RESUMEN
Sleep deprivation,the process and state of partial or complete lack of normal sleep caused by various factors,is prevalent at present.Seriously impairing the physical and mental health,sleep deprivation has become a public health problem that cannot be ignored.Studies have demonstrated that blood-brain barrier impairment is the key pathophysiological process of a variety of neurological diseases.Although clinical and basic studies have suggested that sleep deprivation can induce blood-brain barrier impairment,the underlying mechanisms remain to be elucidated.This review summarizes the advances in the mechanisms of blood-brain barrier impairment induced by sleep deprivation.
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Barrera Hematoencefálica , Privación de Sueño , Humanos , Privación de Sueño/complicaciones , EncéfaloRESUMEN
Anxiety and depression induced by cancer-related pain disturb quality of life and willingness to survive. As a component of the limbic system, the basolateral amygdala (BLA) is critical for processing negative emotions. The reactive microglial engulfment of synapses may promote depression during adolescence. However, whether microglia phagocytose synapses to mediate cancer pain-induced depression remains unclear. The present study established a bone cancer-pain model to investigate the association between dendritic spine synapses and depressive-like behavior and explore the phagocytic function of microglia in the BLA. We found that tumor-bearing mice experienced postoperative pain-related depression, and their BLAs exhibited reactive microglia, as well as phagocytic synapses. The microglial inhibitor minocycline effectively mitigated depressive behavior, synaptic damage, and the phagocytic function of microglia. Our study implicates microglia-mediated synaptic loss in the BLA may act as the pathological basis of depressive-like behavior in bone cancer pain model.
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Complejo Nuclear Basolateral , Neoplasias Óseas , Dolor en Cáncer , Animales , Neoplasias Óseas/complicaciones , Ratones , Microglía , Minociclina/farmacología , Calidad de VidaRESUMEN
To investigate the inhibitory effects of chlorogenic acid on pulmonary fibrosis and the internal mechanisms in vivo and in vitro. 30 male BALB/C mice were randomized into 5 groups: control group, pulmonary fibrosis model group, low, middle and high dose of chlorogenic acid groups. Mice in pulmonary fibrosis model group were administered 5.0 mg/kg bleomycin with intracheal instillation and mice in 3 chlorogenic acid groups were treated with chlorogenic acid every day for 28 days after bleomycin administration. Lung tissue histology was observed using HE staining. Primary pulmonary fibroblasts were isolated and cultured. The expressions of fibrosis related factors (α-SMA and collagen I), as well as ER stress markers (CHOP and GRP78) were determined by both real-time PCR assay and Western blotting, while the expressions of other ER stress signaling pathway factors PERK, IRE-1, ATF-6 and protein levels of caspase-12, caspase-9, caspase-3, PARP were determined by Western blotting. RLE-6TN cell line induced by TGF-ß1 was also used to verify the amelioration effects in vitro study. In both in vivo and in vitro studies, TUNEL staining was used to evaluate cell apoptosis. Expressions of collagen I, α-SMA, GRP78, and CHOP were significantly inhibited by chlorogenic acid in dose-dependent manner. Similarly, decreasing levels of cleaved caspase-12, caspase-9, caspase-3 and increasing level of uncleaved PARP were observed in chlorogenic acid groups compared with those in the fibrosis group both in vivo and in vitro. Chlorogenic acid could also significantly down-regulate the level of phosphorylation of PERK and cleaved ATF-6 in vivo study. Moreover, MTT assay demonstrated chlorogenic acid could enhance proliferation of RLE-6TN cells induced by TGFß1 in vitro. And the apoptosis assays indicated that chlorogenic acid could significantly inhibit cell apoptosis both in vivo and in vitro studies. Chlorogenic acid could inhibit the pulmonary fibrosis through endoplasmic reticulum stress inhibition in vivo and in vitro.
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Bleomicina , Ácido Clorogénico/farmacología , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico/efectos de los fármacos , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Animales , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Células Cultivadas , Chaperón BiP del Retículo Endoplásmico , Fibroblastos/metabolismo , Fibroblastos/patología , Fibroblastos/fisiología , Masculino , Ratones , Ratones Endogámicos BALB C , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/fisiopatología , Transducción de Señal/efectos de los fármacos , Factor de Crecimiento Transformador beta1/farmacologíaRESUMEN
OBJECTIVE: To assess the clinical applicability of focused transthoracic echocardiography (TTE) in intensive care unit (ICU) performed by intensivists and its impacts on clinical managements. METHODS: After 12-hour tutorials and initial cardiac clinical assessments, intensivists performed a focused TTE (2-4 views of 2D, without Doppler or M mode) examination in 88 patients to assess left ventricular function and left ventricular volume status, and rule out local ventricular wall motion abnormalities and significant pericardial effusions. Each investigation was immediately reviewed by an echocardiograph to determine the technical quality of the TTE and the accuracy of the intensivist's interpretation. RESULTS: Intensivists successfully performed a diagnostic focused TTE in 86 patients (97.7%) and interpreted correctly in 75 patients (85.2%). Management including fluid treatment, inotropic agent and vasoactive agent in 22.7% of patients were changed directly based on the focused TTE, 45.5% of patients were provided with valuable information, while 31.8% of them with non-valuable information. The mean focused TTE acquisition time of the intensivist was (11.2±5.2) minutes. CONCLUSIONS: After a brief standard training in using echocardiographic system, intensivists can successfully performed and correctly interpreted a focused TTE for critically ill patients. Our study demonstrates that new information can be provided by focused TTE, which can alter management in a significant number of patients. The present study supports incorporating bedside goal-directed, focused TTE into intensivists' training programs in China.
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Ecocardiografía , Unidades de Cuidados Intensivos , Sistemas de Atención de Punto , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crítica , Ecocardiografía Doppler , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Médicos , Estudios ProspectivosRESUMEN
Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury.