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Microglial HO-1 regulates iron metabolism in the brain. Intracerebral haemorrhage (ICH) shares features of ferroptosis and necroptosis; hemin is an oxidized product of haemoglobin from lysed red blood cells, leading to secondary injury. However, little is known about the underlying molecular mechanisms attributable to secondary injury by hemin or ICH. In this study, we first show that FoxO3a was highly co-located with neurons and microglia but not astrocytes area of ICH model mice. Hemin activated FoxO3a/ATG-mediated autophagy and HO-1 signalling resulting in ferroptosis in vitro and in a mice model of brain haemorrhage. Accordingly, autophagy inhibitor Baf-A1 or HO-1 inhibitor ZnPP protected against hemin-induced ferroptosis. Hemin promoted ferroptosis of neuronal cells via FoxO3a/ATG-mediated autophagy and HO-1 signalling pathway. Knock-down of FoxO3a inhibited autophagy and prevented hemin-induced ferroptosis dependent of HO-1 signalling. We first showed that hemin stimulated microglial FoxO3a/HO-1 expression and enhanced the microglial polarisation towards the M1 phenotype, while knockdown of microglial FoxO3a inhibited pro-inflammatory cytokine production in microglia. Furthermore, the microglia activation in the striatum showed significant along with a high expression level of FoxO3a in the ICH mice. We found that conditional knockout of FoxO3a in microglia in mice alleviated neurological deficits and microglia activation as well as ferroptosis-induced striatum injury in the autologous blood-induced ICH model. We demonstrate, for the first time, that FoxO3a/ATG-mediated autophagy and HO-1 play an important role in microglial activation and ferroptosis-induced striatum injury of ICH, identifying a new therapeutic avenue for the treatment of ICH.
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Lesiones Encefálicas , Ferroptosis , Ratones , Animales , Microglía/metabolismo , Hemo-Oxigenasa 1/metabolismo , Hemina , Hemorragia Cerebral/complicaciones , Autofagia , Lesiones Encefálicas/metabolismoRESUMEN
Chondrosarcoma is a malignant bone tumor that emerges from abnormalities in cartilaginous tissue and is related with lung metastases. Nicotinamide phosphoribosyltransferase (NAMPT) is an adipocytokine reported to enhance tumor metastasis. Our results from clinical samples and the Gene Expression Omnibus data set reveal that NAMPT levels are markedly higher in chondrosarcoma patients than in normal individuals. NAMPT stimulation significantly increased lysyl oxidase (LOX) production in chondrosarcoma cells. Additionally, NAMPT increased LOX-dependent cell migration and invasion in chondrosarcoma by suppressing miR-26b-5p generation through the c-Src and Akt signaling pathways. Overexpression of NAMPT promoted chondrosarcoma metastasis to the lung in vivo. Furthermore, knockdown of LOX counteracted NAMPT-facilitated metastasis. Thus, the NAMPT/LOX axis presents a novel target for treating the metastasis of chondrosarcoma.
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BACKGROUND: Aortic dissection (AD) is a macrovascular disease which is pathologically characterized by aortic media degeneration.This experiment aims to explore how iron deficiency (ID) affects the function of vascular smooth muscle cell (VSMC) and participates in the occurrence and development of AD by regulating gene expression. METHODS: The relationship between iron and AD was proved by Western-blot (WB) and immunostaining experiments in human and animals. Transcriptomic sequencing explored the transcription factors that were altered downstream. WB, flow cytometry and immunofluorescence were used to demonstrate whether ID affected HIF1 expression through oxygen transport. HIF1 signaling pathway and phenotypic transformation indexes were detected in cell experiments. The use of the specific HIF1 inhibitor PX478 further demonstrated that ID worked by regulating HIF1. RESULTS: The survival period of ID mice was significantly shortened and the pathological staining results were the worst. Transcriptomic sequencing indicated that HIF1 was closely related to ID and the experimental results indicated that ID might regulate HIF1 expression by affecting oxygen balance. HIF1 activation regulates the phenotypic transformation of VSMC and participates in the occurrence and development of AD in vivo and in vitro.PX478, the inhibition of HIF1, can improve ID-induced AD exacerbation.
