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The perioculomotor (pIII) region of the midbrain was postulated as a sleep-regulating center in the 1890s but largely neglected in subsequent studies. Using activity-dependent labeling and gene expression profiling, we identified pIII neurons that promote non-rapid eye movement (NREM) sleep. Optrode recording showed that pIII glutamatergic neurons expressing calcitonin gene-related peptide alpha (CALCA) are NREM-sleep active; optogenetic and chemogenetic activation/inactivation showed that they strongly promote NREM sleep. Within the pIII region, CALCA neurons form reciprocal connections with another population of glutamatergic neurons that express the peptide cholecystokinin (CCK). Activation of CCK neurons also promoted NREM sleep. Both CALCA and CCK neurons project rostrally to the preoptic hypothalamus, whereas CALCA neurons also project caudally to the posterior ventromedial medulla. Activation of each projection increased NREM sleep. Together, these findings point to the pIII region as an excitatory sleep center where different subsets of glutamatergic neurons promote NREM sleep through both local reciprocal connections and long-range projections.
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Hipotálamo/metabolismo , Mesencéfalo/metabolismo , Neurônios/metabolismo , Fases do Sono/fisiologia , Animais , Colecistocinina/metabolismo , Hipotálamo/citologia , Mesencéfalo/citologia , Camundongos , Camundongos Transgênicos , Neurônios/citologia , OptogenéticaRESUMO
For nearly a century, evidence has accumulated indicating that the lateral hypothalamus (LH) contains neurons essential to sustain wakefulness. While lesion or inactivation of LH neurons produces a profound increase in sleep, stimulation of inhibitory LH neurons promotes wakefulness. To date, the primary wake-promoting cells that have been identified in the LH are the hypocretin/orexin (Hcrt) neurons, yet these neurons have little impact on total sleep or wake duration across the 24-h period. Recently, we and others have identified other LH populations that increase wakefulness. In the present study, we conducted microendoscopic calcium imaging in the LH concomitant with EEG and locomotor activity (LMA) recordings and found that a subset of LH neurons that express Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα) are preferentially active during wakefulness. Chemogenetic activation of these neurons induced sustained wakefulness and greatly increased LMA even in the absence of Hcrt signaling. Few LH CaMKIIα-expressing neurons are hypocretinergic or histaminergic while a small but significant proportion are GABAergic. Ablation of LH inhibitory neurons followed by activation of the remaining LH CaMKIIα neurons induced similar levels of wakefulness but blunted the LMA increase. Ablated animals showed no significant changes in sleep architecture but both spontaneous LMA and high theta (8 to 10 Hz) power during wakefulness were reduced. Together, these findings indicate the existence of two subpopulations of LH CaMKIIα neurons: an inhibitory population that promotes locomotion without affecting sleep architecture and an excitatory population that promotes prolonged wakefulness even in the absence of Hcrt signaling.
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Região Hipotalâmica Lateral , Vigília , Animais , Vigília/fisiologia , Região Hipotalâmica Lateral/fisiologia , Orexinas/metabolismo , Sono/fisiologia , Neurônios/metabolismo , Transdução de SinaisRESUMO
Modulation of histone methylation status is regarded as an important mechanism of epigenetic regulation and has substantial clinical potential for the therapy of diseases, including cancer and other disorders. The present study aimed to provide a comprehensive introduction to the enzymology of histone demethylases, as well as their cancerous roles, molecular mechanisms, therapeutic possibilities, and challenges for targeting them, in order to advance drug design for clinical therapy and highlight new insight into the mechanisms of these enzymes in cancer. A series of clinical trials have been performed to explore potential roles of histone demethylases in several cancer types. Numerous targeted inhibitors associated with immunotherapy, chemotherapy, radiotherapy, and targeted therapy have been used to exert anticancer functions. Future studies should evaluate the dynamic transformation of histone demethylases leading to carcinogenesis and explore individual therapy.
