RESUMEN
A new compound xylarkarynone A (1), a first reported natural product compound xylarkarynone B (2) and eight known compounds (3-10) were isolated from Xylaria sp. HHY-2. Their structures were elucidated by spectroscopic methods, DP4+ probability analyses and electronic circular dichroism (ECD) calculations. The bioactivities of isolated compounds were assayed. Compound 1 exhibited obvious activity against A549 cells with an IC50 value of 6.12±0.28â µM. Additionally, compound 1 showed moderate antifungal activities against Plectosphaerella cucumerina and Aspergillus niger with minimum inhibitory concentrations (MICs) of both 16â µg/mL, which was at the same grade with positive control nystatin. Most compounds exhibited varying degrees of inhibitory activity against P. cucumerina, indicating that Xylaria sp. has potential as inhibitors against P. cucumerina.
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Antifúngicos , Aspergillus niger , Pruebas de Sensibilidad Microbiana , Sesquiterpenos , Xylariales , Humanos , Xylariales/química , Antifúngicos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Sesquiterpenos/química , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , Aspergillus niger/efectos de los fármacos , Células A549 , Ensayos de Selección de Medicamentos Antitumorales , Ascomicetos/química , Estructura Molecular , Conformación Molecular , Relación Estructura-Actividad , Relación Dosis-Respuesta a DrogaRESUMEN
The fungus Nectria sp. MHHJ-3 was isolated from Illigera rhodantha. A molecular networking-guided the secondary metabolites investigation of Nectria sp. MHHJ-3 led to the isolation of ten metabolites (1-10), including two new naphthalenone derivatives, nectrianaphthalenones A (1) and B (2), and two new steroids, nectriasteroids A (3) and B (4). Their structures were elucidated by extensive spectroscopic analysis including the HRESIMS, 1D/2D NMR and electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for 1-2 was proposed. Compounds 1 and 2 exhibited moderate acetylcholinesterase (AChE) inhibitory activities. Compounds 3 and 4 showed significant cytotoxic activity against selected tumor cells. Particularly, compound 3 exhibited the strongest activity against A549 cells with an IC50 value of 13.73 ± 0.03 µM, which was at the same grade with that of positive control cisplatin.
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Antineoplásicos , Nectria , Estructura Molecular , Nectria/química , Acetilcolinesterasa , Hongos , Antineoplásicos/farmacologíaRESUMEN
OBJECTIVE(S): The prognostic value of systemic cytokine profiles and inflammatory markers in colorectal cancer were explored by several studies. We want to know more about inflammatory biomarkers in colorectal adenoma and early cancer. METHOD: The level of 38 inflammatory markers in the plasma of 112 adenoma patients, 72 Tis-T1 staging of colorectal carcinoma patients, 34 T2-T4 staging of colorectal carcinoma patients and 53 normal subjects were detected and compared. RESULT(S): Eight inflammatory biomarkers (Eotaxin, GCSF, IL-4, IL-5, IL-17E, MCP-1, TNF-α and VEGF-A) have higher plasma concentrations in colorectal adenoma and cancer patients compared with normal participants over 50 years old. CONCLUSION(S): Inflammatory markers may have the prognostic value for colorectal adenoma and early-stage carcinoma.
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Adenoma , Neoplasias Colorrectales , Humanos , Persona de Mediana Edad , Neoplasias Colorrectales/patología , Biomarcadores , Factor de Necrosis Tumoral alfa , Pronóstico , Biomarcadores de TumorRESUMEN
The fungus Pseudopestalotiopsis theae isolated from the fresh leaves of Illigera celebica, has been reported to be a pathogenic fungus that can cause gray blight on tea leaves, a disease characterized by the appearance of necrotic lesions on tea leaves. The pathogenic substances in this fungus have not been clearly identified. Considering the possible involvement of specialized metabolites in symptom appearance, a chemical investigation of specialized metabolites on P. theae was conducted, resulting in the isolation of eight meroterpenoids, including six undescribed biscognienynes G-L and two known ones (biscognienynes B and D). The structures of these new compounds were characterized by extensive NMR spectroscopic and HR-ESI-MS data, and their absolute configurations were elucidated by ECD calculations. Except for biscogniyne L, all the isolated biscognienynes showed different degrees of phytotoxicity to tea in vivo, thereby revealing for the first time the substances in P. theae that cause tea gray blight. Inspired by the fact that phytotoxins produced by pathogenic fungus are an effective resource for designing natural and safe bioherbicides, when assayed the herbicidal activity through Petri dish bioassays, biscognienynes G-J showed phytotoxic effects against seed germination and seedling growth of Setaria viridis, strongly inhibiting seed germination percentage and radicle and germ lengths of seedlings. The results of this study demonstrated the great potential of biscognienynes G-J to be proposed and developed as ecofriendly herbicides.