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Disección Aórtica , Músculo Liso Vascular , Miocitos del Músculo Liso , Oxígeno , Transducción de Señal , Animales , Humanos , Masculino , Ratones , Disección Aórtica/metabolismo , Disección Aórtica/etiología , Disección Aórtica/genética , Disección Aórtica/patología , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Factor 1 Inducible por Hipoxia/metabolismo , Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Deficiencias de Hierro , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/metabolismo , Oxígeno/metabolismo , FenotipoRESUMEN
The contaminant status, spatial distribution, partitioning behavior, and ecological risks of 26 legacy and emerging perfluoroalkyl and polyfluoroalkyl substances (PFASs) in Laizhou Bay, China were investigated. The concentrations of ∑PFASs in surface and bottom seawater ranged from 37.2 to 222 ng/L and from 34.2 to 305 ng/L with an average of 116 ± 62.7 and 138 ± 93.8 ng/L, respectively. There were no significant differences in the average concentrations between the surface and bottom seawater (P > 0.05). Perfluorooctanoic acid (PFOA) and short-chain PFASs dominated the composition of PFASs in seawater. The concentrations of ∑PFASs in sediments ranged from 0.997 to 7.21 ng/g dry weight (dw), dominated by perfluorobutane sulfonate (PFBS), perfluorobutanoic acid (PFBA), and long-chain PFASs. The emerging alternatives of perfluoro-1-butane-sulfonamide (FBSA) and 6:2 fluorotelomer sulfonic acid (6:2 FTSA) were detected for the first time in Laizhou Bay. The ∑PFASs in seawater in the southwest of the bay were higher than those in the northeast of the bay. The ∑PFASs in sediments in the northeast sea area were higher than those in the inner area of the bay. Log Kd and log Koc values increased with increasing carbon chain length for PFASs compounds. Ecological risk assessments indicated a low ecological risk associated with HFPO-DA but a moderate risk associated with PFOA contamination in Laizhou Bay. Positive matrix factorization (PMF) analysis revealed that fluoropolymer manufacturing, metal plating plants, and textile treatments were identified as major sources contributing to PFASs contamination.
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Ácidos Alcanesulfónicos , Caprilatos , Fluorocarburos , Contaminantes Químicos del Agua , Bahías , Contaminantes Químicos del Agua/análisis , Monitoreo del Ambiente , Fluorocarburos/análisis , China , Medición de Riesgo , Ácidos Alcanesulfónicos/análisisRESUMEN
PURPOSE: This study aimed to consolidate the evidence regarding the prognostic influence of sarcopenia in degenerative lumbar spine surgeries. METHODS: A literature search of public databases was conducted up to Nov 15, 2023 using combinations of the key words "sarcopenia" and "lumbar spine surgery". Eligible studies were those that focused on adults undergoing decompression or fusion surgery for degenerative lumbar spine diseases, and compared the outcomes between patients with and without preoperative sarcopenia. Primary outcomes were change in ODI and back and leg pain VAS pain scores. Secondary outcomes were changes in Eq. 5D, JOA, SFHS-p scores, and LOS. RESULTS: Ultimately, nine retrospective studies with a total of 993 patients were included. Sarcopenic patients exhibited significantly worse functional improvement as assessed by ODI compared to non-sarcopenic patients (pooled standardized mean difference [pSMD] = 0.53, 95% confidence interval [CI]: 0.17-0.90). Back pain (pSMD = 0.31, 95% CI:0.15-0.47) and leg pain (pSMD = 0.21, 95% CI:0.02 - 0.39) improvement were also less in sarcopenic patients. Non-sarcopenic patients had greater improvements in Eq. 5D (pSMD = 0.25) and SFHS-p (pSMD = 0.39), and shorter LOS (pSMD = 0.62). CONCLUSIONS: As compared to patients without sarcopenia, those with sarcopenia undergoing lumbar spine surgery for degenerative diseases have lower improvements in functional ability, quality of life, physical health, pain relief and extended hospitalization compared to those without sarcopenia.
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In this manuscript, we present a novel deployment protection method aimed at safeguarding aeronautical radio altimeters (RAs) from interference caused by fifth-generation (5G) telecommunication base stations (BSs). Our methodology involves an integrated interference model for defining prohibited zones and utilizes power control and angle shutoff methods to mitigate interference. First, to ensure reliable protection, we define both horizontal and vertical prohibited zones and investigate their variations to immunize RA against 5G interference. Second, we validate the effectiveness of the model in various operational scenarios, analyzing the influence of factors such as base station types, antenna parameters, flight altitude, and aircraft attitudes to cover a wide range of real-world scenarios. Third, to mitigate interference, we propose and analyze the power control and angle shutoff methods through simulation for the RMa prohibited zone. Our results demonstrate the efficacy of the deployment protection method in safeguarding RAs from 5G interference, providing guidance for interference protection during civil aviation operations and base station deployment near airports.