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Histona Desmetilases , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/enzimologia , Neoplasias/patologia , Neoplasias/tratamento farmacológico , Histona Desmetilases/metabolismo , Histona Desmetilases/antagonistas & inibidores , Animais , Epigênese Genética , Histonas/metabolismo , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologiaRESUMO
INTRODUCTION: When initial resection of rectal neuroendocrine tumors (r-NETs) is not R0, persistence of local residue could lead to disease recurrence. This study aimed to evaluate the interest of systematic resection of non-R0 r-NET scars. METHODS: Retrospective analysis of all the consecutive endoscopic revisions and resections of the scar after non-R0 resections of r-NETs. RESULTS: A total of 100 patients were included. Salvage endoscopic procedure using endoscopic submucosal dissection or endoscopic full-thickness resection showed an R0 rate of near 100%. Residual r-NET was found in 43% of cases. DISCUSSION: In case of non-R0 resected r-NET, systematic scar resection by endoscopic full-thickness resection or endoscopic submucosal dissection seems necessary.
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Ressecção Endoscópica de Mucosa , Tumores Neuroendócrinos , Neoplasias Retais , Humanos , Tumores Neuroendócrinos/cirurgia , Cicatriz/etiologia , Cicatriz/patologia , Estudos Retrospectivos , Resultado do Tratamento , Recidiva Local de Neoplasia/cirurgia , Neoplasias Retais/cirurgia , Neoplasias Retais/patologia , Ressecção Endoscópica de Mucosa/métodosRESUMO
Percutaneous coronary intervention is the main strategy of revascularization and has been shown to improve outcomes in some patients with ST-segment elevation myocardial infarction (STEMI). However, multivessel disease (MVD), a common condition in these patients, is associated with worse clinical outcomes compared to single-vessel disease. Despite intervention being a standard treatment for coronary artery disease, optimal strategies and timings for patients with STEMI and MVD remain unclear. Numerous studies and meta-analyses have investigated this topic; however, many current conclusions are based on observational studies. Furthermore, clinical guidelines regarding the management of patients with STEMI and MVD contain conflicting recommendations. Therefore, we aimed to compile relevant studies and newly available evidence-based medicines to explore the most effective approach.
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OBJECTIVES: To investigate if spatial recurrence pattern is associated with patient prognosis, and whether MRI vascular habitats can predict spatial pattern. METHODS: In this retrospective study, 69 patients with locally recurrent high-grade gliomas (HGGs) were included. The cohort was divided into intra-resection cavity recurrence (ICR) and extra-resection cavity recurrence (ECR) patterns, according to the distance between the location of the recurrent tumor and the resection cavity or surgical region. Four vascular habitats, high angiogenic tumor, low angiogenic tumor, infiltrated peripheral edema, and vasogenic peripheral edema, were segmented and vascular heterogeneity parameters were analyzed. The survival and diagnostic performance under different spatial recurrence patterns were analyzed by Kaplan-Meier and ROC. A nomogram model was constructed by regression analysis and validated by bootstrapping technique. RESULTS: Progression-free survival (PFS) and overall survival (OS) were longer for ICR (n = 32) than those for ECR (n = 37) (median PFS: 8 vs. 5 months, median OS: 17 vs. 13 months, p < 0.05). MRI vascular habitat analyses showed ECR had higher median relative cerebral blood volume (rCBVmedian) at each habitat than ICR (all p < 0.01). The rCBVmedian at IPE had good diagnostic performance (AUC: 0.727, 95%CI: 0.607, 0.828). The AUC of the nomogram based on MRI vascular habitats and clinical factors was 0.834 (95%CI: 0.726, 0.913) and was confirmed as 0.833 (95%CI: 0.830, 0.836) by bootstrapping validation. CONCLUSIONS: The spatial pattern of locally recurrent HGGs is associated with prognosis. MRI vascular heterogeneity parameter could be used as a non-invasive imaging marker to predict spatial recurrence pattern. CLINICAL RELEVANCE STATEMENT: Vascular heterogeneity parameters based on MRI vascular habitat analyses can non-invasively predict the spatial patterns of locally recurrent high-grade gliomas, providing a new diagnostic basis for clinicians to develop the extent of surgical resection and postoperative radiotherapy planning. KEY POINTS: ⢠Intra-resection cavity pattern was associated with longer progression-free survival and overall survival in locally recurrent high-grade gliomas. ⢠Higher vascular heterogeneities in extra-resection cavity recurrence than in intra-resection cavity recurrence and the vascular heterogeneity parameters had good diagnostic performance in discriminating spatial recurrence pattern. ⢠A nomogram model based on MRI vascular habitats and clinical factors had good performance in predicting spatial recurrence pattern.