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Ascomicetos , Herbicidas , Herbicidas/farmacología , Herbicidas/química , Ascomicetos/química , Plantones , TéRESUMEN
A new cyclopentenone derivative, atrovinol (1), together with ten known compounds (2-11) were isolated from Trichoderma atroviride HH-01, an endophytic fungus from Illigera rhodantha (Hernandiaceae). Their structures were identified by HRESIMS, 1 D/2D NMR, and electronic circular dichroism (ECD) spectra. Compound 1 exhibited moderate inhibitory activity against Staphylococcus aureus and Bacillus subtilis with MIC values of 8.0 µg/mL and 16.0 µg/mL, respectively.
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Hypocreales , Trichoderma , Estructura Molecular , Ciclopentanos/farmacología , Ciclopentanos/química , Trichoderma/química , Antibacterianos/químicaRESUMEN
A new highly oxygenated polyketide derivative, trichodersine (1), together with fourteen known compounds (2-15) were isolated from Trichoderma sp. MWTGP-04. The structure of trichodersine (1) was established based on comprehensive spectroscopic data analysis, and biogenesis argument. The results of double culture experiments indicated that the strain exhibited potential antifungal activity. The antifungal activities of all isolated compounds were evaluated, among them compound 1 exhibited remarkable antifungal activities against Fusarium solani, Plectosphaerella cucumerina, Alternaria panax, and Aspergillus niger, with minimum inhibitory concentrations (MICs) of 4, 4, 16, and 32â µg/mL, respectively. In addition, the antifungal experiments of polyketide derivatives (1-3) disclosed that their degree of oxidation was a key factor affecting the antifungal activity.
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Policétidos , Trichoderma , Antifúngicos/química , Trichoderma/química , Policétidos/farmacología , Aspergillus niger , Pruebas de Sensibilidad MicrobianaRESUMEN
A new cyclohexenone derivative, phomopine (1), together with five known compounds (2-6) were isolated from Phomopsis sp. XM-01. The structure of 1 was determined by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculation. In vitro bioassays, compounds 1 and 2 exhibited potent antimicrobial activities against Candida albicans and Staphylococcus aureus with their corresponding minimum inhibitory concentrations (MICs) of 64 µg/mL and 16 µg/mL, respectively.
RESUMEN
Seven previously undescribed compounds were isolated from the endophytic fungus Annulohypoxylon sp. KYG-19 (family Xylariaceae), including three gymnomitrane-type sesquiterpenes xylariacinols A, B, and D (1, 2, and 4), one bisabolane-type sesquiterpene annulnol F (6), one phenol derivative lariacinol G (7), and two polyhydroxy compounds hypoxylonols H and I (8 and 9), together with two known gymnomitrane-type sesquiterpenes emericellin A (3) and 3-gymnomitren-15-ol (5). The assignments of their structures was determined by extensive spectroscopic and spectrometric analysis, acetonide analysis, Mosher's method, and X-ray crystallography. In addition, the structures of emericellins A and B, which were reported to possess an unprecedented tricyclo[4, 4, 2, 1]hendecane scaffold, were revised by comparing their spectroscopic data with those of 1 and 3. Compounds 1 and 4 exhibited antibacterial activity against Escherichia coli with minimum inhibitory concentrations of 4 and 2 µg/mL, respectively.
