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OBJECTIVES: To investigate the incidence rate, clinical characteristics, and prognosis of neonatal stroke in Shenzhen, China. METHODS: Led by Shenzhen Children's Hospital, the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022. The incidence, clinical characteristics, treatment, and prognosis of neonatal stroke in Shenzhen were analyzed. RESULTS: The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137, 1/6 060, and 1/7 704, respectively. Ischemic stroke accounted for 75% (27/36); boys accounted for 64% (23/36). Among the 36 neonates, 31 (86%) had disease onset within 3 days after birth, and 19 (53%) had convulsion as the initial presentation. Cerebral MRI showed that 22 neonates (61%) had left cerebral infarction and 13 (36%) had basal ganglia infarction. Magnetic resonance angiography was performed for 12 neonates, among whom 9 (75%) had involvement of the middle cerebral artery. Electroencephalography was performed for 29 neonates, with sharp waves in 21 neonates (72%) and seizures in 10 neonates (34%). Symptomatic/supportive treatment varied across different hospitals. Neonatal Behavioral Neurological Assessment was performed for 12 neonates (33%, 12/36), with a mean score of (32±4) points. The prognosis of 27 neonates was followed up to around 12 months of age, with 44% (12/27) of the neonates having a good prognosis. CONCLUSIONS: Ischemic stroke is the main type of neonatal stroke, often with convulsions as the initial presentation, involvement of the middle cerebral artery, sharp waves on electroencephalography, and a relatively low neurodevelopment score. Symptomatic/supportive treatment is the main treatment method, and some neonates tend to have a poor prognosis.
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Acidente Vascular Cerebral , Humanos , Masculino , Recém-Nascido , Feminino , China/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Prognóstico , Eletroencefalografia , Incidência , Imageamento por Ressonância MagnéticaRESUMO
The drug efflux transporter permeability glycoprotein (P-gp) plays an important role in oral drug absorption and distribution. Under microgravity (MG), the changes in P-gp efflux function may alter the efficacy of oral drugs or lead to unexpected effects. Oral drugs are currently used to protect and treat multisystem physiological damage caused by MG; whether P-gp efflux function changes under MG remains unclear. This study aimed to investigate the alteration of P-gp efflux function, expression, and potential signaling pathway in rats and cells under different simulated MG (SMG) duration. The altered P-gp efflux function was verified by the in vivo intestinal perfusion and the brain distribution of P-gp substrate drugs. Results showed that the efflux function of P-gp was inhibited in the 7 and 21 day SMG-treated rat intestine and brain and 72 h SMG-treated human colon adenocarcinoma cells and human cerebral microvascular endothelial cells. P-gp protein and gene expression levels were continually down-regulated in rat intestine and up-regulated in rat brain by SMG. P-gp expression was regulated by the Wnt/ß-catenin signaling pathway under SMG, verified by a pathway-specific agonist and inhibitor. The elevated intestinal absorption and brain distribution of acetaminophen levels also confirmed the inhibited P-gp efflux function in rat intestine and brain under SMG. This study revealed that SMG alters the efflux function of P-gp and regulates the Wnt/ß-catenin signaling pathway in the intestine and the brain. These findings may be helpful in guiding the use of P-gp substrate drugs during spaceflight.
