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BACKGROUND: Hypothermia is a promising therapy for traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI patients in clinical studies are inconsistent due to several severe side effects. Here, an injectable refrigerated hydrogel was designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. Hydrogel has four advantages: (1) It can be injected into injured sites after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling. (2) Hydrogels can biodegrade and be used for controlled drug release. (3) Released T1AM can induce hypothermia. (4) This hydrogel has increased medical value given its simple operation and ability to achieve timely treatment. METHODS: Pol/T hydrogels were prepared by a low-temperature mixing method and characterized. The effect of the Pol/T hydrogel on traumatic brain injury in mice was studied. The degradation of the hydrogel at the body level was observed with a small animal imager. Brain temperature and body temperature were measured by brain thermometer and body thermometer, respectively. The apoptosis of peripheral nerve cells was detected by immunohistochemical staining. The protective effect of the hydrogels on the blood-brain barrier (BBB) after TBI was evaluated by the Evans blue penetration test. The protective effect of hydrogel on brain edema after injury in mice was detected by Magnetic resonance (MR) in small animals. The enzyme linked immunosorbent assay (ELISA) method was used to measure the levels of inflammatory factors. The effects of behavioral tests on the learning ability and exercise ability of mice after injury were evaluated. RESULTS: This hydrogel was able to cool the brain to hypothermia for 12 h while maintaining body temperature within the normal range after TBI in mice. More importantly, hypothermia induced by this hydrogel leads to the maintenance of BBB integrity, the prevention of cell death, the reduction of the inflammatory response and brain edema, and the promotion of functional recovery after TBI in mice. This cooling method could be developed as a new approach for hypothermia treatment in TBI patients. CONCLUSION: Our study showed that injectable and biodegradable frozen Pol/T hydrogels to induce local hypothermia in TBI mice can be used for the treatment of traumatic brain injury.
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Barrera Hematoencefálica , Lesiones Traumáticas del Encéfalo , Hidrogeles , Hipotermia Inducida , Animales , Lesiones Traumáticas del Encéfalo/terapia , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Ratones , Hidrogeles/química , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de los fármacos , Masculino , Hipotermia Inducida/métodos , Neuroprotección/efectos de los fármacos , Encéfalo/patología , Modelos Animales de Enfermedad , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/química , Temperatura Corporal , Ratones Endogámicos C57BLRESUMEN
AIM: To investigate the trajectory patterns and influencing factors of supportive care needs in stroke patients. DESIGN: A longitudinal study. METHODS: In total, 207 stroke patients who received treatment at the Department of Neurology in a hospital in Xuzhou between July 2022 and July 2023 were recruited using convenience sampling. Questionnaires including supportive care needs, hospital anxiety and depression scale, and the Barthel index were investigated at baseline and at 1, 3, and 6 months. A latent class growth model was applied to identify the supportive care needs trajectories. Multiple logistic regression was used to determine the predictors for membership. This study adheres to STROBE reporting guidelines. RESULTS: Three patterns of supportive care needs trajectories were identified: A high needs slow decline group (20.8%), a medium needs stable group (56.5%) and a medium needs rapid decline group (22.7%). Based on further analysis, the findings indicated that age, education level, monthly income, comorbidity, activities of daily living, anxiety and depression were associated with the trajectory categories of supportive care needs with stroke patients. CONCLUSION: This study demonstrates heterogeneity in changes in supportive care needs among stroke patients. Healthcare providers need to consider these different categories of needs and develop individualized care measures based on the characteristics of different patients. IMPACT: Healthcare providers should be aware of the fluctuations in care needs of stroke patients at various stages. Additionally, the study aimed to identify patients' specific needs based on their circumstances, monitor the rehabilitation process and establish a more personalized and optimized care plan through multidisciplinary collaboration. The ultimate goal was to alleviate symptomatic distress and address the long-term care needs of patients. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.