Asunto(s)
Sesquiterpenos , Xylariales , Antibacterianos/farmacología , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Sesquiterpenos/química , Xylariales/químicaRESUMEN
BACKGROUND: Complex regional pain syndrome (CRPS) is a rare and severe chronic pain condition, with effective treatment options not established for many patients. The underlying pathophysiology remains unclear, but there is a growing appreciation for the role of central mechanisms which have formed the basis for brain-based therapies such as transcranial magnetic stimulation and mirror visual feedback (MVF). MVF has been deployed in the treatment of CRPS using both conventional mirrors and virtual reality (VR). OBJECTIVE: The aim of this study was to further investigate the use of VR in the treatment of patients with unilateral upper limb CRPS. VR has the potential advantage of more flexible and more motivating tasks, as well as the option of tracking patient improvement through the use of movement data. METHODS: We describe the development, acceptability, feasibility, and usability of an open-source VR program MVF module designed to be used with consumer VR systems for the treatment of CRPS. The development team was an interdisciplinary group of physical therapists, pain researchers, and VR researchers. Patients recruited from a pain clinic completed 3-5 visits each to trial the system and assessed their experiences in pre- and post-treatment questionnaires. RESULTS: All 9 (100%) participants were able to use the system for 3, 4, or 5 trials each. None of the participants quit any trial due to cybersickness. All 9 (100%) participants reported interest in using the module in the future. Participants' reported average pain scores in the affected limb were not significantly different from baseline during treatment or after treatment (P=.16). We did not find a statistically significant effect on participants' self-reported average pain scores. CONCLUSIONS: We propose that this module could be a useful starting point for modification and testing for other researchers. We share modifications to make this module usable with standalone headsets and finger tracking. Next steps include adapting this module for at-home use, or for use with participants with lower limb pain.
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Síndromes de Dolor Regional Complejo , Realidad Virtual , Síndromes de Dolor Regional Complejo/terapia , Estudios de Factibilidad , Retroalimentación Sensorial , Humanos , Proyectos PilotoRESUMEN
Background: Coronavirus Disease 2019 (COVID-19) caused by a novel strain of coronavirus (SARS-CoV-2) posed a major threat to public health. Anesthesiologists and operating room (OR) nurses are at high risk of occupational exposure to SARS-CoV-2 and developing COVID-19. We conducted a single-center survey to investigate the psychological status and perceived social support among operation room (OR) medical staffs during the outbreak of Coronavirus Disease 2019 (COVID-19). Methods: A total of 197 OR medical staffs were enrolled in the survey. The authors performed a cohort study during the period of Wuhan lockdown and then conducted a longitudinal follow-up after lifting of lockdown. The Patient Health Questionaire-9 (PHQ-9) was used to assess for depression and Generalized Anxiety Disorder-7 (GAD-7) for anxiety. The Multidimensional Scale of Perceived Social Support (MSPSS) was used to assess perceived social support. We compared the psychological status of OR medical staffs before and after lifting of Wuhan lockdown. Results: During the period of city lockdown, 177 (89.8%) had close contact with confirmed COVID-19 cases. The prevalence of depression and anxiety in OR medical staffs was 41.6 and 43.1% under Wuhan lockdown, while 13.2 and 15.7% after lifting of lockdown (P = 0.002, P = 0.004). Logistic regression analysis showed that being female, living in suburb areas, shortage of protective equipment and close contact with COVID-19 patients were associated with a higher risk of depression and anxiety. Perceived social support was negatively correlated with depression and anxiety severity in the OR medical staffs (P < 0.05). Conclusions: OR medical staffs exhibited high incidence of anxiety and depression faced with the high risk of exposure to COVID-19 patients. More social support and social recognition for anesthesiologists and OR nurses might potentially help them relieve their psychological pressure.
