover genes in these datasets. The protein-protein interaction (PPI) network of crossover genes was constructed from the STRING database. Based on the PPI network, the most important hub genes were identified by the cytoHubba plugin of Cytoscape software. Eight hub genes (RPL27, EEF1B2, PFDN5, RBX1, PSMD14, HINT1, SNRPD2, and RPL26) were finally screened and validated, which were downregulated in the group with poor neurological prognosis. In addition, GSEA identified critical pathways associated with these genes. Finally, a Pearson correlation analysis showed that the mRNA expression of hub genes EEF1B2, PSMD14, RPFDN5, RBX1, and SNRPD2 were significantly and positively correlated with NDS scores in rats. Our work could provide comprehensive insights into understanding pathogenesis and potential new biomarkers for predicting neurological outcomes after cardiac arrest.
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OBJECTIVE: To examine the changes in PECAM-1 expression and its correlation to the level of pulmonary tissue injury in the lungs from rabbits exposed to acute PQ poisoning. METHODS: Three groups of New Zealand rabbits (12 each, randomly assigned) were treated with PQ at 8, 16 and 32 mg/kg respectively through gavage. The animals were sacrificed 7 days after the poisoning and the upper lobe of their lungs collected for semi-quantitative microscopic evaluation of tissue injury, pulmonary fibrosis and the expression of PECAM-1 after hematoxylin-eosin (HE), Masson, and immuno-histological staining. The correlation analysis was used for the relationship between the expression of PECAM-1 and lung injury score or fibrosis of lung. RESULTS: The evaluation scores (demonstrated as mean+ standard deviation) in the three treatment groups were found to be (a) 8.33±1.03, 9.83±1.17 and 11.50±1.38 for lung tissue injury, (b) (31.09±2.05)%, (34.37±1.62)% and (36.54±0.44)% for pulmonary fibrosis, and (c) (20.31± 0.70)%, (19.34±0.68)% and (18.37±0.46)% for PECAM-1 expression. Statistically significant difference (P< 0.05) was found between the results from different dose groups for all the indexes examined. Pearson correlation analysis showed that expression of PECAM-1 was negatively correlated to lung injury score ( r = - 0.732, P = 0.001) and fibrosis degree of lung ( r = - 0. 779, P< 0.001). CONCLUSION: (1) The expressions of PECAM-1 in the lungs of PQ treated animals decrease to increased dose of PQ poisoning, (2) such decrease is correlated to the degree of pulmonary tissue injury and fibrosis of lung. It is possible that PECAM-1 expression inhibition be an important factor in the development of lung injury after acute PQ poisoning.
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Pulmón/patología , Paraquat/envenenamiento , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Animales , Modelos Animales de Enfermedad , Femenino , Pulmón/metabolismo , Lesión Pulmonar/metabolismo , Masculino , ConejosRESUMEN
Cartilage acidic protein 1 (CRTAC1) is predicted to be aberrantly expressed in bladder cancer based on bioinformatics analysis. However, its functions and molecular mechanism in bladder cancer remain elusive. This study aimed to explore the role of CRTAC1 in bladder cancer. The mRNA and protein levels of CRTAC1 and Yin Yang 1 (YY1) were detected by reverse transcription quantitative polymerase chain reaction and western blotting. We found that CRTAC1 was downregulated in bladder cancer tissues and cells. Cell Counting Kit-8 assays, colony formation assays, wound healing assays and Transwell assays and western blotting revealed that CRTAC1 overexpression inhibited cell viability, proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process in bladder cancer, while CRTAC1 knockdown exerted opposite effects on these malignant behaviors. Mechanistically, CRTAC1 targeted YY1 in bladder cancer cells. YY1 was upregulated in bladder cancer tissues and cells. CRTAC1 negatively modulated the mRNA and protein expression of YY1 in bladder cancer cells. Co-localization of CRTAC1 and YY1 expression was assessed using immunofluorescence staining and Co-Immunoprecipitation assays. The interaction between CRTAC1 and YY1 was explored by Chromatin immunoprecipitation and luciferase reporter assays. Moreover, CRTAC1 inactivated the TGF-ß pathway by downregulating YY1 expression. Protein levels of factors associated with the TGF-ß pathway were examined by western blotting. Rescue assays indicated that CRTAC1 inhibited malignant behaviors of bladder cancer cells by targeting YY1. Overall, CRTAC1 inhibited malignant phenotypes of bladder cancer cells by targeting YY1 to inactivate the TGF-ß pathway.