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OBJECTIVE: Toll-like receptor-2 (TLR2), a member of TLR family, plays an important role in the induction and regulation of immune/inflammation. TLR2 gene knockout (TLR2KO) mice have been widely used for animal models of neurological diseases. Since there is close relationship between immune system and neurobehavioral functions, it is important to clarify the exact role of TLR2 defect itself in neurobehavioral functions. The present study aimed to investigate the effect of TLR2KO on neurobehavioral functions in mice and the mechanisms underlying the observed changes. METHODS: Male TLR2KO and wild type (WT) mice aged 3, 7, and 12 months were used for neurobehavioral testing and detection of protein expression by Western blot. Brain magnetic resonance imaging (MRI), electrophysiological recording, and Evans blue (EB) assay were applied to evaluate regional cerebral blood flow (rCBF), synaptic function, and blood-brain barrier (BBB) integrity in 12-month-old TLR2KO and age-matched WT mice. RESULTS: Compared to WT mice, TLR2KO mice showed decreased cognitive function and locomotor activity, as well as increased anxiety, which developed from middle age (before 7-month-old) to old age. In addition, significantly reduced regional cerebral blood flow (rCBF), inhibited long-term potentiation (LTP), and increased blood-brain barrier (BBB) permeability were observed in 12-month-old TLR2KO mice. Furthermore, compared with age-matched WT mice, significant reduction in protein levels of tight junction proteins (ZO-1, Occludin, and Claudin-5) and increased neurofilament protein (SMI32) were observed in 7 and 12-month-old TLR2KO mice, and that myelin basic protein (MBP) decreased in 12-month-old TLR2KO mice. CONCLUSION: Our data demonstrated that TLR2 defect resulted in significantly observable neurobehavioral dysfunctions in mice starting from middle age, as well as multiple abnormalities in brain structure, function, and molecular metabolism.
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Barrera Hematoencefálica , Encéfalo , Animales , Técnicas de Inactivación de Genes , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
OBJECTIVES: To determine the average modern adult cranial capacity in China, and assess the gender differences and trends in order to establish normal reference values and provide theoretical basis for individualized treatment in clinical practice. METHODS: We conducted a cross-sectional study between January 2019 to June 2020. Thin-slice (0.9 mm) CT scans of 309 males and 238 females from China were obtained, and classified into the 18-32, 33-47, 48-62, 63-77 and 78-92 years age groups. Three-dimensional reconstruction was performed using mimics software to obtain the cranial capacity for statistical analysis. RESULTS: The average cranial capacity of men was 1497.12±120.70 cm3 and that of women was 1326.24±95.72 cm3. The average cranial capacity of men was larger than that of women in all age groups. In addition, cranial capacity across the different age groups showed significant differences among both men and women. CONCLUSION: The average cranial capacity of modern Chinese male is larger that of females, and both sexes show a tendency to an increase in the intracranial volume over the past few decades. Our findings provide important data for establishing normal reference values for cranial capacity of modern Chinese adults and theoretical basis for individualized treatment of certain cranial diseases with increased intracranial pressure.
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Imagenología Tridimensional , Tomografía Computarizada por Rayos X , Adulto , China , Estudios Transversales , Femenino , Humanos , Masculino , Factores SexualesRESUMEN
INTRODUCTION: Data on the associations between esophageal histological lesions and risk of esophageal squamous cell carcinoma (ESCC) in general populations are limited. We aimed to investigate these associations in a large Chinese general population to inform future Chinese ESCC screening guidelines. METHODS: We performed endoscopic screening of 21,111 participants aged 40-69 years from 3 high-risk areas of China in 2005-2009, and followed the cohort through 2016. Cumulative incidence and mortality rates of ESCC were calculated by baseline histological diagnosis, and hazard ratios of ESCC, overall and by age and sex, were assessed using the Cox proportional hazards models. RESULTS: We identified 143 new ESCC cases (0.68%) and 62 ESCC deaths (0.29%) during a median follow-up of 8.5 years. Increasing grades of squamous dysplasia were associated with the increasing risk of ESCC incidence and mortality. The cumulative ESCC incidence rates for severe dysplasia/carcinoma in situ, moderate dysplasia (MD), and mild dysplasia were 15.5%, 4.5%, and 1.4%, respectively. Older individuals (50-69 years) had 3.1 times higher ESCC incidence than younger individuals (40-49 years), and men had 2.4 times higher ESCC incidence than women. DISCUSSION: This study confirmed that increasing grades of squamous dysplasia are associated with increasing risk of ESCC and that severe dysplasia and carcinoma in situ require clinical treatment. This study suggests that in high-risk areas of China, patients with endoscopically worrisome MD should also receive therapy, the first screening can be postponed to 50 years, and endoscopic surveillance intervals for unremarkable MD and mild dysplasia can be lengthened to 3 and 5 years, respectively.
