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BACKGROUND: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). METHODS: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD's causal effects on the relative abundances of specific features of the gut microbiome. RESULTS: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. CONCLUSION: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.
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Microbioma Gastrointestinal , Trastornos por Estrés Postraumático , Humanos , Trastornos por Estrés Postraumático/genética , Estudio de Asociación del Genoma Completo , Reproducibilidad de los Resultados , Suplementos DietéticosRESUMEN
Objective: To investigate the effect of microRNA-8126 (miR-8126) on isoflurane-induced hippocampal neurotoxicity in rats. Methods: A rat isoflurane nerve injury model was constructed. The expression of miR-8126 in the hippocampal region of normal and injured rats was measured by qRT-PCR; synaptic density protein-95, PAK-3 (p21-activated kinase-3) and apoptosis-related proteins cytochrome C, cleaved caspase-3, and cleaved PARP were detected by Western blot. The Cytochrome C, cleaved-caspase-3, and cleaved PARP expression was detected by WB, as well as GSH-Px, CAT, SOD, and ROS. Results: miR-8126 was lowly expressed in the isoflurane-treated rat hippocampal region and in rat hippocampal neuronal cells, and the expression of apoptosis-related proteins and apoptosis levels were significantly increased, and neural activity, cell activity, and proliferation capacity were significantly decreased. Oxidative stress levels and ROS content were significantly increased; overexpression of miR-8126 in the rat hippocampal region significantly inhibited oxidative stress and apoptosis. Overexpression of miR-8126 in rat hippocampal neural progenitor cells significantly increased cell activity, proliferative capacity, and significantly smaller mitochondrial size and it decreased ROS content and oxidative stress levels and apoptosis-related protein expression compared to isoflurane-treated cells; while inhibition of miR-8126 expression in rat hippocampal neuronal cells significantly decreased cell activity, proliferative capacity, and mitochondrial size compared to the control group. In contrast, inhibition of miR-8126 expression in rat hippocampal neuronal cells resulted in a further decrease in cell activity, proliferation capacity, and significantly larger mitochondrial size and increased expression of apoptosis-related proteins compared with the control group. miR-8126 regulates the activity of rat hippocampal neuronal cells by targeting ATF4. Conclusions: miR-8126 attenuates isoflurane-induced hippocampal neurotoxicity in rats by mediating antioxidative stress.
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Taurochenodeoxycholic acid (TCDCA) is one of the main effective components of bile acid, playing critical roles in apoptosis and immune responses through the TGR5 receptor. In this study, we reveal the interaction between TCDCA and TGR5 receptor in TGR5-knockdown H1299 cells and the regulation of inflammation via the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element binding (CREB) signal pathway in NR8383 macrophages. In TGR5-knockdown H1299 cells, TCDCA significantly activated cAMP level via TGR5 receptor, indicating TCDCA can bind to TGR5; in NR8383 macrophages TCDCA increased cAMP content compared to treatment with the adenylate cyclase (AC) inhibitor SQ22536. Moreover, activated cAMP can significantly enhance gene expression and protein levels of its downstream proteins PKA and CREB compared with groups of inhibitors. Additionally, TCDCA decreased tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-8 and IL-12 through nuclear factor kappa light chain enhancer of activated B cells (NF-κB) activity. PKA and CREB are primary regulators of anti-inflammatory and immune response. Our results thus demonstrate TCDCA plays an essential anti-inflammatory role via the signaling pathway of cAMP-PKA-CREB induced by TGR5 receptor.
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Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , AMP Cíclico/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/efectos de los fármacos , Ácido Tauroquenodesoxicólico/farmacología , Animales , Línea Celular , Citocinas/metabolismo , Humanos , Inflamación , Macrófagos , RatasRESUMEN
The incorporation of chemo/photothermal/photodynamic therapy in subcellular organelles such as mitochondria has attracted extensive attention recently. Here, we designed mitochondria-targeted hollow mesoporous silica nanoparticles (THMSNs) loaded biocompatible phase-change material L-menthol (LM) via a facile method. Meanwhile, antitumor drug doxorubicin (DOX) and near-infrared (NIR) dye indocyanine green (ICG) approved by FDA were simultaneously encapsulated into THMSNs, denoted as THMSNs@LMDI, which showed NIR radiation triggered capacity for cancer treatment. With the mitochondria-targeted ability of triphenylphosphine, the resulting THMSNs@LMDI showed evidently improved cellular internalization and specific accumulation in mitochondria. Under NIR irradiation, the versatile ICG would be bound to simultaneously produce photodynamic and photothermal therapy. Meanwhile, in view of the solid-liquid phase transition feature of gatekeeper LM, THMSNs@LMDI provided a platform for NIR-mediated temperature-responsive DOX release. As a matter of course, these smart subcellular organelle-THMSNs could serve as an effective drug delivery platform for site-specific on-demand chemo/photothermal/photodynamic therapy of cancer.