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Adenocarcinoma , Neoplasias do Colo , Ausência de Peso , Ratos , Humanos , Animais , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Via de Sinalização Wnt , Células Endoteliais/metabolismo , Intestinos , Encéfalo/metabolismoRESUMO
Carbon capture and storage (CCS) and carbon capture and utilization (CCU) are two kinds of strategies to reduce the CO2 concentration in the atmosphere, which is emitted from the burning of fossil fuels and leads to the greenhouse effect. With the unique properties of ionic liquids (ILs), such as low vapor pressures, tunable structures, high solubilities, and high thermal and chemical stabilities, they could be used as solvents and catalysts for CO2 capture and conversion into value-added chemicals. In this critical review, we mainly focus our attention on the tuning IL-based catalysts for CO2 conversion into quinazoline-2,4(1H,3H)-diones from o-aminobenzonitriles during this decade (2012~2022). Due to the importance of basicity and nucleophilicity of catalysts, kinds of ILs with basic anions such as [OH], carboxylates, aprotic heterocyclic anions, etc., for conversion CO2 and o-aminobenzonitriles into quinazoline-2,4(1H,3H)-diones via different catalytic mechanisms, including amino preferential activation, CO2 preferential activation, and simultaneous amino and CO2 activation, are investigated systematically. Finally, future directions and prospects for CO2 conversion by IL-based catalysts are outlined. This review is benefit for academic researchers to obtain an overall understanding of the synthesis of quinazoline-2,4(1H,3H)-diones from CO2 and o-aminobenzonitriles by IL-based catalysts. This work will also open a door to develop novel IL-based catalysts for the conversion of other acid gases such as SO2 and H2S.
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BACKGROUND: The association between serum erythrocyte immune function indexes and blue light treatment effect and severity in child patients with pathological jaundice was testified. METHODS: One hundred and seven children with pathological jaundice and 69 children with physiological jaundice were enrolled to analyze the association between erythrocyte immune function indexes and blue light treatment or disease progression. RESULTS: The area under the ROC curve (AUC) of red blood cell immune complex rosettes (RBC-ICR) and red blood cell C3b receptor rosette (RBC-C3bR) in diagnosing pathological jaundice and assessing the efficacy of blue light therapy overweighed 0.8. Meanwhile, the RBC-ICR values of the child patients were positively correlated with the severity of the disease, and the RBC-C3bR and red blood cell immune affinity receptor (FEER) values were negatively correlated with them (p < 0.05). CONCLUSIONS: The erythrocyte immune function indexes of child patients with pathological jaundice were relevant to the disease severity, and was provided with diagnostic value for pathological jaundice or assessed value for the efficacy of blue light therapy.
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Complexo Antígeno-Anticorpo , Icterícia , Criança , Eritrócitos , Humanos , Imunidade , Icterícia/diagnóstico , Icterícia/terapia , Formação de RosetaRESUMO
BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of neonatal death and permanent neurological disability. Here, we designed to quest therapeutic effects of diazoxide (DZ) on HIE and its mechanism. METHODS: The cell model of HIE was established. CCK8 and flow cytometry were applied to test cell viability and apoptosis. RT-qPCR and western blotting was evaluated to the expression of miR-21, PDCD4, PI3K, and p-AKT/AKT. Commercial kits were employed to detect SOD, MDA, LDH. DCFH-DA was used to measure intracellular ROS. ELISA was performed to estimate IL-1ß, IL-6 and TNF-α. Dual-luciferase reporter gene and RIP assay were applied to confirm the binding relationships between miR-21 and PDCD4. RESULTS: In H19-7 cells and PC12 cells stimulated by OGD, with low cell viability, high apoptosis, miR-21 high expression and PDCD4 low expression. However, the functions were all reversed by DZ administration. Furthermore, miR-21 inhibitor could abolish the beneficial effects of DZ on OGD-induced cells. Besides, miR-21 could interact with PDCD4. In addition, PDCD4 involved with the regulation of DZ to OGD-induced cells via PI3K/AKT pathway. CONCLUSION: DZ enhanced miR-21 level and inhibited PDCD4 level via PI3K/AKT pathway to resisted HIE.