RESUMEN
BACKGROUND: Activation of microglia is involved in a broad range of neuroinflammatory diseases. Suppression of microglial activation may, therefore, contribute to alleviate the progression of neuroinflammatory diseases. It has been reported that propofol has a potent anti-inflammatory property. In the present study, we investigated the effects of posttreatment with propofol on the production of inflammatory molecules in lipopolysaccharide (LPS)-stimulated microglia. MATERIALS AND METHODS: Microglia were exposed to various concentrations (25, 50, 100, 250 µM) of propofol for 1 h after LPS stimulation for 24 h. The levels of proinflammatory mediators inducible nitric oxide synthase (iNOS)/nitric oxide (NO), cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were measured. RESULTS: Propofol at a concentration of 25 µM did not affect the production of proinflammatory mediators, which was enhanced by LPS. At the concentrations of 50, 100, and 250 µM, propofol significantly inhibited LPS-mediated production of NO, PGE2, TNF-α, and IL-1ß and the expression of iNOSmRNA, COX-2mRNA, TNF-α mRNA, and IL-1ß mRNA. CONCLUSIONS: These results suggest that propofol, at clinically relevant concentrations, can reduce inflammatory responses in LPS-induced inflammation in activated microglia and might be an intravenous anesthetic of choice when patients with neuroinflammatory diseases require sedation and/or general anesthesia.
Asunto(s)
Mediadores de Inflamación/fisiología , Lipopolisacáridos/farmacología , Microglía/inmunología , Fármacos Neuroprotectores/farmacología , Propofol/farmacología , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Ciclooxigenasa 2/genética , Citocinas/fisiología , Relación Dosis-Respuesta a Droga , Óxido Nítrico/biosíntesis , Ratas , Regulación hacia ArribaRESUMEN
BACKGROUND: Heme oxygenase-1 (HO-1) has been shown to have antioxidant and anti-apoptotic properties. The present study transduced HO-1 protein into intestinal tissues using PEP-1, a cell-penetrating peptide, and investigated its potentiality in prevention against intestinal ischemia/reperfusion (I/R) injury. MATERIALS AND METHODS: PEP-1-HO-1 fusion protein was administered intravenously to explore the time and dose characteristics through measuring serum HO-1 levels. Twenty-four male Sprague-Dawley rats were randomly divided into three groups: sham, intestinal I/R (II/R), II/R + PEP-1-HO-1 fusion protein (HO). The model was established by occluding the superior mesenteric artery for 45 min followed by 120 min reperfusion. In HO group, PEP-1-HO-1 was administered intravenously 30 min before ischemia, whereas animals in sham and II/R groups received the equal volume of physiological saline. After the experiment, the intestines were harvested for determination of histologic injury, wet/dry ratio, enzyme activity, apoptosis, and His-probe protein (one part of PEP-1-HO-1). RESULTS: Levels of serum HO-1 were dose- and time-dependent manner after intravenous injection of PEP-1-HO-1. I/R caused deterioration of histologic characteristics and increases in histologic injury scoring, wet/dry ratio, myeloperoxidase activity, malondialdehyde, and intestinal apoptosis. These changes were also accompanied by a decrease in superoxide dismutase activity (P < 0.05). PEP-1-HO-1 treatment significantly reversed these changes (P < 0.05). Furthermore, His-probe protein expression was only detected in PEP-1-HO-1-treated animals. CONCLUSION: Treatment of PEP-1-HO-1 attenuates intestinal I/R injury, which might be attributable to its antioxidant and anti-apoptotic roles of HO-1.
Asunto(s)
Hemo-Oxigenasa 1/sangre , Hemo-Oxigenasa 1/genética , Intestinos/irrigación sanguínea , Proteínas Recombinantes de Fusión/sangre , Proteínas Recombinantes de Fusión/genética , Daño por Reperfusión/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Inyecciones Intravenosas , Intestinos/patología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Malondialdehído/metabolismo , Tamaño de los Órganos , Peroxidasa/metabolismo , Fenoles/sangre , Extractos Vegetales/sangre , Extractos Vegetales/genética , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/patologíaRESUMEN
BACKGROUND: Postoperative cognitive dysfunction, a common complication after surgery in elderly patients, is an increasing and largely underestimated problem without a defined etiology. Neuroinflammation plays an important role in the pathogenesis of postoperative cognitive dysfunction. The present study sought to investigate the role of neuroinflammation mediated by high-mobility group box 1 (HMGB1), S100B, and the receptor for advanced glycation end product (RAGE) in cognitive dysfunction after partial hepatectomy in aged mice. MATERIALS AND METHODS: Old C57BL/6 mice were randomly divided into three groups: normal control (n = 18), anesthetic (n = 66), and surgery (n = 66). The mice in the surgery or anesthetic group received isoflurane anesthesia for either partial hepatectomy or no surgery, respectively. Cognitive function was subsequently assessed using a Y-maze. HMGB1, S100B, RAGE, interleukin-1ß, and nuclear factor-kappaB p65 levels were measured at 12 h and 1, 3, and 7 d after surgery. Immunofluorescence double labeling was performed to study the colocalization between RAGE and its ligands, HMGB1 and S100B. RESULTS: The mice's learning and memory abilities were significantly impaired at 1 and 3 d and 2 and 4 d after surgery, respectively. The expression of HMGB1, S100B, RAGE, and nuclear factor-kappaB p65 had increased significantly at 12 h and 1 and 3 d after surgery. The interleukin-1ß level was significantly increased at 1 and 3 d after surgery. The interaction of HMGB1 or S100B with RAGE was confirmed at 1 d after surgery. CONCLUSIONS: These data suggest that HMGB1, S100B, and RAGE signaling modulate the hippocampal inflammatory response and might play key roles in surgery-induced cognitive decline.