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Chondrosarcoma is a malignant bone tumor that arises from abnormalities in cartilaginous tissue and is associated with lung metastases. Lymphangiogenesis plays an essential role in cancer metastasis. Visfatin is an adipokine reported to enhance tumor metastasis, but its relationship with VEGF-D generation and lymphangiogenesis in chondrosarcoma remains undetermined. Our results from clinical samples reveal that VEGF-D levels are markedly higher in chondrosarcoma patients than in normal individuals. Visfatin stimulation promotes VEGF-D-dependent lymphatic endothelial cell lymphangiogenesis. We also found that visfatin induces VEGF-D production by activating HIF-1α and reducing miR-2277-3p generation through the Raf/MEK/ERK signaling cascade. Importantly, visfatin controls chondrosarcoma-related lymphangiogenesis in vivo. Therefore, visfatin is a promising target in the treatment of chondrosarcoma lymphangiogenesis.
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Neoplasias Óseas , Condrosarcoma , Subunidad alfa del Factor 1 Inducible por Hipoxia , Linfangiogénesis , MicroARNs , Nicotinamida Fosforribosiltransferasa , Factor D de Crecimiento Endotelial Vascular , Humanos , Condrosarcoma/metabolismo , Condrosarcoma/genética , Condrosarcoma/patología , Linfangiogénesis/genética , MicroARNs/genética , MicroARNs/metabolismo , Nicotinamida Fosforribosiltransferasa/metabolismo , Nicotinamida Fosforribosiltransferasa/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Factor D de Crecimiento Endotelial Vascular/metabolismo , Factor D de Crecimiento Endotelial Vascular/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Neoplasias Óseas/genética , Animales , Regulación Neoplásica de la Expresión Génica , Línea Celular Tumoral , Ratones , Citocinas/metabolismo , Masculino , Femenino , Sistema de Señalización de MAP QuinasasRESUMEN
Background and Objectives: Adolescent idiopathic scoliosis (AIS) is a prevalent three-dimensional spinal disorder, with a multifactorial pathogenesis, including genetics and environmental aspects. Treatment options include non-surgical and surgical treatment. Surgical interventions demonstrate positive outcomes in terms of deformity correction, pain relief, and improvements of the cardiac and pulmonary function. Surgical complications, including excessive blood loss and neurologic deficits, are reported in 2.27-12% of cases. Navigation-assisted techniques, such as the O-arm system, have been a recent focus with enhanced precision. This study aims to evaluate the results and complications of one-stage posterior instrumentation fusion in AIS patients assisted by O-arm navigation. Materials and Methods: This retrospective study assesses 55 patients with AIS (12-28 years) who underwent one-stage posterior instrumentation correction supported by O-arm navigation from June 2016 to August 2023. We examined radiological surgical outcomes (initial correction rate, loss of correction rate, last follow-up correction rate) and complications as major outcomes. The characteristics of the patients, intraoperative blood loss, operation time, number of fusion levels, and screw density were documented. Results: Of 73 patients, 55 met the inclusion criteria. The average age was 16.67 years, with a predominance of females (78.2%). The surgical outcomes demonstrated substantial initial correction (58.88%) and sustained positive radiological impact at the last follow-up (56.56%). Perioperative complications, including major and minor, occurred in 18.18% of the cases. Two patients experienced a major complication. Blood loss (509.46 mL) and operation time (402.13 min) were comparable to the literature ranges. Trend analysis indicated improvements in operation time and blood loss over the study period. Conclusions: O-arm navigation-assisted one-stage posterior instrumentation proves reliable for AIS corrective surgery, achieving significant and sustained positive radiological outcomes, lower correction loss, reduced intraoperative blood loss, and absence of implant-related complications. Despite the challenges, our study demonstrates the efficacy and maturation of this surgical approach.