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Hipóxia-Isquemia Encefálica , MicroRNAs , Animais , Apoptose , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Diazóxido/farmacologia , Diazóxido/uso terapêutico , Humanos , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Recém-Nascido , Isquemia , MicroRNAs/genética , MicroRNAs/metabolismo , Neuroproteção , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , RatosRESUMO
The preparation of highly active supported noble metal catalysts with a low noble metal loading has always been the ultimate goal of researchers working on catalysis. Hydrothermally treated Pt/Al2O3 (Pt/Al2O3-H) exhibits better catalytic activity than that (Pt/Al2O3-C) treated via the conventional calcination approach. At the high space velocity of 100,000 mL/(gâhr), the temperature that correspond to 50% toluene conversion (T50) of Pt/Al2O3-H is 115°C lower than that of Pt/Al2O3-C, and the turnover frequency (TOF) value can reach 0.0756 sec-1. The mechanism by which the hydrothermal approach enhances Pt/Al2O3 activity has been investigated. The structure associated with the high catalytic activity of Pt nanoparticles (NPs) can be retained via hydrothermal treatment. Furthermore, the support is transformed to AlO(OH) with numerous surface hydroxyl groups, which in turn can facilitate the adsorption of toluene. And the synergistic effects of Pt NPs and AlO(OH) increases the contents of Pt in oxidation state and active oxygen, which are beneficial for toluene oxidation.
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Tolueno , Adsorção , Catálise , Oxirredução , Tolueno/químicaRESUMO
Dragon's Blood is a red resin from Dracaena cochinchinensis (Lour.) S.C. Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has shown protective effects on intestinal disorders. Microgravity could alter intestinal homeostasis. However, the potential herbal drugs for preventing intestine epithelial barrier (IEB) dysfunction under microgravity are not available. This study aimed to investigate the effects of Dragon's Blood (DB) on microgravity-induced IEB injury and explore its underlying mechanism. A rat tail-suspension model was used to simulate microgravity (SMG). Histomorphology, ultrastructure, permeability, and expression of junction proteins in jejunum, ileum, and colon of SMG rats were determined. Proteomic analysis was used to identify differentially expressed proteins (DEPs) in rat ileum mucosa altered by DB. The potential mechanism of DB to protect IEB dysfunction was validated by western blotting. The effects of several components in DB were evaluated in SMG-treated Caco-2 cells. DB protected against IEB disruption by repairing microvilli and crypts, inhibiting inflammatory factors, lowering the permeability and upregulating the expression of tight and adherens junction proteins in the ileum of SMG rats. Proteomic analysis showed that DB regulated 1080 DEPs in rat ileum mucosa. DEPs were significantly annotated in cell-cell adhesion, focal adhesion, and cytoskeleton regulation. DB increased the expression of Rac1-WAVE2-Arp2/3 pathway proteins and F-actin to G-actin ratio, which promoted the formation of focal adhesions. Loureirin C in DB showed a protective effect on epithelial barrier injury in SMG-treated Caco-2 cells. DB could protect against IEB dysfunction induced by SMG, and its mechanism is associated with the formation of focal adhesions mediated by the Rac1-WAVE2-Arp2/3 pathway, which benefits intestinal epithelial cell migration and barrier repair.
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Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Mucosa Intestinal/metabolismo , Extratos Vegetais/farmacologia , Transdução de Sinais/efeitos dos fármacos , Simulação de Ausência de Peso/efeitos adversos , Família de Proteínas da Síndrome de Wiskott-Aldrich/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Animais , Células CACO-2 , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Humanos , Mucosa Intestinal/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The blood-brain barrier (BBB) is critical to maintaining central nervous system (CNS) homeostasis. However, the effects of microgravity (MG) on the BBB remain unclear. This study aimed to investigate the influence of simulated MG (SMG) on the BBB and explore its potential mechanism using a proteomic approach. Rats were tail-suspended to simulate MG for 21 days. SMG could disrupt the BBB, including increased oxidative stress levels, proinflammatory cytokine levels, and permeability, damaged BBB ultrastructure, and downregulated tight junctions (TJs) and adherens junctions (AJs) protein expression in the rat brain. A total of 554 differentially expressed proteins (DEPs) induced by SMG were determined based on the label-free quantitative proteomic strategy. The bioinformatics analysis suggested that DEPs were mainly enriched in regulating the cell-cell junction and cell-extracellular matrix biological pathways. The inhibited Ras-related C3 botulinum toxin substrate 1 (Rac1)/Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 (Wave2)/actin-related protein 3 (Arp3) pathway and the decreased ratio of filamentous actin (F-actin) to globular actin contributed to BBB dysfunction induced by SMG. In the human brain microvascular endothelial cell (HBMECs), SMG increased the oxidative stress levels and proinflammatory cytokine levels, promoted apoptosis, and arrested the cell cycle phase. Expression of TJs and AJs proteins were downregulated and the distribution of F-actin was altered in SMG-treated HBMECs. The key role of the Rac1/Wave2/Arp3 pathway in BBB dysfunction was confirmed in HBMECs with a specific Rac1 agonist. This study demonstrated that SMG induced BBB dysfunction and revealed that Rac1/Wave2/Arp3 could be a potential signaling pathway responsible for BBB disruption under SMG. These results might shed a novel light on maintaining astronaut CNS homeostasis during space travel.