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Rayos Infrarrojos , Mitocondrias/metabolismo , Nanopartículas/química , Dióxido de Silicio/química , Materiales Biocompatibles/química , Materiales Biocompatibles/metabolismo , Materiales Biocompatibles/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Doxorrubicina/metabolismo , Doxorrubicina/farmacología , Portadores de Fármacos/química , Liberación de Fármacos , Humanos , Verde de Indocianina/química , Verde de Indocianina/metabolismo , Verde de Indocianina/farmacología , Mentol/química , Mentol/metabolismo , Mentol/farmacología , Mitocondrias/efectos de los fármacos , Nanopartículas/toxicidad , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Fotoquimioterapia , Fototerapia , Porosidad , Oxígeno Singlete/metabolismoRESUMEN
Safranal, a main component of Crocus sativus, is suggested to have neuroprotective effects. The aim of this study was to investigate the effect of safranal and nanostructured lipid vehicle (NLV) carried safranal in acute and chronic experimental mice models of epilepsy. In PILO acute seizure model, safranal dose-dependently extended latency to generalized seizure, decreased the highest seizure stages and the number of generalized seizures. Moreover, NLV carried safranal further enhanced the anti-seizure effect, which is comparable to the action of sodium valproate. Meanwhile, NLV carried safranal reduced and delayed the electroencephalogram spectra power after pilocarpine injection. In histological aspect, safranal dose-dependently reduced the loss of neurons induced by seizure and NLV system further improved this protection at the same dose. In MES acute model, safranal markedly increased the electroconvulsive threshold, where NLV further improved its effect. In PTZ chronic seizure model, NLV carried safranal significantly delayed the kindling rate of progress and the time it took to reach generalized seizures as compared to NLV control group. In conclusion, this study indicates that safranal inhibits generalized seizure in acute and chronic epilepsy models in mice and NLV can enhance this effect. So, NLV carried safranal may have potential value in treatment of generalized epilepsy.
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Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/uso terapéutico , Ciclohexenos/administración & dosificación , Ciclohexenos/uso terapéutico , Epilepsia Generalizada/tratamiento farmacológico , Terpenos/administración & dosificación , Terpenos/uso terapéutico , Animales , Convulsivantes , Relación Dosis-Respuesta a Droga , Composición de Medicamentos , Electroencefalografía , Electrochoque , Epilepsia Generalizada/inducido químicamente , Excitación Neurológica/efectos de los fármacos , Lípidos/química , Masculino , Ratones , Tamaño de la Partícula , Vehículos Farmacéuticos , PilocarpinaRESUMEN
BACKGROUND: Thalamic hemorrhage (TH) is a neurological insult with a high rate of morbidity and mortality. Moderate TH (10-30 ml) accounts for more than half of all TH. Treatment remains controversial. The role of acupuncture in patients with moderate TH is not clear. METHODS: We will conduct a single-center, randomized, parallel group, and assessor-blinded clinical trial. A total of 488 patients with moderate TH will be randomly assigned to one of eight groups: 10-15 cc left sided TH study group (N = 61) and a corresponding control group (N = 61), 10-15 cc right sided TH study group (N = 61) and a corresponding control group, 15-30 cc left sided TH study group (N = 61) and a corresponding control group (N = 61), and 15-30 cc right sided TH study group (N = 61) and a corresponding control group. Study groups will receive acupuncture in addition to standard treatment, while control groups will receive standard treatment alone. The primary outcome will be change in National Institutes of Health Stroke Scale scores at 30 and 90 days after TH. The secondary outcomes will be death or major disability, defined as a score of 3 to 6 on the modified Rankin scale (in which a score of 0 indicates no symptoms, a score of 5 indicates severe disability, and a score of 6 indicates death) at 90-days, need for surgery at 30-days, Glasgow Outcome Scale (GOS) score at 90-days following TH onset, and the results of several additional group specific tests. The rate of adverse events will then be compared between the groups. DISCUSSION: This study will attempt to answer the question of whether or not acupuncture can improve neurologic outcome following moderate TH. TRIAL REGISTRATION: Chinese clinical trial registry (ChiCTR-IOR-16008362).