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Cifosis , Tornillos Pediculares , Escoliosis , Fusión Vertebral , Cirugía Asistida por Computador , Femenino , Humanos , Adolescente , Masculino , Escoliosis/cirugía , Escoliosis/complicaciones , Tornillos Pediculares/efectos adversos , Estudios Retrospectivos , Pérdida de Sangre Quirúrgica , Fusión Vertebral/métodos , Imagenología Tridimensional , Tomografía Computarizada por Rayos X/métodos , Cifosis/cirugía , Complicaciones Posoperatorias/etiología , Resultado del Tratamiento , Vértebras TorácicasRESUMEN
BACKGROUND: Heart transplantation (HT) has been approved as an optimal therapeutic regimen for patients with terminal-stage cardiac failure. However, cold ischaemiaâreperfusion (I/R) injury remains an unavoidable and outstanding challenge, which is a major factor in early graft dysfunction and an obstacle to long-term survival in HT. Cold I/R injury induces cardiac graft injury by promoting mitochondrial dysfunction and augmenting free radical production and inflammatory responses. We therefore designed a mitochondrion-targeted nanocarrier loaded with Coenzyme Q10 (CoQ10) (CoQ10@TNPs) for treatment of cold I/R injury after cardiac graft in a murine heterotopic cardiac transplantation model. METHODS: Hybrid nanoparticles composed of CaCO3/CaP/biotinylated-carboxymethylchitosan (CaCO3/CaP/BCMC) were synthesized using the coprecipitation method, and the mitochondria-targeting tetrapeptide SS31 was incorporated onto the surface of the hybrid nanoparticles through biotin-avidin interactions. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis were used for characterisation. In vitro, the hypoxia-reoxygenation model of H9c2 cells was employed to replicate in vivo cold I/R injury and treated with CoQ10@TNPs. The impact of CoQ10@TNPs on H9c2 cell injury was assessed by analysis of oxidative damage and apoptosis. In vivo, donor hearts (DHs) were perfused with preservation solution containing CoQ10@TNPs and stored in vitro at 4 °C for 12 h. The DHs were heterotopically transplanted and analysed for graft function, oxidative damage, apoptosis, and inflammatory markers 1 day post-transplantation. RESULTS: CoQ10@TNPs were successfully synthesized and delivered CoQ10 to the mitochondria of the cold ischaemic myocardium. In vitro experiments demonstrated that CoQ10@TNPs was taken up by H9c2 cells at 4 °C and localized within the mitochondria, thus ameliorating oxidative stress damage and mitochondrial injury in cold I/R injury. In vivo experiments showed that CoQ10@TNPs accumulated in DH tissue at 4 °C, localized within the mitochondria during cold storage and improved cardiac graft function by attenuating mitochondrial oxidative injury and inflammation. CONCLUSIONS: CoQ10@TNPs can precisely deliver CoQ10 to the mitochondria of cold I/R-injured cardiomyocytes to effectively eliminate mitochondrial reactive oxygen species (mtROS), thus reducing oxidative injury and inflammatory reactions in cold I/R-injured graft tissues and finally improving heart graft function. Thus, CoQ10@TNPs offer an effective approach for safeguarding cardiac grafts against extended periods of cold ischaemia, emphasizing the therapeutic potential in mitigating cold I/R injury during HT. These findings present an opportunity to enhance existing results following HT and broaden the range of viable grafts for transplantation.
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Quitosano , Lesiones Cardíacas , Trasplante de Corazón , Daño por Reperfusión , Ratones , Humanos , Animales , Trasplante de Corazón/métodos , Quitosano/farmacología , Quitosano/metabolismo , Donantes de Tejidos , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Mitocondrias , Miocitos Cardíacos/metabolismoRESUMEN
Depression is a severe mental disorder among public health issues. Researchers in the field of mental health and clinical psychiatrists have long been faced with difficulties in slow treatment cycles, high recurrence rates, and lagging efficacy. These obstacles have forced us to seek more advanced and effective treatments. Research has shown that novel drug delivery strategies for natural medicinal plants can effectively improve the utilization efficiency of the active molecules in these plants and therefore improve their efficacy. Currently, with the development of treatment technologies and the constant updating of novel drug delivery strategies, the addition of natural medicinal antidepressant therapy has given new significance to the study of depression treatment against the background of novel drug delivery systems. Based on this, this review comprehensively evaluates and analyses the research progress in novel drug delivery systems, including nanodrug delivery technology, in intervention research strategies for neurological diseases from the perspective of natural medicines for depression treatment. This provided a new theoretical foundation for the development and application of novel drug delivery strategies and drug delivery technologies in basic and clinical drug research fields.