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Neoplasias Esofágicas/epidemiología , Neoplasias Esofágicas/patología , Lesiones Precancerosas/epidemiología , Lesiones Precancerosas/patología , Adulto , Anciano , Biopsia , China/epidemiología , Esofagoscopía , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Riesgo , Encuestas y CuestionariosRESUMEN
The objective of the study was to examine the correlations between intracranial aneurysm morphology and wall shear stress (WSS) to identify reliable predictors of rupture risk. Seventy-two intracranial aneurysms (41 ruptured and 31 unruptured) from 63 patients were studied retrospectively. All aneurysms were divided into two categories: narrow (aspect ratio ≥1.4) and wide-necked (aspect ratio <1.4 or neck width ≥4 mm). Computational fluid dynamics was used to determine the distribution of WSS, which was analyzed between different morphological groups and between ruptured and unruptured aneurysms. Sections of the walls of clipped aneurysms were stained with hematoxylin-eosin, observed under a microscope, and photographed. Ruptured aneurysms were statistically more likely to have a greater low WSS area ratio (LSAR) (P = 0.001) and higher aneurysms parent WSS ratio (P = 0.026) than unruptured aneurysms. Narrow-necked aneurysms were statistically more likely to have a larger LSAR (P < 0.001) and lower values of MWSS (P < 0.001), mean aneurysm-parent WSS ratio (P < 0.001), HWSS (P = 0.012), and the highest aneurysm-parent WSS ratio (P < 0.001) than wide-necked aneurysms. The aneurysm wall showed two different pathological changes associated with high or low WSS in wide-necked aneurysms. Aneurysm morphology could affect the distribution and magnitude of WSS on the basis of differences in blood flow. Both high and low WSS could contribute to focal wall damage and rupture through different mechanisms associated with each morphological type.
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Aneurisma Roto , Hemodinámica , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Aneurisma Roto/diagnóstico por imagen , Aneurisma Roto/patología , Aneurisma Roto/fisiopatología , Aneurisma Roto/cirugía , Angiografía Cerebral , Circulación Cerebrovascular , Femenino , Humanos , Imagenología Tridimensional , Aneurisma Intracraneal/patología , Aneurisma Intracraneal/cirugía , Masculino , Persona de Mediana Edad , Modelos Cardiovasculares , Modelos Neurológicos , Estudios Retrospectivos , Riesgo , Tomografía Computarizada por Rayos X , Ultrasonografía Doppler TranscranealRESUMEN
OBJECTIVE: To measure morphological indices and wall shear stress (WSS) of aneurysms and parent artery surface in order to explore the relationship of morphological characteristics and WSS. METHODS: Data from 47 events of consecutive cerebral saccular aneurysms from 39 patients which were referred to the interventional Neuroradiology service of the Shaoxing People`s Hospital, Shaoxing, China between 2014 April and 2015 August. Wall shear stress and wall pressure (WP) of the pre-aneurysm, aneurysm and near vessel (<1.0 cm) surface were obtained. Correlation analysis was carried between morphological parameters and WSS and its ratio. WSS, WP, intra-aneurysmal flow pattern, and location of aneurysms were analyzed. RESULTS: Impaction zone from inflow jet was located in the distal neck part of aneurysm with high WSS in 36 aneurysms (76.6%). There were significant differences in WSS between pre-aneurysm surface and near vessel (p<0.001), aneurysm (p<0.001), aneurysm and near vessel (p<0.001). Significant correlations were found between aneurysm WSS and aspect ratio (r=-0.296), aneurysm-artery WSS ratio and size ratio (r=-0.322), aspect ratio (r=-0.416). CONCLUSION: Uneven WSS distributes in the various part of the pre-aneurysm vessel. The impaction zone from inflow jet is located in the distal neck of aneurysm. Aspect and size ratios can effect aneurysm WSS.
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Encéfalo/irrigación sanguínea , Hemodinámica/fisiología , Hidrodinámica , Aneurisma Intracraneal/fisiopatología , Estrés Mecánico , Angiografía Cerebral/métodos , Humanos , Imagenología TridimensionalRESUMEN
OBJECTIVE: To investigate the correlations between morphological parameters and rupture status in cerebral aneurysm patients. METHODS: We conducted a retrospective study of 34 patient records from March 2010 to December 2012. The morphological parameters of 34 ruptured and 42 unruptured cerebral aneurysms in 34 patients (males: female, 15:19; mean age 55.79+/-10.64 years) leading to subarachnoid hemorrhage were examined using 3D (dimension) digital subtraction angiography (DSA) models, to identify the correlation between 2D morphological parameters and risk factors of rupture status with univariate and multivariate analysis. RESULTS: The 2D morphological parameters in ruptured aneurysms were significantly different from those observed in unruptured aneurysms (p<0.05), though only size and height-width ratios independently predicted rupture status. Dmax, Hmax, bottleneck factor, and size ratio significantly correlated with height-width ratio in ruptured but not unruptured aneurysms. CONCLUSION: A specific set of morphological characteristics, most notably size and height-width ratios, may help to understand rupture risk by indicating arterial stretch character in cerebral aneurysms patients.