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Terapia por Acupuntura , Hemorragias Intracraneales/terapia , Tálamo/patología , Puntos de Acupuntura , Enfermedad Aguda , Protocolos Clínicos , Femenino , Humanos , Masculino , Evaluación de Resultado en la Atención de Salud , Proyectos de Investigación , Accidente Cerebrovascular/terapiaRESUMEN
BACKGROUND: Shunt-dependent hydrocephalus (SDH) is a well-known sequela following aneurysmal hemorrhage, adversely affecting the outcome after securing ruptured aneurysm. Fenestration of lamina terminalis (FLT) creates an anterior ventriculostomy, facilitates cerebrospinal fluid circulation and clot clearance in the basal cistern. However, controversy exists over whether microsurgical FLT during aneurysm repair can decrease the incidence of SDH. AIMS: The study is designed to determine the efficacy of lamina terminalis fenestration on the reduction of SDH after aneurysm clipping. METHODS/DESIGN: A total of 288 patients who meet the inclusion criteria will be randomized into single aneurysm clipping or aneurysm clipping plus FLT in the Department of Neurosurgery, West China Hospital. Follow-up was performed 1, 3, 6, and 12 months after aneurysm clipping. The primary outcome is the incidence of SDH and the secondary outcomes include cerebral vasospasm, functional outcome evaluated by the modified Rankin Scale and Extended Glasgow Outcome Scale, and mortality. DISCUSSION: The FISH trial is a large randomized, parallel controlled clinical trial to define the therapeutic value of FLT, the results of which will help to guide the surgical procedure and resolve the long-puzzled debate in the neurosurgical community. CONCLUSIONS: This protocol will determine the efficacy of FLT in the setting of aneurysmal subarachnoid hemorrhage. TRIAL REGISTRATION IDENTIFIER: CHINESE CLINICAL TRIAL REGISTRY:: ChiCTR-INR-16009249.
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Hidrocefalia/prevención & control , Hipotálamo/cirugía , Hemorragia Subaracnoidea/cirugía , Ventriculostomía/métodos , Protocolos Clínicos , Humanos , Hidrocefalia/etiología , Hemorragia Subaracnoidea/complicacionesRESUMEN
BACKGROUND: Primary brainstem hemorrhage (BSH) has the highest mortality and morbidity as a subtype of intracerebral hemorrhage. A major limitation of BSH research is the lack of a corresponding animal model. The purpose of this study was to establish a novel rat model of BSH and to characterize the resulting brain injury, especially focusing on white matter injury. METHODS: BSH was produced by stereotactically injecting autologous whole blood into the pons. Time course of hematoma resolution was observed by 7-T magnetic resonance imaging. White matter injury was evaluated in detail by multiple parameters including diffuse tensor imaging (DTI), demyelination, axonal injury, oligodendrocyte degeneration, and oligodendrocyte precursor cell proliferation. Brain water content and neurobehavior were also evaluated. RESULTS: Blood infusion (30 µL) led to a stable, reproducible hematoma in the right basotegmental pons. The hematoma absorption started, became obvious, and was nearly completed at 7, 14, and 30 days, respectively. Hematoma caused obvious brain edema at 3 days. White mater injury was observed pathologically, which was in line with decreased fractional anisotropy (FA) in DTI in the pons. FA reduction was also noticed in the cerebral peduncle and medulla. Behavioral abnormality persisted for at least 14 days and neurofunction was recovered within 1 month. CONCLUSIONS: This novel model can produce a stable hematoma resulting in brain edema, white matter injury, and neurofunctional deficits, which could be useful for future investigation of pathophysiological mechanisms and new treatment evaluation after BSH.