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Trastornos del Conocimiento/inmunología , Proteína HMGB1/inmunología , Neuritis/inmunología , Complicaciones Posoperatorias/inmunología , Receptores Inmunológicos/inmunología , Subunidad beta de la Proteína de Unión al Calcio S100/inmunología , Envejecimiento/inmunología , Envejecimiento/metabolismo , Animales , Astrocitos/inmunología , Trastornos del Conocimiento/etiología , Proteína HMGB1/metabolismo , Hepatectomía/efectos adversos , Interleucina-1beta/inmunología , Interleucina-1beta/metabolismo , Masculino , Aprendizaje por Laberinto , Memoria , Ratones , Ratones Endogámicos C57BL , Neuritis/etiología , Neuroinmunomodulación/inmunología , Complicaciones Posoperatorias/etiología , Distribución Aleatoria , Receptor para Productos Finales de Glicación Avanzada , Receptores Inmunológicos/metabolismo , Subunidad beta de la Proteína de Unión al Calcio S100/metabolismoRESUMEN
Recent studies have uncovered that overexpression of heme oxygenase-1 (HO-1) by induction or gene transfer provides myocardial protection. In the present study, we investigated whether HO-1 protein mediated by cell-penetrating peptide PEP-1 could confer cardioprotection in a rat model of myocardial ischemia/reperfusion (I/R) injury. Male Sprague-Dawley rats were subjected to 30 minutes of ischemia by occluding the left anterior descending coronary artery and to 120 minutes of reperfusion to prepare the model of I/R. Animals were randomized to receive PEP-1-HO-1 fusion protein or saline 30 minutes before a 30-minute occlusion. I/R increased myocardial infarct size and levels of malondialdehyde, serum tumor necrosis factor alpha, and interleukin 6 and reduced myocardial superoxide dismutase activity. Administration of PEP-1-HO-1 reduced myocardial infarct size and levels of malondialdehyde, serum tumor necrosis factor alpha, and interleukin 6 and increased myocardial superoxide dismutase and HO-1 activities. His-probe protein was only detected in PEP-1-HO-1-transduced hearts. In addition, transduction of PEP-1-HO-1 markedly reduced elevated myocardial tissue nuclear factor-κB induced by I/R. The results suggested that transduction of PEP-1-HO-1 fusion protein decreased myocardial reperfusion injury, probably by attenuating the production of oxidants and proinflammatory cytokines regulated by nuclear factor-κB.