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Aneurisma Roto/diagnóstico por imagen , Angiografía de Substracción Digital/métodos , Aneurisma Intracraneal/diagnóstico por imagen , Hemorragia Subaracnoidea/diagnóstico por imagen , Adulto , Anciano , Femenino , Humanos , Imagenología Tridimensional/métodos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Prior to gastrulation, the Wnt signaling pathway through stabilized ß-catenin enhances the differentiation of mouse ES cell into cardiomyocytes. We have recently shown that cardiomyocyte differentiation is enhanced by eosinophil cationic protein (ECP) through accelerated expression of marker genes of early cardiac differentiation. Furthermore, ECP enhanced the expression of Wnt3a in P19CL6 cells which were stimulated to differentiate into cardiomyocytes by DMSO. Following these findings, we evaluated in this study the potential of ECP to activate the Wnt/ß-catenin signaling pathway during cardiomyocyte differentiation. Analysis by real time qPCR revealed that ECP increased the expression of Frizzled genes such as Frizzled-1, -2, -4 and -10 in P19CL6 cells in the presence of DMSO. The increased expression of those Wnt receptors was found to inhibit the phosphorylation of ß-catenin resulting in the stabilization and translocation of ß-catenin into the nucleus of P19CL6 cells during the early stages of cardiomyocyte differentiation. When assessed for ß-catenin/TCF transcriptional activity with a TCF-luciferase (TOP/FOP) assay, ECP enhanced luciferase activity in P19CL6 cells during 48 h after transfection with TOP/FOP flash reporter in a stoichiometric manner. Collectively, this suggests that ECP can activate a canonical Wnt/ß-catenin signaling pathway by enhancing the stabilization of ß-catenin during cardiomyocyte differentiation.
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Diferenciación Celular/genética , Proteína Catiónica del Eosinófilo/genética , Vía de Señalización Wnt , beta Catenina/metabolismo , Animales , Células Madre de Carcinoma Embrionario , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Regulación del Desarrollo de la Expresión Génica , Humanos , Ratones , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , beta Catenina/genéticaRESUMEN
OBJECTIVE: Progesterone receptor membrane component 2 (PGRMC2) belongs to the membrane-associated progesterone receptor family, which regulates multiple pathophysiological processes. However, the role of PGRMC2 in ischemic stroke remains unexplored. The present study sought to determine the regulatory role of PGRMC2 in ischemic stroke. METHODS: Male C57BL/6J mice were subjected to middle cerebral artery occlusion (MCAO). The protein expression level and localization of PGRMC2 were examined by western blotting and immunofluorescence staining. The gain-of-function ligand of PGRMC2 (CPAG-1, 45 mg/kg) was intraperitoneally injected into sham/MCAO mice, and brain infarction, blood-brain barrier (BBB) leakage, and sensorimotor functions were evaluated by magnetic resonance imaging, brain water content, Evans blue extravasation, immunofluorescence staining, and neurobehavioral tests. The astrocyte and microglial activation, neuronal functions, and gene expression profiles were revealed by RNA sequencing, qPCR, western blotting, and immunofluorescence staining after surgery and CPAG-1 treatment. RESULTS: Progesterone receptor membrane component 2 was elevated in different brain cells after ischemic stroke. Intraperitoneal delivery of CPAG-1 reduced infarct size, brain edema, BBB leakage, astrocyte and microglial activation, and neuronal death, and improved sensorimotor deficits after ischemic stroke. CONCLUSION: CPAG-1 acts as a novel neuroprotective compound that could reduce neuropathologic damage and improve functional recovery after ischemic stroke.