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Conducta Animal , Transfusión de Sangre Autóloga , Edema Encefálico/etiología , Hematoma/etiología , Hemorragias Intracraneales/etiología , Leucoencefalopatías/etiología , Imagen por Resonancia Magnética , Puente/irrigación sanguínea , Sustancia Blanca/patología , Animales , Edema Encefálico/patología , Edema Encefálico/fisiopatología , Edema Encefálico/psicología , Imagen de Difusión Tensora , Modelos Animales de Enfermedad , Hematoma/patología , Hematoma/fisiopatología , Hematoma/psicología , Hemorragias Intracraneales/patología , Hemorragias Intracraneales/fisiopatología , Hemorragias Intracraneales/psicología , Leucoencefalopatías/patología , Leucoencefalopatías/fisiopatología , Leucoencefalopatías/psicología , Masculino , Puente/patología , Puente/fisiopatología , Ratas Sprague-Dawley , Factores de Tiempo , Sustancia Blanca/fisiopatologíaRESUMEN
The aim of this study was to investigate the effect of the tumortargeting recombinant human tumor necrosis factor (rhTNF)α fusion protein mediated by urokinase on Sl80 tumorbearing mice, as well as to explore its mechanisms of action. Furthermore, the study aimed to observe the effect of the protein on liver and kidney function. rhTNFα fusion protein prokaryotic expression vectors were constructed using genetic engineering techniques, and were introduced into Escherichia coli. Expression of the fusion protein was induced, and it was then separated and purified in order to determine its cytotoxic activity on L929 cells. Kunming mice were randomly divided into four groups after being inoculated with S180 tumor cells. The groups were then injected with saline (control group, group S), or saline with 0.1 µg/ml fusion protein (low dose group, group L), 0.2 µg/ml fusion protein (middle dose group, group M) or 0.3 µg/ml (high dose group, group H). The mice were sacrificed after 12 days and liver [mg/kg; (liver weight/body weight) x 1,000] and kidney [mg/kg; (kidney weight/body weight) x 1,000] indices, tumor weight, the percentage reduction in mean tumor size, and the levels of alanine transaminase (ALT), albumin (ALB), creatinine (Cr) and blood urea nitrogen (BUN) in each group of mice were determined. In addition, the levels of urokinasetype plasminogen activator (uPA), the expression of bcl2, bax and vascular endothelial growth factor (VEGF), and the percentage of apoptotic cells were measured with an enzymelinked immunosorbent assay, streptavidinbiotin complex of immunohistochemistry and terminal deoxynucleotidyl transferasemediated dUTP nick end labeling, respectively. The fusion protein significantly inhibited the growth of S180 tumor cells in vivo in a dosedependent manner. With an increase in the dose of fusion protein, ALT, uPA, bcl2 and VEGF levels decreased, and ALB levels increased. However, liver and kidney indices and bax expression were not significantly altered. Cr and BUN levels did not change significantly in the low and middle dose groups, but did increase in the high dose group. Compared with the control group, the percentage of apoptotic cells in the highdose group was significantly higher. In conclusion, the fusion protein significantly inhibited S180 tumor growth in a mouse model, possibly by reducing the levels of uPA, bcl2 and VEGF. There was a mildly toxic effect on the kidneys with the high dose, but a protective effect in the liver.