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Proteína 3 Relacionada a Actina/metabolismo , Barreira Hematoencefálica/patologia , Regulação da Expressão Gênica , Proteoma/metabolismo , Simulação de Ausência de Peso/efeitos adversos , Família de Proteínas da Síndrome de Wiskott-Aldrich/metabolismo , Proteínas rac1 de Ligação ao GTP/metabolismo , Citoesqueleto de Actina , Animais , Barreira Hematoencefálica/metabolismo , Masculino , Proteoma/análise , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Junções ÍntimasRESUMO
The present study aimed to investigate the change of intestinal mucosa proteins, especially the alteration of intestinal drug metabolizing enzymes (IDMEs) following 14-day simulated microgravity. Morey-Holton tail-suspension analog was used to simulate microgravity. Intestinal mucosa proteins of rats were determined by label-free quantitative proteomic strategy. A total of 335 differentially expressed proteins (DEPs) were identified, 190 DEPs were upregulated, and 145 DEPs were downregulated. According to bioinformatic analysis, most of DEPs exhibited hydrolase, oxidoreductase, transferase, ligase, or lyase catalytic activity. DEPs were mainly enriched in metabolic pathways, including metabolism of amino acid, glucose, and carbon. Moreover, 11 of DEPs were involved in exogenous drug and xenobiotics metabolism. Owing to the importance of IDMEs for the efficacy and safety of oral drugs, the expression of cytochrome P450 1A2 (CYP1A2), CYP2D1, CYP3A2, CYP2E1, alcohol dehydrogenase 1 (ADH1), and glutathione S-transferase mu 5 (GSTM5) in rat intestine mucosa was determined by Western-blot. The activity of ADH, aldehyde dehydrogenase (ALDH) and GST was evaluated. Compared with control rats, the expression of CYP1A2, CYP2D1, CYP3A2, and ADH1 in the simulated microgravity (SMG) group of rats were dramatically decreased by 33.16%, 21.93%, 48.49%, and 22.83%, respectively. GSTM5 was significantly upregulated by 53.14% and CYP2E1 expression did not show a dramatical change in SMG group rats. Moreover, 14-day SMG reduced ADH activity, while ALDH and GST activities was not altered remarkably. It could be concluded that SMG dramatically affected the expression and activity of some IDMEs, which might alter the efficacy or safety of their substrate drugs under microgravity. The present study provided some preliminary information on IDMEs under microgravity. It revealed the potential effect of SMG on intestinal metabolism, which may be helpful to understand the intestinal health of astronauts and medication use.