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Hemo-Oxigenasa 1/metabolismo , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/fisiopatología , FN-kappa B/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Animales , Modelos Animales de Enfermedad , Hemo-Oxigenasa 1/administración & dosificación , Interleucina-6/metabolismo , Masculino , Malondialdehído/metabolismo , Infarto del Miocardio/patología , Ratas , Ratas Sprague-Dawley , Proteínas Recombinantes de Fusión/administración & dosificación , Superóxido Dismutasa/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Neuroinflammation mediated by microglia has been implicated in delirium. Suppression of microglial activation may therefore contribute to alleviate delirium. It has been reported that dexmedetomidine (DEX) has a potent anti-inflammatory property. In the present study, we investigated the effects of DEX on the production of proinflammatory mediators in lipopolysaccharide-stimulated microglia. MATERIALS AND METHODS: The concentrations of DEX were chosen to correspond to 1, 10, and 100 times of clinically relevant concentration (i.e., 1, 10, and 100ng/mL). The levels of proinflammatory mediators, such as inducible nitric oxide synthase or nitric oxide, prostaglandin E(2), interleukin 1ß, and tumor necrosis factor α, were measured. RESULTS: DEX at 1ng/mL did not affect the production of proinflammatory mediators. DEX at 10 and 100ng/mL significantly inhibited the release of nitric oxide, prostaglandin E(2), interleukin 1ß, and tumor necrosis factor α and the expression of inducible nitric oxide synthase messenger RNA. CONCLUSIONS: These results suggest that DEX is a potent suppressor of lipopolysaccharide-induced inflammation in activated microglia and may be a potential therapeutic agent for the treatment of intensive care unit delirium.
Asunto(s)
Antiinflamatorios/uso terapéutico , Dexmedetomidina/uso terapéutico , Inflamación/inducido químicamente , Inflamación/prevención & control , Lipopolisacáridos/efectos adversos , Microglía/metabolismo , Animales , Antiinflamatorios/farmacología , Biomarcadores/metabolismo , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Dexmedetomidina/farmacología , Dinoprostona/metabolismo , Relación Dosis-Respuesta a Droga , Inflamación/metabolismo , Interleucina-1beta/metabolismo , Lipopolisacáridos/farmacología , Microglía/efectos de los fármacos , Microglía/patología , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
BACKGROUND: Neuroinflammatory response triggered by surgery has been increasingly reported to be associated with postoperative cognitive dysfunction. Proinflammatory cytokines, such as interleukin 1ß (IL-1ß) and tumor necrosis factor α (TNF-α), play a pivotal role in mediating surgery-induced neuroinflammation. The role of cyclooxygenase-2 (COX-2), a critical regulator in inflammatory response, in surgery-induced neuroinflammation is still unknown. The aim of the study was to investigate the changes of COX-2 expression and prostaglandin E2 (PGE2) production in the hippocampus in aged rats following partial hepatectomy. The effects of selective COX-2 inhibitor (parecoxib) on hippocampal proinflammatory cytokine expression were also evaluated. METHODS: Aged rats were randomly divided into three groups: control (n = 10), surgery (n = 30), and parecoxib (n = 30). Control animals received sterile saline to control for the effects of injection stress. Rats in the surgery group received partial hepatectomy under isoflurane anesthesia and sterile saline injection. Rats in the parecoxib group received surgery and anesthesia similar to surgery group rats, and parecoxib treatment. On postanesthetic days 1, 3, and 7, animals were euthanized to assess levels of hippocampal COX-2 expression, PGE2 production, and cytokines IL-1ß and TNF-α expression. The effects of parecoxib on proinflammatory cytokine expression were also assessed. RESULTS: Partial hepatectomy significantly increased COX-2 expression, PGE2 production, and proinflammatory cytokine expression in the hippocampus in aged rats on postoperative days 1 and 3. Parecoxib inhibited hippocampal IL-1ß and TNF-α expression through downregulation of the COX-2/PGE2 pathway. CONCLUSION: COX-2 may play a critical role in surgery-induced neuroinflammation. The COX-2 inhibitor may be a promising candidate for treatment of neuroinflammation caused by surgical trauma.