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Lesiones Encefálicas , Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Masculino , Ratones , Barrera Hematoencefálica/metabolismo , Lesiones Encefálicas/patología , Isquemia Encefálica/metabolismo , Mutación con Ganancia de Función , Infarto de la Arteria Cerebral Media/patología , Accidente Cerebrovascular Isquémico/patología , Ratones Endogámicos C57BL , Receptores de Progesterona/metabolismo , Accidente Cerebrovascular/patologíaRESUMEN
BACKGROUND: Toll-like receptor 3 (TLR3) plays an important role in the immune/inflammatory response in the nervous system and is a main pathological feature of Alzheimer's disease (AD). This study investigates the role of early activation of TLR3 in the pathophysiological process of AD. METHODS: In the experiment, the agonist of TLR3, Poly(I:C), was intraperitoneally injected into the APP/PS1 mouse model of AD and wild-type control mice starting from the age of 4 to 9 months. At the age of 14 months, behavioral tests were conducted. Western blot and immunohistochemistry staining were used to evaluate the level of amyloid ß-protein (Aß), the activation of inflammatory cells, and neuron loss. In addition, the levels of inflammatory cytokines were measured using a quantitative polymerase chain reaction. RESULTS: The results demonstrated that the early activation of TLR3 attenuated neuronal loss and neurobehavioral dysfunction. Moreover, the early activation of TLR3 reduced Aß deposition, inhibited the activation of microglia and astrocytes, and decreased the transcription of pro-inflammatory factors in the hippocampus. CONCLUSIONS: The results indicated that the activation of TLR3 by Poly (I:C) in the early stage of development of AD in a mouse model attenuated neuron loss and improved neurobehavioral functions. The underlying mechanisms could be attributed to its role in Aß clearance, the inhibition of glial cells, and the regulation of neuroinflammation in the hippocampus.
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Enfermedad de Alzheimer , Receptor Toll-Like 3 , Animales , Ratones , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides , Precursor de Proteína beta-Amiloide/genética , Modelos Animales de Enfermedad , Ratones Transgénicos , Presenilina-1/genética , Receptor Toll-Like 3/genética , Receptor Toll-Like 3/metabolismoRESUMEN
We investigated the functional role of eosinophil cationic protein (ECP) in regulating cardiomyogenesis using mouse P19CL6 embryonic carcinoma cells. ECP was confirmed to accelerate the cardiomyocyte differentiation of P19CL6 cells by enhancing the rate and area size of beating of cardiomyocyte and by facilitating the expression of cardiomyocyte-specific genes, such as GATA4 and α-MHC. Since cardiomyocyte differentiation in vivo is considered to follow mesoderm induction, the induction of Brachyury, a marker of mesoderm, was assessed. Brachyury expression was found to be enhanced after the addition of ECP. This enhancement was due to the stimulation of extracellular signal-regulated kinase (ERK)1/2 phosphorylation by ECP. In this context, treatment with SU5402, an inhibitor of fibroblast growth factor (FGF) receptor 1, suppressed Brachyury expression, phosphorylation of ERK1/2, and cardiomyocyte differentiation induced by ECP. We concluded that ECP might induce mesoderm differentiation through FGF signaling pathway and enhance subsequent cardiomyocyte differentiation in concert with dimethyl sulfoxide in P19CL6 cells. ECP may be a novel factor for cardiomyocyte differentiation, which should be very useful to prepare adequate numbers of cardiomyocytes for therapeutic cell transplantation.
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Células Madre de Carcinoma Embrionario/citología , Proteína Catiónica del Eosinófilo/metabolismo , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Animales , Diferenciación Celular , Línea Celular Tumoral , Dimetilsulfóxido/farmacología , Células Madre de Carcinoma Embrionario/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas Fetales/biosíntesis , Factor de Transcripción GATA4/biosíntesis , Ratones , Cadenas Pesadas de Miosina/biosíntesis , Fosforilación , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Pirroles/farmacología , Receptores de Factores de Crecimiento de Fibroblastos/antagonistas & inhibidores , Transducción de Señal , Proteínas de Dominio T Box/biosíntesisRESUMEN
Gastric cancer (GC) remains a major cause of cancer-related deaths. Increasing studies suggest that cancer development is accompanied by the deregulation of circular RNAs. We investigated the function of circ_0003159 in GC. The expression levels of circ_0003159, miR-221-3p/miR-222-3p and leukemia inhibitory factor receptor (LIFR) mRNA were measured by real-time quantitative polymerase chain reaction. Cell colony formation ability was assessed by colony formation assay, and cell viability was assessed by cell counting kit-8 assay. Cell apoptosis was assessed by flow cytometry assay and caspase3 activity. Cell migration and invasion were assessed by transwell assay. Glycolysis energy metabolism was assessed by 5'-triphosphate production, glucose uptake and lactate production. The protein levels of related marker proteins and LIFR were detected by western blot. The relationship between circ_0003159 and miR-221-3p/miR-222-3p, or LIFR and miR-221-3p/miR-222-3p was obtained from bioinformatics tools and verified by dual-luciferase reporter assay. A cancer tumorogenicity xenograft experiment in nude mice was conducted to determine the role of circ_0003159 in tumor growth by AGS cells. Our results showed that circ_0003159 expression was decreased in GC tissues and cells. Circ_0003159 overexpression sequestered GC cell viability, migration, invasion and glycolysis and induced cell apoptosis. MiR-221-3p and miR-222-3p were targets of circ_0003159, and the inhibition of miR-221-3p and miR-222-3p also blocked GC cell viability, migration, invasion and glycolysis and promoted cell apoptosis. LIFR was a common target of miR-221-3p and miR-222-3p. Interestingly, LIFR knockdown reversed the effects of circ_0003159 overexpression on GC cell behaviors. Circ_0003159 increased the expression level of LIFR by targeting miR-221-3p and miR-222-3p. The tumorigenicity assay showed that circ_0003159 overexpression inhibited tumor growth in vivo. In conclusion, circ_0003159 inhibited GC development in vitro and in vivo by enriching the level of LIFR via direct binding to miR-221-3p/miR-222-3p.