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Antineoplásicos/farmacología , Proteínas Recombinantes de Fusión/farmacología , Factor de Necrosis Tumoral alfa/farmacología , Activador de Plasminógeno de Tipo Uroquinasa/metabolismo , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Mutación , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteínas Recombinantes de Fusión/genética , Carga Tumoral/efectos de los fármacos , Factor de Necrosis Tumoral alfa/genética , Activador de Plasminógeno de Tipo Uroquinasa/sangre , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteína X Asociada a bcl-2/genética , Proteína X Asociada a bcl-2/metabolismoRESUMEN
The ratio between FABP5 and CRABPII determines cellular response to physiological level of retinoic acid; tumor cells undergo proliferation with high level of FABP5 and apoptosis with high level of CRABPII. We intended to study FABP5 and CRABPII expression in craniopharyngiomas, to establish craniopharyngioma cell model using explants method, and to study the effect of pharmacological dose of retinoic acid on craniopharyngioma cells. Expression of FABP5 and CRABPII in craniopharyngioma tissue from 20 patients was studied using immunohistochemistry. Primary craniopharyngioma cell cultures were established using tissue explants method. Craniopharyngioma cells were treated using various concentrations of all-trans retinoic acid, and cell growth curve, apoptosis, expression of FABP5, CRABPII and NF-κB were assayed in different groups. FABP5/CRABPII ratio was significantly higher in adamatinomatous group than that in papillary group. Cell cultures were established in 19 cases (95 %). Pharmacological level retinoic acid inhibited cell growth and induced cellular apoptosis in dose dependent manner, and apoptosis rate cells treated with 30 µM retinoic acid for 24 h was 43 %. Also, retinoic acid increased CRABPII, and decreased FABP5 and NF-κB expression in craniopharyngioma cells. High FABP5/CRABPII ratio is observed in adamatinomatous craniopharyngioma. Retinoic acid at pharmacological level induced craniopharyngioma cell apoptosis via increasing FABP5/CRABPII ratio and inhibiting NF-κB signaling pathway. Our study demonstrated that all-trans retinoic acid might be a candidate for craniopharyngioma adjuvant chemotherapy in future.
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Antineoplásicos/farmacología , Proliferación Celular/efectos de los fármacos , Craneofaringioma/metabolismo , Neoplasias Hipofisarias/metabolismo , Tretinoina/farmacología , Adolescente , Adulto , Apoptosis/efectos de los fármacos , Western Blotting , Células Cultivadas , Niño , Preescolar , Proteínas de Unión a Ácidos Grasos/biosíntesis , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Receptores de Ácido Retinoico/biosíntesis , Adulto JovenRESUMEN
Calcium is an essential element and imparts significant structural rigidity to the plant cell walls, which provide the main mechanical support to the entire plant. In order to increase the mechanical strength of the inflorescence stems of herbaceous peony, the stems are treated with calcium chloride. The results shows that preharvest sprays with 4% (w/v) calcium chloride three times after bud emergence are the best at strengthening "Da Fugui" peonies' stems. Calcium sprays increased the concentrations of endogenous calcium, total pectin content as well as cell wall fractions in herbaceous peonies stems, and significantly increased the contents of them in the top segment. Correlation analysis showed that the breaking force of the top segment of peonies' stems was positively correlated with the ratio of water insoluble pectin to water soluble pectin (R = 0.673) as well as lignin contents (R = 0.926) after calcium applications.
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Cloruro de Calcio/administración & dosificación , Pared Celular/fisiología , Inflorescencia/fisiología , Tallos de la Planta/fisiología , Resistencia a la Tracción/efectos de los fármacos , Cloruro de Calcio/química , Pared Celular/química , Celulosa/metabolismo , Inflorescencia/citología , Lignina/metabolismo , Paeonia , Pectinas/química , Tallos de la Planta/citología , Ácidos Urónicos/metabolismoRESUMEN
This study was designed to investigate the effect of pulse width modulation electro-acupuncture (PWM-EA) on cardiovascular remodeling and nitric oxide (NO) in spontaneously hypertensive rats (SHR). Thirty-four male SHR were randomly divided into control, captopril, and two PWM-EA groups, which were treated with 350 Hz (SHR-350 Hz) and whole audio bandwith electro-acupuncture (SHR-WAB group) respectively, on the ST 36 point located on the outside of the hind leg. Systolic blood pressure (BP), plasma and myocardial NO were measured. Histological studies were also performed on the aortic wall and the left ventricle. The BP in the SHR-350 Hz, SHR-WAB and the captopril groups was lower than in the control group following the treatment (P < .05). The average aortic media wall thickness in the two electro-acupuncture groups was less than in the control group (P < .05). The left ventricle/heart weight ratio in the captopril and SHR-350 Hz groups was less than in the control group (P < .01), but was similar between the SHR-WAB and the control group (P > .05). The plasma and myocardium NO levels were elevated in the captopril and the SHR-350 Hz group (P < .05 and .01, resp.). The plasma level of NO in the SHR-WAB group was also higher than in the control group (P < .05). We concluded that pulse width modulation electro-acupuncture on the ST 36 point prevents the progression of hypertension and diminishes the cardiovascular remodeling in SHR. It also elevates plasma and cardiac NO in this animal model.