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Plantas Medicinales , Humanos , Sistemas de Liberación de Medicamentos , Antidepresivos/uso terapéuticoRESUMEN
Plasmonic-enhanced photocatalysis using visible light is considered a promising strategy for pollution photodegradation. However, there is still a lack of comprehensive and quantitative understanding of the underlying mechanisms and interactions involved. In this study, we employed a two-step process to fabricate arrays of ZnO nanosheets decorated with Au nanoparticles (Au-ZnO NS). Various characterization techniques were used to examine the morphological, structural, and chemical properties of the fabricated Au-ZnO NS array. Furthermore, we systematically investigated the photocatalytic degradation of methyl orange under visible light irradiation using Au-ZnO NS arrays prepared with varying numbers of photochemical reduction cycles. The results indicated that as the number of photochemical reduction cycles increased, the photodegradation efficiency initially increased but subsequently decreased. Under visible light irradiation, the Au-ZnO NS array obtained via four cycles of photochemical reduction exhibits the highest photocatalytic degradation rate of methyl orange 0.00926 min-1, which is six times higher than that of the ZnO NS array. To gain a better understanding of the plasmonic effect on photodegradation performance, we utilized electromagnetic simulations to quantitatively investigate the enhancement of electric fields in the Au-ZnO NS array. The simulations clearly presented the nonlinear dependencies of electric field intensity on the distribution of Au nanoparticles and the wavelength of radiation light, leading to a nonlinear enhancement of hot electron injection and eventual plasmonic photodegradation. The simulated model, corresponding to four cycles of photochemical reduction, exhibits the highest electric field intensity at 550 nm, which can be attributed to its strong plasmonic effect. This work provides mechanistic insights into plasmonic photocatalysts for utilizing visible light and represents a promising strategy for the rational design of high-performance visible light photocatalysts.
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Background: Spinal fusion is a common surgery, in which vertebrae are fused to restore spinal stability and eliminate pain during movement. The use of an interbody cage facilitates spinal fusion. However, complete cage migration into the dura matter rarely occurs and can be challenging to manage. Case Presentation: A 44-year-old man presented at our spine center with a history of incomplete paraplegia and cauda equina syndrome that had lasted for 2 years and 4 months. This condition developed after he underwent six lumbar spine surgeries to address lower back pain and right-sided sciatica. A structural allograft kidney-shaped cage was found completely within the dura at the level of the L3 vertebra. Durotomy, cage retrieval, and pedicle screw fixation from the L2 to L4 vertebrae were performed. Numbness in both lower limbs markedly decreased within several days of the operation. After four months following the progressive physical therapy, the patient could partially control both urination and defecation. Five months postoperatively, he could stand with slight assistance. Conclusions: Complete intradural cage migration is a rare and serious complication. To the best of our knowledge, this is the first reported case with such a condition in the literature. Even if treatment is delayed, surgical intervention may salvage the remaining neurologic function and may even lead to partial recovery.
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Tornillos Pediculares , Fusión Vertebral , Masculino , Humanos , Adulto , Fusión Vertebral/efectos adversos , Vértebras Lumbares/cirugía , Procedimientos NeuroquirúrgicosRESUMEN
FoxO transcription factors (FoxOs) have recently been shown to protect against chondrocyte dysfunction and modulate cartilage homeostasis in osteoarthritis. The mechanism underlying of FoxOs regulate chondrocyte differentiation remains unknown. Runt related transcription factor 1 (RUNX1) mediated both chondrocyte and osteoblast differentiation. Our data showed that FoxO3a and RUNX1 are co-expressed in ATDC5 cells and undifferentiated mesenchyme cells and have similar high levels in chondrocytes undergoing transition from proliferation to hypertrophy. Overexpression of FoxO3a in ATDC5 cells or mouse mesenchymal cells resulted in a potent induction of the chondrocyte differentiation markers. Knockdown FoxO3a or RUNX1 potently inhibits the expressions of chondrocyte differentiation markers, including Sox9, Aggrecan, Col2, and hypertrophic chondrocyte markers including RUNX2, ColX, MMP13 and ADAMTs-5 in ATDC5 cells. Co-immunoprecipitation showed that FoxO3a binds the transcriptional regulator RUNX1. Immunohistochemistry showed that FoxO3a and RUNX1 are highly co-expressed in the proliferative chondrocytes of the growth plates in the hind limbs of newborn mice. Collectively, we revealed that FoxO3a cooperated with RUNX1 promoted chondrocyte differentiation through enhancing both early chondrogenesis and terminal hypertrophic of the chondrogenic progenitor cells, indicating FoxO3a interacting with RUNX1 may be a therapeutic target for the treatment of osteoarthritis and other bone diseases.