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Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Estudos Retrospectivos , Glioma/diagnóstico por imagem , Glioma/cirurgia , Imageamento por Ressonância Magnética/métodos , EdemaRESUMO
BACKGROUND: Downregulated expression of cold-inducible RNA binding protein (CIRP), a stress-response protein, has been demonstrated in the hearts of patients with heart failure (HF). However, whether CIRP plays a critical role in the pathogenesis of HF remains unknown. Zr17-2 is a recently identified CIRP agonist, which can enhance the expression of CIRP in hearts. Herein, we evaluated the effects of zr17-2 on the development of HF in a rat model of myocardial infarction (MI). METHODS: Male SD rats were pretreated with CIRP agonist zr17-2 or vehicle saline for 6 consecutive days, followed by MI induction. 1-week post-MI, cardiac function, and structural and molecular changes were determined by echocardiography and molecular biology methods. RESULTS: Excitingly, we found that pretreatment with zr17-2 significantly attenuated MI-induced cardiac dysfunction and dilation, coupled with reduced infarction size and cardiac remodeling. In addition, increased inflammatory response in the peri-infarcted heart including macrophage infiltration and the expression of inflammatory genes were all significantly decreased by zr17-2 pretreatment, suggesting an anti-inflammatory effect of zr17-2. Moreover, zr17-2 pretreatment also upregulated the antioxidant genes (e.g. NQO-1, Nrf2, and HO-1) level in the hearts. In isolated cultured cardiomyocytes, pretreatment with zr17-2 markedly attenuated cell injury and apoptosis induced by oxidative injury, along with elevation of Nrf2-related antioxidant genes and CIRP. However, silencing CIRP abolished zr17-2's antioxidant effects against oxidative injury, confirming that zr17-2's role is dependent on CIRP. CONCLUSION: Collectively, our study suggests CIRP plays a crucial role in the development of HF and a beneficial effect of CIRP agonist in preventing MI-induced HF, possibly via anti-inflammatory and anti-oxidant pathways.
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Insuficiência Cardíaca , Infarto do Miocárdio , Animais , Humanos , Masculino , Ratos , Anti-Inflamatórios , Antioxidantes , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/prevenção & controle , Infarto do Miocárdio/complicações , Fator 2 Relacionado a NF-E2/metabolismo , Ratos Sprague-Dawley , Regulação para CimaRESUMO
BACKGROUND: Uveal melanoma (UVM) stands as the predominant type of primary intraocular malignancy among adults. The clinical significance of N7-methylguanosine (m7G), a prevalent RNA modifications, in UVM remains unclear. METHODS: Primary information from 80 UVM patients were analyzed as the training set, incorporating clinical information, mutation annotations and mRNA expression obtained from The Cancer Genome Atlas (TCGA) website. The validation set was carried out using Gene Expression Omnibus (GEO) database GSE22138 and GSE84976. Kaplan-Meier and Cox regression of univariate analyses were subjected to identify m7G-related regulators as prognostic genes. RESULT: A prognostic risk model comprising EIF4E2, NUDT16, SNUPN and WDR4 was established through Cox regression of LASSO. Evaluation of the model's predictability for UVM patients' prognosis by Receiver Operating Characteristic (ROC) curves in the training set, demonstrated excellent performance Area Under the Curve (AUC) > 0.75. The high-risk prognosis within the TCGA cohort exhibit a notable worse outcome. Additionally, an independent correlation between the risk score and overall survival (OS) among UVM patients were identified. External validation of this model was carried out using the validation sets (GSE22138 and GSE84976). Immune-related analysis revealed that patients with high score of m7G-related risk model exhibited elevated level of immune infiltration and immune checkpoint gene expression. CONCLUSION: We have developed a risk prediction model based on four m7G-related regulators, facilitating effective estimate UVM patients' survival by clinicians. Our findings shed novel light on essential role of m7G-related regulators in UVM and suggest potential novel targets for the diagnosis, prognosis and therapy of UVM.