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The effects of electro-acupuncture (EA) on insulin-like growth factor-I (IGF-I) expression in the spared dorsal root ganglia (DRG) and associated spinal dorsal horns were explored in cats subjected to unilateral removal of L(1)-L(5) and L(7)-S(2) DRG, sparing the L(6) DRG. Immunohistochemistry revealed the presence of IGF-I immunoreactive products in the L(6) DRG neurons and some neurons and glial cells in the spinal cord. Western blot demonstrated that the level of IGF-I was significantly up-regulated both in the spared DRG and the dorsal horns of L(3) and L(6) cord segments at both 7 and 14 days post operation following EA. The present findings demonstrated the association between neuroplasticity and IGF-I expression, suggesting the possible role of IGF-I in EA promoted spinal cord plasticity.
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Electroacupuntura , Ganglios Espinales/metabolismo , Factor I del Crecimiento Similar a la Insulina/biosíntesis , Células del Asta Posterior/metabolismo , Animales , Gatos , Ganglionectomía , Inmunohistoquímica , Masculino , Neuroglía/metabolismo , Plasticidad NeuronalRESUMEN
OBJECTIVE: To explore the effects of hyperbaric oxygen (HBO) treatment on the neuronal apoptosis at an earlier stage and the expressions of Cytochrome C (Cyt C), Bcl-2 (B-cell lymphoma-2 family) and Bax (Bcl-2 associated X protein) in rat brain tissues after traumatic brain injury (TBI). METHODS: Forty adult rats were divided into two groups, i.e., Group A (the rats with untreated TBI) and Group B (rats with HBO treatment after TBI). Sections of brain tissues of these two groups were then detected at 3, 6, 12, 24, 72 hours after TBI by immunohistochemistry and electronmicroscope, respectively. RESULTS: HBO treatment could up-regulate the expression of Bcl-2 within 72 hours, reduce the release of Cyt C from mitochondria, attenuate the formation of dimeric Bax and alleviate the mitochondrial edema within 24 hours after TBI. CONCLUSIONS: HBO treatment can alleviate neuronal apoptosis after TBI by reducing the release of Cyt C and the dimers of Bax and up-regulating the expression of Bcl-2.
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Lesiones Encefálicas/terapia , Citocromos c/biosíntesis , Oxigenoterapia Hiperbárica , Proteínas Proto-Oncogénicas c-bcl-2/biosíntesis , Proteína X Asociada a bcl-2/biosíntesis , Análisis de Varianza , Animales , Apoptosis/fisiología , Lesiones Encefálicas/patología , Modelos Animales de Enfermedad , Inmunohistoquímica , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To study the biological features and osteoblast/adipocyte phenotypes of bone marrow stromal cells (BMSCs) of Sprague-Dawley (SD) rats with Type I osteoporosis by induced culture. METHODS: Six-month-old SD rats were used in this study. 16 female rats were randomly divided into two groups. Eight rats were ovariectomied as experimental group to establish the modle of Type I osteoporosis, while other rats received sham-operation. Three month later BMSCs of 16 rats were isolated by discontinueous gradient centrifugation and then plated in alpha-MEM medium as primary culture. Secondary harvested cells were cultured for 14 days in alpha-MEM medium supplemented with dexamethasone, ascorbic acid, vitamin D3, beta-glycerophosphate or dexamethasone, 3-isobutyl-1-methylxanthine, insuline, and indomethine. The cells were screened by inverted microscope each day and cell growth was studied with cell counting. The osteoblast and adipocyte phenotypes were verified by cytochemistry staining, counted the percentage of positive stained cells. RESULTS: The weight and bone mineral density of rats were statistically different between experimental group and control group. Gomori and Von Kossa's staining demonstrated positive osteoblast phenotypes of alkaline phosphatase and mineralized nods by osteogenic inducer, while Oil Red O staining identified BMSCs treated with adipogenic medium resulted in adipocyte formation and there was no significant difference in the percentage of positive stained cells between two groups. CONCLUSION: The model of Type I osteoporosis has been established successfully. BMSCs from SD rats with osteoporosis maintain their differentiation potential.