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MicroARNs , Neoplasias Gástricas , Animales , Proliferación Celular/genética , Humanos , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia , Ratones , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Receptores OSM-LIF , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologíaRESUMEN
This study investigated the expression of progesterone receptor membrane component 1 (pgrmc1) in the brains of male and female mice, and the effect of inhibiting pgrmc1 on neonatal hypoxic-ischemic (HI) cerebral injury in male mice. A mouse model of neonatal HI brain injury was established, and AG205, a specific antagonist of pgrmc1, was injected into the left lateral cerebral ventricle 1 h before HI. Histological staining, behavior testing, Western blots, and quantitative PCR (qPCR) were employed to evaluate pgrmc1 expression, brain damage, neurological function, and molecular mechanisms. Results demonstrated that the mRNA and protein levels of pgrmc1 increased significantly in the cortex and hippocampus 72 h after HI without sex differences. The inhibition of pgrmc1 exacerbated the neonatal brain damage in the acute stage of HI in male mice as seen in the increase in brain water content, infarction area, and neuronal death. Inhibition of pgrmc1 also aggravated the neurological dysfunction and anxiety induced by HI brain injury. In addition, inhibition of pgrmc1 activated the NF-kB signaling and NF-κB-mediated cytokines, and inhibited BDNF/PI3K/AKT pathway in the brains of the newborn HI mice. The results indicated that pgrmc1 inhibition exacerbated the brain damage in newborn male mice subjected to HI by activating IκBα/NFκB signaling and inhibiting BDNF/PI3K/Akt pathway.
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Hipoxia-Isquemia Encefálica/metabolismo , Hipoxia-Isquemia Encefálica/patología , Proteínas de la Membrana/metabolismo , Receptores de Progesterona/metabolismo , Animales , Animales Recién Nacidos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Caracteres Sexuales , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: This study aimed to explore relevant factors of hemorrhagic contusions following decompressive craniotomy (DC) in traumatic brain injury (TBI) and create an artificial neural network (ANN) prediction model of the risk factors of hemorrhagic contusions. METHODS: This study analyzed 425 patients with TBI who underwent DC in the Neurosurgery Department of Shaoxing People's Hospital between 2009 and 2014. Patients were divided into two groups according to the first postoperative CT scans: hemorrhage group and non-hemorrhage group. Gender, age, preoperative situations (Initial Rotterdam CT Score, GCS Score, pupillary response, laboratory data and preoperative hematoma), the time gap between trauma and DC, postoperative CT scans, and Glasgow Outcome Scale (GOS) scores were recorded. ANN was used to predict hematoma. Correlation analysis was used to state the relationship between increased hemorrhage volumes and GOS scores. RESULTS: The ANN prediction model was established. This model included 11 parameters: initial Rotterdam CT score, GCS score, C-reactive protein, age, the time gap between trauma and DC, pupillary response, platelet count, bone-flap size, glucose level, hernia magnitude and preoperative hematoma volume. The overall predictive accuracy of the model was 73.0%. CONCLUSIONS: Initial Rotterdam CT scores and GCS scores may predict the risk of expansion contusions following DC. The ANN prediction model has a high accuracy to forecast hemorrhage.