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Condrogénesis , Subunidad alfa 2 del Factor de Unión al Sitio Principal/metabolismo , Proteína Forkhead Box O3/metabolismo , Células Madre/metabolismo , Animales , Animales Recién Nacidos , Diferenciación Celular , Línea Celular , Condrocitos/metabolismo , Condrocitos/patología , Femenino , Placa de Crecimiento/metabolismo , Hipertrofia , Articulación de la Rodilla/patología , Masculino , Ratones , Unión ProteicaRESUMEN
BACKGROUND: Aortic dissection (AD) is a macrovascular disease which is pathologically characterized by aortic media degeneration (AMD). Our team's previous research found that iron deficiency (ID) promoted the formation of AMD through presentative research. In this study, we aimed to investigate the underlying mechanism of ID promoting AMD formation. METHODS: The human aortic tissues were harvested from AD patients and organ donors. ApoE-/- mice were simultaneously given AngII infusion and low-iron feed to investigate the relationship between ID and AD. The IRE1-XBP1-CHOP signal axis of endoplasmic reticulum (ER) stress was selectively inhibited with 4µ8C. Iron contents were detected by Perls staining. The expression of iron metabolism and ER stress-relative proteins were analyzed by IF and western blotting. Apoptosis rates of aortic tissue and ASMCs were detected by TUNEL staining and flow cytometry, and ROS content was also measured by the flow cytometry. RESULTS: ID was accompanied by ER stress in patients with AD. Among the three signaling pathways of ER stress in ID-induced AMD, proteins of IRE1, PERK and ATF6 signaling pathways were up-regulated by 2.65 times, 1.14 times and 1.24 times, respectively. ID was positively related to ER stress, mitochondrial oxidative stress and aortic media apoptosis in vivo and in vitro assays, while 4µ8C reversed the severity of ER stress and AMD. CONCLUSIONS: ID could activate ER stress by eliciting mitochondrial oxidative stress to activate the IRE1-XBP1-CHOP signaling pathway in the ER, which accelerated the apoptosis of ASMCs in aortic media, thus promoting the formation of AMD.
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Estrés del Retículo Endoplásmico , Deficiencias de Hierro , Animales , Apoptosis , Humanos , Hierro , Ratones , Ratones Noqueados para ApoE , Proteínas Serina-Treonina Quinasas , Transducción de SeñalRESUMEN
Controllably accumulating and delivering nanoparticles (NPs) into specific locations are a central theme of nano-engineering and important for targeted therapy or bacteria removal. Here we present a technique allowing bidirectional accumulation, directional delivery and release of nanoparticles through two 980-nm-wavelength counter-propagating evanescent waves in an optical nanofiber (NF). Using 713-nm-diameter polystyrene NPs suspension and an 890-nm-diameter NF as an example, we experimentally and theoretically demonstrate that the NPs delivered along the NF surface in opposite directions are accumulated into the region where the scattering loss of the NPs is maximum, and about 90% of the incident optical field from both ends of the NF can be coupled into the region. Moreover, the accumulation region can be controlled by altering the incident optical power ratio of the two counter-propagating laser beams, while the accumulated NPs can be delivered and then released into the specific locations by turning off the two lasers.
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Nanofibras , Nanopartículas , Rayos Láser , Poliestirenos , SuspensionesRESUMEN
Val-Val-Tyr-Pro (VVYP) peptide is one of the main active components of Globin digest (GD). Our previous studies indicated that VVYP could protect against acetaminophen and carbon tetrachloride-induced acute liver failure in mice and decrease blood lipid level. However, the effects and underlying mechanisms of VVYP in the treatment of non-alcoholic steatohepatitis (NASH) have not been discovered. Our present study was designed to investigate the preventive effect of VVYP on NASH and its underlying specific mechanisms. We found that VVYP inhibited the cytotoxicity and lipid accumulation in L-02 cells that were exposed to a mixture of free fatty acid (FFA). VVYP effectively alleviated the liver injury induced by methionine-choline-deficient (MCD) diet, demonstrated by reducing the levels of serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/triglycerides (TG)/non-esterified fatty acids (NEFA) and improving liver histology. VVYP decreased expression levels of lipid synthesis-related genes and reduced levels of the proinflammation cytokines in the liver of mice fed by MCD diet. Moreover, VVYP inhibited the increased level of LPS and reversed the liver mitochondria dysfunction induced by MCD diet. Meanwhile, VVYP significantly increased the abundance of beneficial bacteria such as Eubacteriaceae, coriobacteriacease, Desulfovibrionaceae, S24-7 and Bacteroidia in high-fat diet (HFD)-fed mice, however, VVYP reduced the abundance of Lactobacillus. Moreover, VVYP conferred the protective effect of intestinal barrier via promoting the expression of the mucins and tight junction (TJ)-associated genes and inhibited subsequent liver inflammatory responses. These results indicated that the protective role of VVYP on NASH is mediated by modulating gut microbiota imbalance and related gut-liver axis activation. VVYP might be a promising drug candidate for NASH.