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Diferenciación Celular , Células Madre Mesenquimatosas , Osteoporosis/fisiopatología , Adipocitos , Animales , Densidad Ósea , Células de la Médula Ósea , Proliferación Celular , Células Cultivadas , Femenino , Osteoblastos , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To investigate the effects of Extract of Ginkgo biloba on ICAM-1 and mRNA expression in rats with cerebral injury, and discuss its protective mechanism. METHODS: The acute closed brain injury model was set up in rats according Feeney's method. Seventy-two rats were randomly divided into four groups. The levels of ICAM-1 expression were observed using immunohistochemistry and computerized imaging technique and the expression of mRNA were studied using RT-PCR techniques. RESULTS: ICAM-1 positive cells located in the transitional zone between the necrotic core and normal cortex. ICAM-1 protein and mRNA expression began to show 6 hours after cerebral injury, peaked at 24 hours. As compared with the model group, ICAM-1 and mRNA expression was significantly reduced in the group EGb (P < 0.01). CONCLUSION: EGb can markedly reduce the injury of nerve cell in the transitional zone, alleviate rat cerebral injury, and decrease ICAM-1 and mRNA expression and neutrophils infiltration. The protection may be related with its inhibition on ICAM-1 and mRNA expression.
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Lesiones Encefálicas/metabolismo , Ginkgo biloba/química , Molécula 1 de Adhesión Intercelular/biosíntesis , Fármacos Neuroprotectores/farmacología , Plantas Medicinales/química , Animales , Encéfalo/metabolismo , Femenino , Molécula 1 de Adhesión Intercelular/genética , Hojas de la Planta/química , ARN Mensajero/biosíntesis , Ratas , Ratas Sprague-DawleyRESUMEN
<p><b>OBJECTIVE</b>To study the biological features and osteoblast/adipocyte phenotypes of bone marrow stromal cells (BMSCs) of Sprague-Dawley (SD) rats with Type I osteoporosis by induced culture.</p><p><b>METHODS</b>Six-month-old SD rats were used in this study. 16 female rats were randomly divided into two groups. Eight rats were ovariectomied as experimental group to establish the modle of Type I osteoporosis, while other rats received sham-operation. Three month later BMSCs of 16 rats were isolated by discontinueous gradient centrifugation and then plated in alpha-MEM medium as primary culture. Secondary harvested cells were cultured for 14 days in alpha-MEM medium supplemented with dexamethasone, ascorbic acid, vitamin D3, beta-glycerophosphate or dexamethasone, 3-isobutyl-1-methylxanthine, insuline, and indomethine. The cells were screened by inverted microscope each day and cell growth was studied with cell counting. The osteoblast and adipocyte phenotypes were verified by cytochemistry staining, counted the percentage of positive stained cells.</p><p><b>RESULTS</b>The weight and bone mineral density of rats were statistically different between experimental group and control group. Gomori and Von Kossa's staining demonstrated positive osteoblast phenotypes of alkaline phosphatase and mineralized nods by osteogenic inducer, while Oil Red O staining identified BMSCs treated with adipogenic medium resulted in adipocyte formation and there was no significant difference in the percentage of positive stained cells between two groups.</p><p><b>CONCLUSION</b>The model of Type I osteoporosis has been established successfully. BMSCs from SD rats with osteoporosis maintain their differentiation potential.</p>
Asunto(s)
Animales , Femenino , Ratas , Adipocitos , Densidad Ósea , Células de la Médula Ósea , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Células Madre Mesenquimatosas , Osteoblastos , Osteoporosis , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To investigate the effect of compound Salvia injection (CSI) on blood coagulatory function in patients with traumatic cerebral infarction (TCI). METHODS: Sixty-four patients with TCI were randomly divided into two groups, 32 in each group. The treated group were treated with CSI plus conventional treatment of western medicine, and the control group treated with conventional treatment alone. Changes of symptoms, levels of plasma P-selectin (P-S), von Willebrand's factor (vWf) and D-dimer were observed with ELISA. RESULTS: The treated group was superior to the control group in Glasgow outcome scale (P < 0.01). Before treatment, the levels of plasma P-S, vWf and D-dimer in the TCI patients were higher than those in healthy people. After treatment, all the parameters lowered in both groups, but the effect of lowering was greater in the treated group than that in the control group. CONCLUSION: Blood coagulation disorder exists in patients with TCI, CSI could improve it, and might alleviate the cerebral damage to a certain extent.