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Guanosina , Melanoma , Neoplasias Uveais , Humanos , Neoplasias Uveais/genética , Neoplasias Uveais/mortalidade , Melanoma/genética , Prognóstico , Guanosina/análogos & derivados , Feminino , Masculino , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/genética , Curva ROC , Estimativa de Kaplan-MeierRESUMO
We put forward a novel method for producing ultrarelativistic high-density high-polarization positrons through a single-shot interaction of a strong laser with a tilted solid foil. In our method, the driving laser ionizes the target, and the emitted electrons are accelerated and subsequently generate abundant γ photons via the nonlinear Compton scattering, dominated by the laser. These γ photons then generate polarized positrons via the nonlinear Breit-Wheeler process, dominated by a strong self-generated quasistatic magnetic field B^{S}. We find that placing the foil at an appropriate angle can result in a directional orientation of B^{S}, thereby polarizing positrons. Manipulating the laser polarization direction can control the angle between the γ photon polarization and B^{S}, significantly enhancing the positron polarization degree. Our spin-resolved quantum electrodynamics particle-in-cell simulations demonstrate that employing a laser with a peak intensity of about 10^{23} W/cm^{2} can obtain dense (â³10^{18} cm^{-3}) polarized positrons with an average polarization degree of about 70% and a yield of above 0.1 nC per shot. Moreover, our method is feasible using currently available or upcoming laser facilities and robust with respect to the laser and target parameters. Such high-density high-polarization positrons hold great significance in laboratory astrophysics, high-energy physics, and new physics beyond the standard model.
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Molybdenum disulfide (MoS2) has been deemed as one of the promising noble-metal-free electrocatalysts for hydrogen evolution reaction (HER), but it suffers from the inert basal plane and low electronic conductivity. Regulating the morphology of MoS2during the synthesis on conductive substrates is a synergistic strategy for enhancing the HER performance. In this work, vertical MoS2nanosheets were fabricated on carbon cloth (CC) using an atmospheric pressure chemical vapor deposition method. The growth process could be effectively tuned through introducing hydrogen gas during vapor deposition process, resulting in nanosheets with increased edge density. The mechanism for edge-enriching through controlling the growth atmosphere is systematically studied. The as-prepared MoS2exhibits excellent HER activity due to the combination of optimized microstructures and coupling with CC. Our findings provide new insights to design advanced MoS2-based electrocatalysts for HER.
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BACKGROUND: Diabetic cardiomyopathy (DCM) pathogenesis is a common complication of diabetes, but effective treatments remain limited. Mitochondrial-derived peptide MOTS-c has shown therapeutic promise in animal models of various heart diseases, but its efficacy in DCM is unknown. This study investigates the effects of MOTS-c treatment in a mouse model of type 1 diabetes-induced DCM. METHODS: Type 1 diabetes (T1DM) was induced in mice by streptozotocin (STZ) injection. After diabetes establishment, the mice were randomly dividend into two groups treated with or without MOTS-c peptide, which was administered subcutaneously by osmotic pump for 12 weeks. At the end of the experiment, cardiac function, histology, and molecular changes were determined. RESULTS: The results showed that diabetic mice exhibited significant cardiac dysfunction, dilatation, and adverse cardiac remodeling. MOTS-c treatment markedly ameliorated these diabetes-associated myocardial function and structure abnormalities. Additionally, MOTS-c reversed AMPK signaling deactivation and inhibited inflammation in the diabetic heart. CONCLUSIONS: Our data demonstrated a protective effect of MOTS-c against diabetic cardiomyopathy potentially by activating the AMPK pathway and inhibiting inflammation. These findings demonstrate the therapeutic efficacy of MOTS-c for diabetic cardiomyopathy and warrant further investigation into its clinical potential.