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Retroalimentación Fisiológica/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/metabolismo , Hígado/metabolismo , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Oligopéptidos/farmacología , Animales , Antiinflamatorios/farmacología , Biomarcadores , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Modelos Animales de Enfermedad , Masculino , Ratones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/patología , Sustancias Protectoras/farmacologíaRESUMEN
BACKGROUND: Heart transplantation (HT) is the only effective treatment for end-stage heart failure because it can effectively improve the survival rate and quality of life of patients with heart failure. Artesunate (ART) is an artemisinin derivative, with good water solubility and higher oral bioavailability. The main aim of this study was to determine the role of ART in HT mice. METHODS: In animal experiments, mice were divided into the control group, HT group, low ART+HT group, and high ART+HT group. Next, inflammatory cell infiltration, oxidative stress injury, and myocardial cell apoptosis were determined in heart tissue. The proportion of multiple lymphocytes in spleen and lymph nodes was then determined using flow cytometry. In addition, cell experiments were conducted to determine the changes in expression of surface maturation markers of BMDC and changes in intracellular reactive oxygen species after LPS stimulation. Finally, western blot analysis was performed to determine the levels of endoplasmic reticulum stress-related proteins (CHOP/ATF4/PERK). RESULTS: The survival time of mice in the ART treatment group was significantly prolonged and was positively correlated with the dose. In animal experiments, ART significantly reduced inflammatory cell infiltration in heart tissue and the proportion of CD4+CD8+ T cells in spleens and lymph nodes. Moreover, ART treatment lowered the 8-OHdg in hearts and myocardial apoptosis. In cell experiments, ART treatment slowed down the development and maturation of BMDCs by inhibiting the expression of endoplasmic reticulum stress-related proteins. Furthermore, the treatment alleviated the oxidative stress damage of BMDCs. CONCLUSION: ART can inhibit maturation of dendritic cells through the endoplasmic reticulum stress signaling pathway, thereby alleviating acute rejection in mice after heart transplantation.
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Trasplante de Corazón , Calidad de Vida , Factor de Transcripción Activador 4/metabolismo , Factor de Transcripción Activador 4/farmacología , Animales , Apoptosis , Artesunato/farmacología , Artesunato/uso terapéutico , Células Dendríticas/metabolismo , Estrés del Retículo Endoplásmico , Humanos , Ratones , Transducción de Señal , eIF-2 Quinasa/metabolismo , eIF-2 Quinasa/farmacologíaRESUMEN
BACKGROUND: The aim of this study is to introduce a new method of percutaneous endoscopic decompression under 3D real-time image-guided navigation for spinal stenosis in degenerative kyphoscoliosis patients without instability or those who with multiple comorbidities. Decompression alone using endoscope for kyphoscoliosis patient is technical demanding and may result in unnecessary bone destruction leading to further instability. The O-arm/StealthStation system is popular for its ability to provide automated registration with intraoperative, postpositioning computed tomography (CT) which results in superior accuracy in spine surgery. METHODS: In this study, we presented four cases. All patients were over seventy years old female with variable degrees of kyphoscoliosis and multiple comorbidities who could not endure major spine fusion surgery. Percutaneous endoscopic unilateral laminotomy and bilateral decompression under 3D real-time image-guided navigation were successfully performed. Patients' demographics, image study parameters, and outcome measurements including pre- and post-operative serial Visual analog scale (VAS), and Oswestry Disability Index (ODI) were well documented. The follow-up time was 1 year. RESULTS: Pre- and post-operative MRI showed average dural sac cross sectional area (DSCSA) improved from 81.62 (range 67.34-89.07) to 153.27 (range 127.96-189.73). Preoperative neurological symptoms including radicular leg pain improved postoperatively. The mean ODI (%) were 85 (range 82.5-90) at initial visit, 35.875 (range 25-51) at 1 month post-operatively, 26.875 (range 22.5-35) at 6 months post-operatively and 22.5 (range 17.5-30) at 12 months post-operatively (p < 0.05). The mean VAS score were 9 (range 8-10) at initial visit, 2.25 (range 2-3) at 1 month post-operatively, 1.75 (range 1-2) at 6 months post-operatively and 0.25 (range 0-1) at 12 months post-operatively (p < 0.05). There was no surgery-related complication. CONCLUSIONS: To the best of our knowledge, this is the first preliminary study of percutaneous endoscopic laminotomy under O-arm navigation with successful outcomes. The innovative technique may serve as a promising solution in treating spinal stenosis patients with lumbar kyphoscoliosis and multiple comorbidities.