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Trastornos del Conocimiento/prevención & control , Inhibidores de la Ciclooxigenasa 2/farmacología , Encefalitis/prevención & control , Isoxazoles/farmacología , Complicaciones Posoperatorias/prevención & control , Envejecimiento/inmunología , Animales , Trastornos del Conocimiento/tratamiento farmacológico , Trastornos del Conocimiento/inmunología , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/inmunología , Dinoprostona/inmunología , Dinoprostona/metabolismo , Encefalitis/tratamiento farmacológico , Expresión Génica/inmunología , Hipocampo/efectos de los fármacos , Hipocampo/inmunología , Hipocampo/cirugía , Interleucina-1beta/genética , Interleucina-1beta/inmunología , Masculino , Complicaciones Posoperatorias/tratamiento farmacológico , Complicaciones Posoperatorias/inmunología , Ratas , Ratas Sprague-Dawley , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
OBJECTIVE: To investigate the effect of rat heme oxygenase-1 (rHO-1) gene carried by recombinant adeno-associated virus (rAAV) on myocardial ischemia/reperfusion (I/R) injury in rats. METHODS: Ninety-five healthy male Sprague-Dawley (SD) rats weighing 225-250 g were randomly divided into four groups: sham operation group (I, n=8); normal saline group (II, n=29); rAAV-EGFP (enhanced green fluorescent protein) group (III, n=29) and rAAV-rHO-1 group (IV, n=29). In II, III and IV groups, 600 mul of normal saline, rAAV-EGFP or rAAV-rHO-1 was injected intra-myocardial at four sites on the anterior and posterior walls of left ventricle. After 3 months, 3 animals in each group were sacrificed. EGFP-expression in heart sections was observed under fluorescence microscope. The expression of HO-1 in the injected myocardium was detected by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). The remaining animals in the four groups were anesthetized, tracheostomized and mechanically ventilated. I/R of myocardium was producing by blocking the left anterior descending branch of coronary artery (LAD) for 30 minutes followed by 120 minutes reperfusion. After the successful reproduction of the model, the animals were killed and their hearts were harvested for determination of myocardial infarct size, apoptotic index (AI), and pathology changes in myocardial tissue. RESULTS: The expression of EGFP was detected in group III only, and transfection efficiency was (53.5+/-2.0)%. AI was significantly higher in group II, group III and group IV than in group I (all P<0.01). The expression of HO-1 mRNA and protein was significantly higher, and the infarct size and AI were significantly lower in group IV than in group II and group III (all P<0.01). The degree of damage to myocardial tissue was significantly severer in group II and group III than in group I and group IV. There was no significant difference between group II and group III. CONCLUSION: rAAV-mediated rHO-1 gene transfection may attenuate myocardium I/R injury by inhibiting apoptosis of cardiomyocyte in rats.
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Hemo-Oxigenasa 1/genética , Daño por Reperfusión Miocárdica/patología , Miocitos Cardíacos/patología , Animales , Apoptosis , Dependovirus/genética , Modelos Animales de Enfermedad , Hemo-Oxigenasa 1/metabolismo , Masculino , Daño por Reperfusión Miocárdica/metabolismo , Miocardio/metabolismo , Miocardio/patología , Miocitos Cardíacos/metabolismo , ARN Mensajero/genética , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , TransfecciónRESUMEN
Nuclear factor kappa B (NF-kappaB) plays a central role in regulating the transcription of several genes associated with sepsis/septic shock. Therefore, the author investigated the effects of propofol on the plasma tumor necrosis factor alpha and interleukin 6 (TNF-alpha and IL-6) levels and NF-kappaB activation during polymicrobial sepsis in rats. Male Sprague-Dawlay rats were subjected to cecal ligation and puncture (CLP, a model of polymicrobial sepsis) or sham operation. The animals were randomly assigned into four equal groups (n = 10): sham CLP group, CLP group, PPF (propofol) I group and PPF II group. Thirty minutes before CLP, propofol (5 and 10 mg kg(-1) h(-1), respectively) was infused continuously through the left femoral vein cannula in PPF I group or PPF II group, CLP group and sham CLP group receiving 0.9% saline only at the rates of 5 ml kg(-1) h(-1). The right femoral artery was cannulated to monitor mean arterial pressure (MAP) and heart rates (HR). CLP produced progressive hypotension and a first increase followed by a decrease in HR. The plasma TNF-alpha and IL-6 levels and the hepatic NF-kappaB activation significantly increased after CLP alone. Compared with CLP group, propofol treatment reversed hypotension, slightly steadied heartbeats, and decreased the plasma TNF-alpha and IL-6 levels, and significantly suppressed NF-kappaB activation. Propofol has inhibited the hepatic NF-kappaB activation and the pro-inflammatory cytokine response during polymicrobial sepsis in rats.