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In humans and other mammalian species, lesions in the preoptic area of the hypothalamus cause profound sleep impairment, indicating a crucial role of the preoptic area in sleep generation. However, the underlying circuit mechanism remains poorly understood. Electrophysiological recordings and c-Fos immunohistochemistry have shown the existence of sleep-active neurons in the preoptic area, especially in the ventrolateral preoptic area and median preoptic nucleus. Pharmacogenetic activation of c-Fos-labelled sleep-active neurons has been shown to induce sleep. However, the sleep-active neurons are spatially intermingled with wake-active neurons, making it difficult to target the sleep neurons specifically for circuit analysis. Here we identify a population of preoptic area sleep neurons on the basis of their projection target and discover their molecular markers. Using a lentivirus expressing channelrhodopsin-2 or a light-activated chloride channel for retrograde labelling, bidirectional optogenetic manipulation, and optrode recording, we show that the preoptic area GABAergic neurons projecting to the tuberomammillary nucleus are both sleep active and sleep promoting. Furthermore, translating ribosome affinity purification and single-cell RNA sequencing identify candidate markers for these neurons, and optogenetic and pharmacogenetic manipulations demonstrate that several peptide markers (cholecystokinin, corticotropin-releasing hormone, and tachykinin 1) label sleep-promoting neurons. Together, these findings provide easy genetic access to sleep-promoting preoptic area neurons and a valuable entry point for dissecting the sleep control circuit.
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Técnicas de Rastreamento Neuroanatômico , Neurônios/fisiologia , Área Pré-Óptica/citologia , Área Pré-Óptica/fisiologia , Sono/fisiologia , Transcriptoma , Animais , Biomarcadores/análise , Channelrhodopsins , Canais de Cloreto/metabolismo , Canais de Cloreto/efeitos da radiação , Colecistocinina/análise , Colecistocinina/genética , Hormônio Liberador da Corticotropina/análise , Hormônio Liberador da Corticotropina/genética , Feminino , Neurônios GABAérgicos/metabolismo , Neurônios GABAérgicos/efeitos da radiação , Região Hipotalâmica Lateral/fisiologia , Masculino , Camundongos , Neurônios/efeitos dos fármacos , Neurônios/efeitos da radiação , Optogenética , Área Pré-Óptica/efeitos dos fármacos , Área Pré-Óptica/efeitos da radiação , Proteínas Proto-Oncogênicas c-fos/análise , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ribossomos/metabolismo , Análise de Sequência de RNA , Análise de Célula Única , Sono/efeitos dos fármacos , Sono/efeitos da radiação , Taquicininas/análise , Taquicininas/genética , Vigília/fisiologia , Vigília/efeitos da radiaçãoRESUMO
Artificial groundwater recharge with reclaimed water (secondary effluent from wastewater treatment plants) has become an important approach to solving water scarcity worldwide. Microorganisms in activated sludge can secrete many extracellular polymeric substances (EPS). However, information on the impact of EPS on the movement of heavy metals in porous media and their environmental effects on underground networks is limited. To assess this risk, we extracted EPS from the aerobic section of a wastewater treatment plant using hot sodium hydroxide and conducted experiments using one-dimensional sand columns to investigate how ion composition and strength affect the movement and interaction of cadmium (Cd) and EPS in porous media. The results showed that EPS facilitated Cd migration in porous media. Sodium (Na) and calcium (Ca) ions promoted the migration of Cd in porous media and EPS-Cd complexation. The effect of Ca was more significant than that of Na. As the Na adsorption ratio increased, the migration ability of Cd in porous media and the complexation ability of EPS with Cd decreased. Therefore, when estimating the migration of EPS and Cd in subsurface environments, careful consideration should be given to prevent the risk of groundwater pollution.