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Lesiones Traumáticas del Encéfalo , Contusiones , Craniectomía Descompresiva , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/cirugía , Craneotomía , Hematoma/etiología , Hematoma/cirugía , Humanos , Redes Neurales de la Computación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Traumatic brain injury (TBI) generates excess reactive oxygen species (ROS), which can exacerbate secondary injury and result in disability and death. Secondary injury cascades can trigger the release of uncontrolled ROS into the surrounding normal brain tissue, forming an extended pool of ROS, which leads to massive neuronal death. Here, we developed an injectable, post-trauma microenvironment-responsive, ROS depletion hydrogel embedded curcumin (Cur) (TM/PC) for reducing ROS levels in damaged brain tissue to promote the regeneration and recovery of neurons. Hydrogel was composed of three parts: (1) Hydrophobic poly (propylene sulfide)120 (PPS120) was synthesized, with a ROS quencher and H2O2-responsive abilities, to embed Cur. (2) Matrix metalloproteinase (MMP)-responsive triglycerol monostearate (TM) was used to cover the PPS120 to form a TM/P hydrogel. (3) Cur could further eradicate the ROS, promoting the regeneration and recovery of neurons. In two postoperative TBI models, TM/PC hydrogel effectively responded the TBI surgical environment and released drug. TM/PC hydrogel significantly depleted ROS and reduced brain edema. In addition, reactive astrocytes and activated microglia were decreased, growth-associated protein 43 (GAP43) and doublecortin (DCX) were increased, suggested that TM/PC hydrogel had the strongest anti-inflammatory effect and effectively promoted nerve regeneration after TBI. This study provides new information for the management of TBI to prevent the secondary spread of damage.
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Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Lesiones Encefálicas/tratamiento farmacológico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Humanos , Hidrogeles , Peróxido de Hidrógeno , Especies Reactivas de OxígenoRESUMEN
OBJECTIVE: To analyze the correlative factors of traumatic embolism in superficial cerebral vein and explore their corresponding treatments. METHODS: A total of 74 cases were divided into 3 groups according to their injury mechanisms. Group A: traumatic brain injury in superficial cerebral vein with cerebral contusion, acute intracerebral hematoma and subdural hematoma in the same place; Group B: traumatic brain injury in superficial cerebral vein with acute intracerebral hematoma, subdural hematoma and skull fracture in the same place; Group C: traumatic brain injury in superficial cerebral vein with acute subdural hematoma and skull fracture in the same place, without cerebral contusion or acute intracerebral hematoma. They were divided into different groups according to gender, age, pre-operative GCS and cerebral hernia. RESULTS: Among 74 cases, 28, 39 and 7 cases belonged to groups A, B and C respectively. There was significant difference among injured veins in three groups (P < 0.01). Cerebral infarction was found in 37 cases in groups A and B while only 2 cases in group C. Cerebral infarction had no correlation with sex, age, pre-operative GCS and cerebral hernia. CONCLUSION: Injuries in superficial cerebral vein are mainly caused by skull fracture, contre-coup injury and shearing force. Cerebral infarction often exists if there is cerebral contusion. It is necessary to protect injured primary superficial cerebral veins and ambient venous network, remove intracranial hematoma and large bone flap to reduce intracranial hypertension and dilute blood post-operatively to prevent venous embolism.
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Venas Cerebrales/patología , Embolia Intracraneal/etiología , Heridas y Lesiones/complicaciones , Adolescente , Adulto , Anciano , Infarto Encefálico/complicaciones , Lesiones Encefálicas/complicaciones , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fracturas Craneales/complicaciones , Adulto JovenRESUMEN
Toll-like receptor-2 (TLR2), a member of the TLR family, plays an important role in the initiation and regulation of immune/inflammation response, which is a critical mechanism underlying Alzheimer's disease (AD). To clarify the role of TLR2 in the pathological process of AD, in the present study, TLR2 knockout plus APPswe/PSEN1dE9 transgenic mice (AD-TLR2KO) were generated. Neurobehavioral tests and brain MRI scan were conducted on mice at the age of 12 months. Additionally, neuron loss was evaluated using NeuN staining. Amyloid ß protein (Aß), glial fibrillary acidic protein (GFAP), endogenous ligands for TLR2, and the activation of downstream signaling of TLR2 in mouse brains were detected by immunohistochemistry and Western blots. The results demonstrated that TLR2 deficit induced learning disabilities, decreased spontaneous activity, increased anxiety and depression, and led to white matter damage (WMD), brain atrophy, loss of neurons, and glial activation. Moreover, TLR2 deficit aggravated impaired neurobehavioral functions and WMD in AD mice, but did not affect the Aß deposition in mouse brains. Our data indicate that the genomic deletion of TLR2 impairs neurobehavioral functions, induces WMD and brain atrophy, and increases the activation of astrocytes, which in turn aggravate the symptoms of AD through a non-Aß mechanism.