Asunto(s)
Citocinas/sangre , FN-kappa B/sangre , Propofol/farmacología , Sepsis/sangre , Animales , Ciego/microbiología , Ciego/cirugía , Modelos Animales de Enfermedad , Hemodinámica/efectos de los fármacos , Conducto Hepático Común/patología , Histocitoquímica , Interleucina-6/sangre , Ligadura , Masculino , Peritonitis/sangre , Peritonitis/microbiología , Ratas , Ratas Sprague-Dawley , Sepsis/microbiología , Sepsis/patología , Factor de Transcripción ReIA/sangre , Factor de Necrosis Tumoral alfa/sangreRESUMEN
Shenfu injection (the major components of which are ginsenosides compound, extract of Panax ginseng shown to have antioxidant properties) is a well-known important Chinese traditional medicine used for the treatment of various diseases especial for cardiac diseases. The precise mechanism of the biological actions of this plant is not fully understood, in order to elucidate the protection of cardiomyocytes. The aim of the present study was to investigate the effect of Shenfu injection on hypoxia/reoxygenation (H/R)-induced apoptosis and the expression of bcl-2 and caspase-3 in cultured neonatal rat cardiomyocytes in vitro. Ventricular myocytes were isolated from neonatal rat hearts and were exposed to 4 h of hypoxia followed by 16 h of reoxygenation. The results indicated that treatment with different doses of Shenfu injection protected cardiacmyocyte cultures from hypoxia/reoxygenation-induced apoptosis. Caspase-3 activation was decreased in hypoxic/reoxygenationed cardiomyocytes co-treated with Shenfu injection when compared to hypoxia/reoxygenation alone treated cultures. Expression of the Bcl-2 proteins was increased in Shenfu injection-treated cardiomyocytes subjected to hypoxia/reoxygenation. In conclusion, ginsenosides compound has obviously protective effects on cardiacmyocytes against apoptosis induced by hypoxia/reoxygenation injury, whose mechanisms probably involve the inhibition of down-regulation of Bcl-2 protein levels and sequential activation of caspase-3.
Asunto(s)
Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Hipoxia/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Animales , Animales Recién Nacidos , Cardiotónicos , Caspasa 3/efectos de los fármacos , Caspasa 3/metabolismo , Células Cultivadas , Medicamentos Herbarios Chinos/administración & dosificación , Ventrículos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Oxígeno , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos , RatasRESUMEN
OBJECTIVE: The effects of resveratrol treatment on ventricular arrhythmia, survival, and late cardiac remodeling were evaluated in rats with myocardial infarction (MI). METHODS: Three groups of rats (S: ham-operated, MI, and MI pre-treated with resveratrol) were treated in an in vivo MI model by ligation of left anterior descending coronary artery. The electrocardiogram signals were monitored and recorded for 24 h using an implanted telemetry transmitter. The incidence of ventricular arrhythmias during the first 24-h after MI was also evaluated. Meanwhile, invasive in vivo electrophysiology with pacing in the right ventricle was performed in each group to assess the inducibility of ventricular arrhythmias. RESULTS: Administration of resveratrol significantly suppressed the MI-induced ventricular tachycardia and ventricular fibrillation (0.4 +/- 0.2 in Resv group vs. 7.1 +/- 2.2 in MI group episodes per hour per rat, P < 0.01). Data also showed that the incidence of inducible ventricular tachycardia was lower in the Resv group than the MI group (46% vs. 81%, P < 0.01). The infarct size and mortality in the Resv group at 14 weeks were reduced by 20% and 33%, respectively, compared with the MI groups. Results from patch clamp recording revealed that resveratrol inhibited L-type calcium current (I (Ca-L)), and selectively enhanced ATP-sensitive K(+) current (I (K,ATP)) in a concentration-dependent manner. CONCLUSION: These results suggested that the emerging anti-arrhythmic character induced by resveratrol treatment in rat hearts could be mainly accounted for by inhibition of I (Ca-L) and enhancement of I (K,ATP). Administration of resveratrol also improved the long-term survival by suppressing left ventricular remodeling.