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Cádmio , Esgotos , Matriz Extracelular de Substâncias Poliméricas , Areia , Concentração Osmolar , SódioRESUMO
Spinal cord injury without radiographic abnormality (SCIWORA) is a term that denotes clinical symptoms of traumatic myelopathy without radiographic or computed tomographic features of vertebral fracture or instability. However, SCIWORA in adults is very rare, especially that involving the thoracic spine. We describe the case of a 38-year-old man who complained of weakness in the right lower extremity for two hours. The injury occurred due to rapid spinal cord rotation-stretching. The patient was diagnosed with SCIWORA at the T4 level, manifesting as Brown-Sequard syndrome (BBS). Finally, he was able to walk independently without assistance after two-month treatment. SCIWORA due to spinal cord rotation-stretching injury, manifesting as BSS, is a very rare mechanism of injury. When X-ray and CT scans rule out the diagnosis of spinal fractures, SCIWORA should be suspected. We recommend that clinicians should have a comprehensive and systematic understanding of this disease to greatly reduce misdiagnosis and improve the level of treatment.
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Síndrome de Brown-Séquard , Traumatismos da Medula Espinal , Fraturas da Coluna Vertebral , Adulto , Masculino , Humanos , Síndrome de Brown-Séquard/diagnóstico por imagem , Síndrome de Brown-Séquard/etiologia , Rotação , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico por imagem , Perna (Membro)RESUMO
Cold-inducible RNA-binding protein (CIRP) is a stress-response protein that is expressed in various types of cells and acts as an RNA chaperone, modifying the stability of its targeted mRNA. Intracellular CIRP could also be released into extracellular space and once released, extracellular CIRP (eCIRP) acts as a damage-associated molecular pattern (DAMP) to induce and amplify inflammation. Recent studies have found that eCIRP could promote acute lung injury (ALI) via activation of macrophages, neutrophils, pneumocytes and lung vascular endothelial cells in context of sepsis, haemorrhagic shock, intestinal ischemia/reperfusion injury and severe acute pancreatitis. In addition, CIRP is also highly expressed in the bronchial epithelial cells and its expression is upregulated in the bronchial epithelial cells of patients with chronic obstructive pulmonary diseases (COPD) and rat models with chronic bronchitis. CIRP is a key contributing factor in the cold-induced exacerbation of COPD by promoting the expression of inflammatory genes and hypersecretion of airway mucus in the bronchial epithelial cells. Besides, CIRP is also involved in regulating pulmonary fibrosis, as eCIRP could directly activate and induce an inflammatory phenotype in pulmonary fibroblast. This review summarizes the findings of CIRP investigation in respiratory diseases and the underlying molecular mechanisms.
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Células Endoteliais , Pneumopatias/metabolismo , Proteínas de Ligação a RNA/metabolismo , Doença Aguda , Animais , Células Endoteliais/metabolismo , Humanos , Pulmão/metabolismo , Pancreatite , RatosRESUMO
MOTS-c, a mitochondrial-derived peptide (MDP), has been shown to have multiple biological activities such as antioxidation, anti-inflammation, and anti-apoptosis properties. In the present study, we aimed at evaluating the therapeutic effect of MOTS-c peptide in an animal model of heart failure. The heart failure mouse model was made by transverse aortic constriction (TAC) operations. The MOTS-c peptide was administrated subcutaneously by using an osmotic pump. At the end of the animal experiment, cardiac function was evaluated by echocardiography, and heart tissues were subjected to histological and molecular analysis. In vitro cultured H9C2 cells were used to test the effects of MOTS-c overexpression on cell death in response to H2 O2 stimulation. Our study showed that MOTS-c peptide attenuated TAC-induced cardiac dysfunction and remodelling. In addition, the MOTS-c peptide reduced the inflammatory response and upregulated the antioxidant capacity, coupled with the activation of the AMPK pathway in the heart of the TAC mouse model. In in vitro cultured cardiac cells, overexpression of MOTS-c was shown to activate the AMPK pathway and protect cell apoptosis in response to H2 O2 stimulation. Taken together, our study suggested that MOTS-c peptides may have therapeutic potential in treating HF.