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Estenosis Espinal , Cirugía Asistida por Computador , Anciano , Descompresión Quirúrgica , Femenino , Humanos , Imagenología Tridimensional , Laminectomía , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Estenosis Espinal/complicaciones , Estenosis Espinal/diagnóstico por imagen , Estenosis Espinal/cirugía , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
PURPOSE: To determine the clinical effectiveness and long-term outcome of stent insertion for malignant superior vena cava (SVC) syndrome. MATERIALS AND METHODS: From June 2010 to April 2016, 47 patients with malignant SVC syndrome were treated with stent insertion in our center. Data regarding the technical success, clinical success, and long-term outcome were collected and analyzed retrospectively. RESULTS: SVC stent insertion was successfully performed in all patients. A total of 65 stents were used. No procedure-related complication occurred in these patients. The mean SVC pressure gradient decreased from 17.8 mmHg before stent insertion to 7.6 mmHg after stent insertion (P < 0.001). Clinical success was 100%. During a mean follow-up period of 6 months (range 10 days-13 months), 25 patients underwent subsequent anti-cancer treatment. Six patients (12.8%) experienced re-obstruction of stent 1 to 189 days (median 76 days) after stent insertion. All patients died during the follow-up. The median stent patency time and survival were 339 and 167 days, respectively. The cumulative 3-, 6-, and 12-month stent patency rates were 93.4, 87.4, and 81.2%, respectively. The cumulative 3-, 6-, and 12-month survival rates were 83, 38.3, and 2.1%, respectively. The independent predictors of prolonging survival after stent insertion were lower tumor stage (P = 0.018) and subsequent anti-cancer treatment after stent insertion (P = 0.009). CONCLUSION: Stent insertion is a simple, safe, and effective method for patients with malignant SVC syndrome. Subsequent anti-cancer treatment after stent insertion may increase the survival.
Asunto(s)
Cuidados Paliativos/métodos , Stents , Síndrome de la Vena Cava Superior/mortalidad , Síndrome de la Vena Cava Superior/patología , Síndrome de la Vena Cava Superior/cirugía , Neoplasias Vasculares/mortalidad , Neoplasias Vasculares/secundario , Neoplasias Vasculares/cirugía , Anciano , Femenino , Fluoroscopía , Humanos , Masculino , Persona de Mediana Edad , Radiografía Intervencional , Estudios RetrospectivosRESUMEN
Chondrosarcoma is the second most frequently occurring type of bone malignancy characterized by distant metastatic propensity. Vascular endothelial growth factor-C (VEGF-C) is the major lymphangiogenic factor, and makes crucial contributions to tumour lymphangiogenesis and lymphatic metastasis. Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes. In recent years, adiponectin has also been indicated as facilitating tumorigenesis, angiogenesis and metastasis. However, the effect of adiponectin on VEGF-C regulation and lymphangiogenesis in chondrosarcoma has remained largely a mystery. In the present study, we have shown a clinical correlation between adiponectin and VEGF-C, as well as tumour stage, in human chondrosarcoma tissues. We further demonstrated that adiponectin promoted VEGF-C expression and secretion in human chondrosarcoma cells. The conditioned medium from adiponectin-treated cells significantly induced tube formation and migration of human lymphatic endothelial cells. In addition, adiponectin knock down inhibited lymphangiogenesis in vitro and in vivo We also found that adiponectin-induced VEGF-C is mediated by the calmodulin-dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK) and p38 signaling pathway. Furthermore, the expression of miR-27b was negatively regulated by adiponectin via the CaMKII, AMPK and p38 cascade. The present study is the first to describe the mechanism of adiponectin-promoted lymphangiogenesis by up-regulating VEGF-C expression in chondrosarcomas. Thus, adiponectin could serve as a therapeutic target in chondrosarcoma metastasis and lymphangiogenesis.