Asunto(s)
Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/psicología , Receptor Toll-Like 2/genética , Sustancia Blanca/patología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/metabolismo , Animales , Ansiedad/genética , Disfunción Cognitiva/genética , Depresión/genética , Imagen de Difusión Tensora , Modelos Animales de Enfermedad , Femenino , Proteína Ácida Fibrilar de la Glía/metabolismo , Masculino , Aprendizaje por Laberinto , Ratones Noqueados , Actividad Motora/genética , Plasticidad Neuronal , Sustancia Blanca/diagnóstico por imagenRESUMEN
OBJECTIVE: To analyze the changing trends of frequency and localization of gastric cancers arising from the gastric cardia, corpus and antrum during the past 14 years in population of the high incidence area of esophageal and gastric carcinoma in Hebei province, China. METHODS: The clinicopathological data of 4334 cases of gastric carcinomas among the local residents of Cixian and Zanhuang counties, initially diagnosed in our department from 1993 to 2006, were retrospectively analyzed. The proportion of gastric carcinomas arising from the gastric cardia, corpus and antrum in different years and in patients with different sex and ages were analyzed and compared, and the changing trends of the frequency of gastric carcinoma arising from different sites of the stomach were statistically analyzed. RESULTS: Among all the 4334 gastric carcinomas, gastric cardia carcinoma accounted for 68.0%, significantly higher than that of corpus (24.2%) and antrum (7.9%; chi(2) = 124.396, P < 0.0001). An increasing tendency in the proportion of gastric cardia carcinoma from 1993 to 2006 was seen. The percentage of cardiac carcinoma in the high incidence area of esophageal carcinoma (Cixian county) was higher than that in the high incidence area of gastric cancer (Zanhuang county) (71.2% vs. 51.2%; chi(2) = 109.648, P < 0.0001). The increase in the incidence of cardiac carcinoma in Cixian county was mainly due to the increase of cardiac carcinoma from 1993 to 2006, while the contributing factor for the increase in the proportion of cardiac carcinomas was resulted from the decrease of incidence of antrum carcinoma in Zanhuang county during the same period. The occurring site of gastric carcinoma was related with age of patients (chi(2) = 58.380, P < 0.0001). The percentage of carcinoma of the gastric body was highest in < 50 year age group, while that in the gastric cardia was highest in 61 - 70 year age group (71.6%). CONCLUSION: The major occurring site of gastric carcinoma is the gastric cardia among the local residents in population of the high incidence areas of esophageal and gastric carcinomas during the past 14 years in Hebei province, China. The increasing trend of cardiac carcinoma and decreasing trend of corpus carcinoma in Cixian county and antrum carcinoma in Zanhuang county will be maintained in the coming years if the epidemiological conditions will not be changed.
Asunto(s)
Cardias/patología , Neoplasias Gástricas/epidemiología , Estómago/patología , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Niño , China/epidemiología , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Antro Pilórico/patología , Estudios Retrospectivos , Neoplasias Gástricas/patología , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND AND STUDY AIMS: Both high and low wall shear stress (WSS) play important roles in the development and rupture of intracranial aneurysms (IAs). This study aimed to determine the morphological factors that affect WSS in the IA and the parent artery. MATERIAL AND METHODS: We studied a total of 66 IAs with three-dimensional imaging. Computational fluid dynamics (CFD) models were constructed and used to characterize the hemodynamics quantitatively. Aneurysms were grouped according to the mean neck width. The associations among hemodynamics and morphology were analyzed. RESULTS: Aspect ratio was correlated to lowest WSS (r = - 0.576), aneurysm-to-parent vessel (A-P) WSS ratio (r = - 0.500), and lowest-parent vessel (L-P) WSS ratio (r = - 0.575). Height-to-width ratio and height were correlated to WSS. Mean aneurysm WSS (p = 0.023), lowest WSS (p < 0.0001), highest-to-lowest WSS ratio (p = 0.004), L-P WSS ratio (p < 0.0001), highest-parent vessel (H-P) WSS ratio (p = 0.008), A-P WSS ratio (p < 0.001), and height (p < 0.001) were different between the two groups of aneurysms that were divided by the relationship between the diameters of the aneurysms and the necks. Multivariable analysis showed that the lowest WSS (p = 0.028) and A-P WSS ratio (p = 0.001) were independently associated with neck width. CONCLUSION: Morphological characteristics are associated with IA and parent vessel WSS. Aneurysms with different neck widths have different hemodynamics. These results could help in understanding the progression of IA and in building predictive models for IA rupture.