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Proteínas Quinases Ativadas por AMP , Insuficiência Cardíaca , Camundongos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Peptídeo C , Insuficiência Cardíaca/metabolismo , Coração , Modelos Animais de Doenças , Antioxidantes , Peptídeos/farmacologia , Camundongos Endogâmicos C57BLRESUMO
Structural transformations and lattice expansion of oleate-capped iron oxide nanocube superlattices are studied by time-resolved small-angle X-ray scattering (SAXS) during solvent removal. The combination of conductor-like screening model for real solvents (COSMO-RS) theory with computational fluid dynamics (CFD) modeling provides information on the solvent composition and polarity during droplet evaporation. Evaporation-driven poor-solvent enrichment in the presence of free oleic acid results in the formation of superlattices with a tilted face-centered cubic (fcc) structure when the polarity reaches its maximum. The tilted fcc lattice expands subsequently during the removal of the poor solvent and eventually transforms to a regular simple cubic (sc) lattice during the final evaporation stage when only free oleic acid remains. Comparative studies show that both the increase in polarity as the poor solvent is enriched and the presence of a sufficient amount of added oleic acid is required to promote the formation of structurally diverse superlattices with large domain sizes.
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Ácido Oleico , Tensoativos , Espalhamento a Baixo Ângulo , Solventes/química , Difração de Raios XRESUMO
Objectives: This meta-analysis was to verify the short-time efficacy and safety of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Background: Abciximab has long-term efficacy in patients with STEMI undergoing PCI, but the short-term efficacy is still controversial. Methods: We conducted a systematic review and meta-analysis compared with or without abciximab in patients with STEMI undergoing PCI. The relevant randomized controlled trials were included by searching PubMed, EMBASE, Cochrane Library, and Web of Science databases and other sources. The relative risk (RR) and 95% confidence intervals (CI) of outcomes were calculated by the fixed-effects model. Results: Ten randomized controlled trials with 5008 patients met inclusion criteria. There were no significant differences in risk of all-cause death at 30-day (RR 0.79, CI 0.55-1.12, P=0.18), major bleeding (1.37, 0.93-2.03, P=0.11), and transfusion (1.23, 0.94-1.61, P=0.13) between the two groups. However, there were significant differences in risk of all-cause death at 6 months (0.57, 0.36-0.90, P=0.02), recurrent myocardial infarction (0.55, 0.33-0.92, P=0.02), repeat revascularization (0.58, 0.43-0.78, P=0.0004), final TIMI flow <3 (0.77, 0.62-0.96, P=0.02), minor bleeding (1.29, 1.02-1.63, P=0.04), and thrombocytopenia (2.04, 1.40-2.97, P=0.0002). Conclusions: The application of abciximab can lead to a lower risk of reinfarction, revascularization, and all-cause death at 6 months, but a higher risk of minor bleeding, and thrombocytopenia.
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Abciximab , Infarto do Miocárdio , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Abciximab/efeitos adversos , Abciximab/uso terapêutico , Hemorragia/induzido quimicamente , Humanos , Infarto do Miocárdio/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
ABSTRACT: The risk of bleeding is high in East Asians, whether East Asian patients with acute coronary syndrome choose ticagrelor or clopidogrel is still controversial. In this study, PubMed, EMBASE, Cochrane Library database, and other sources were systematically searched. The primary efficacy outcome was all-cause death, the primary safety outcomes were any bleeding, PLATO major bleeding, and fatal bleeding. The secondary outcomes included vascular-cause death, myocardial infarction, stent thrombosis, stroke, and dyspnea. A total of 8 randomized controlled trials with 3597 patients met inclusion criteria. Compared with clopidogrel, ticagrelor had significantly higher incidence of any bleeding [risk ratio (RR), 1.63; 1.33-1.99; P < 0.00001], PLATO major bleeding (RR 1.56; 1.15-2.12; P = 0.004), and dyspnea (RR 2.60; 1.68-4.00; P < 0.00001). However, ticagrelor was associated with a significantly reduced risk of stent thrombosis (RR 0.42; 0.19-0.92; P = 0.03). There was no significant difference in the risk of all-cause death (RR 0.87; 0.64-1.24; P = 0.44), fatal bleeding (RR 2.49; 0.79-7.86; P = 0.12), vascular-cause death (RR 0.88; 1.60-0.30; P = 0.52), myocardial infarction (RR 0.89; 0.65-1.23; P = 0.49), and stroke (RR 0.84; 0.47-1.50; P = 0.56) between the 2 groups. The present findings demonstrated that ticagrelor was associated with a higher risk of any bleeding, PLATO major bleeding, and dyspnea compared with clopidogrel in East Asian patients with acute coronary syndrome. However, it significantly reduced the risk of stent thrombosis. (Registered by PROSPERO, CRD42021255215).
Assuntos
Síndrome Coronariana Aguda , Infarto do Miocárdio , Intervenção Coronária Percutânea , Acidente Vascular Cerebral , Trombose , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Povo Asiático , Clopidogrel/efeitos adversos , Dispneia/diagnóstico , Dispneia/tratamento farmacológico , Dispneia/epidemiologia , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Humanos , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/epidemiologia , Intervenção Coronária Percutânea/efeitos adversos , Inibidores da Agregação Plaquetária/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle , Trombose/tratamento farmacológico , Ticagrelor/efeitos adversos , Resultado do TratamentoRESUMO
ABSTRACT: The purpose of this meta-analysis was to evaluate the efficacy and safety of proton pump inhibitors (PPIs) plus antithrombotic strategy in patients with coronary artery diseases compared with antithrombotic strategy alone. We searched PubMed, EMBASE, Cochrane Library, and Chinese Biomedical Medical Literature databases to retrieve randomized controlled trials investigating PPIs combined with antithrombotic strategy in coronary artery diseases. The primary efficacy outcome was major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety outcome was gastrointestinal events. Secondary outcomes included all-cause death, cardiovascular death, myocardial infarction, stent thrombosis, significant bleeding from gastroduodenal lesions, and gastroduodenal ulcer. Overall, 43,943 patients were enrolled from 19 trials. The incidence of MACCE [relative risk (RR) 1.05; 95% confidence interval (CI) 0.96-1.15], all-cause death (RR 0.84; 95% CI 0.69-1.01), cardiovascular death (RR 0.88; 95% CI 0.69-1.12), myocardial infarction (RR 0.98; 95% CI 0.88-1.09), stent thrombosis (RR 1.01; 95% CI 0.76-1.34), and gastroduodenal ulcer (RR 0.40; 95% CI 0.13-1.29) did not increase significantly in patients receiving PPIs compared with patients without those. There were significant differences in the risk of gastrointestinal events (RR 0.34; 95% CI 0.21-0.54) and significant bleeding from gastroduodenal lesions (RR 0.09; 95% CI 0.03-0.28) between the 2 groups. In patients with coronary artery diseases, PPIs plus antithrombotic strategy could reduce the risk of gastrointestinal events and significant bleeding from gastroduodenal lesions but may not affect the incidence of MACCE, all-cause death, cardiovascular death, myocardial infarction, stent thrombosis, and gastroduodenal ulcer (PROSPERO: CRD42021277899, date of registration October 10, 2021).