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Álcool Desidrogenase/biossíntese , Sistema Enzimático do Citocromo P-450/biossíntese , Glutationa Transferase/biossíntese , Mucosa Intestinal/enzimologia , Proteômica , Simulação de Ausência de Peso , Animais , Regulação Enzimológica da Expressão Gênica , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
The long non-coding RNA (lncRNA) prostate cancer-associated ncRNA transcript 1 (PCAT-1) has been shown to promote prostate cancer cell proliferation through c-Myc and is associated with the poor prognosis of CRC patients. In the current study, it was hypothesized that the effect of PCAT-1 on the aggressiveness of CRC cells was dependent on the function of c-Myc. Human CRC cell lines Caco-2 and HT-29 were transfected with specific PCAT-1 shRNAs, and cell migration, invasiveness, and resistance to 5-fluorouracil were measured. To elucidate the role of c-Myc in PCAT-1 function, c-Myc was overexpressed in PCAT-1-silenced CRC cells and the effect of c-Myc overexpression on the aggressiveness of PCAT-1-silenced cells was detected. The results showed that knockdown of PCAT-1 in CRC cells suppressed cell motility and invasiveness, and sensitized the cells to 5-fluorouracil, as evidenced by the reduced viability and induced apoptosis in PCAT-1-silenced cells compared to the parental cells in response to 5-fluorouracil treatment. The expression of c-Myc in PCAT-1-silenced CRC cells was down-regulated, and forced expression of c-Myc partially restored the invasiveness in PCAT-1-silenced cells. In summary, the findings outlined in the current study suggest that PCAT-1 regulates the invasiveness and drug resistance in CRC cells and that PCAT-1 may promote CRC cell invasion by modulating the expression of c-Myc.
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Neoplasias Colorretais/metabolismo , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Proteínas Proto-Oncogênicas c-myc/biossíntese , RNA Neoplásico/metabolismo , Células CACO-2 , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Técnicas de Silenciamento de Genes , Humanos , Invasividade Neoplásica , Proteínas Proto-Oncogênicas c-myc/genética , RNA Longo não Codificante , RNA Neoplásico/genéticaRESUMO
BACKGROUND: The thought of producing offspring has rooted in Chinese culture after thousands of years of feudal society. Infertility in men would bear significant psychological distress in this social environment. PURPOSE: In this study, we explored the association between the outcomes of IVF treatment and anxiety, depression, marital satisfaction, communication, sexual relationship and social support. METHODS: A cross-sectional study was conducted. A total of 202 Chinese men who received IVF treatment for the first time were investigated using socio-demographic questionnaire, Self-Rating Anxiety Scale, Self-Rating Depression Scale, ENRICH Marital Inventory and Social Support Rating Scale on the first day of IVF treatment. RESULTS: The overall prevalence of depression and anxiety was 49.1% and 27.2%, respectively. Subjects with IVF failure had higher levels of depression and anxiety, lower levels of "Marital satisfaction", "communication" and "Sexual relationship" and social support. Logistic regression analysis indicated that depression, anxiety, marital satisfaction and sexual relationship were independent predictors of IVF failure. CONCLUSION: The prevalence of depression and anxiety in Chinese men undergoing IVF was higher than that in other countries. These findings suggest that anxiety, depression, marital satisfaction, and sexual relationship are important factors leading to IVF failure. Therefore, it is important to provide psychological aid to male patients undergoing IVF treatment.
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Fertilização in vitro , Infertilidade Masculina/epidemiologia , Ansiedade , China/epidemiologia , Estudos Transversais , Depressão , Humanos , Infertilidade Masculina/psicologia , Masculino , Apoio SocialRESUMO
Microglia are the main immunocompetent and phagocytic cells in Alzheimer's disease (AD). Bone marrow-derived microglia have been demonstrated to be more effective in antigen presentation and phagocytosis than inherent microglia in AD. Thus, microglia have received much attention in the pathogenesis of AD. The herbal medicine Juzen-taiho-to (JTT) has been reported to reduce ß-amyloid (Aß) burden in the mouse brain of an AD model. In this study, we explored the effects of JTT on the migration and differentiation of bone marrow-derived cells in the mouse brain of acutely induced AD. To chase bone marrow-derived cells, we made a chimeric mouse line in C57BL/6 by transplanting fresh bone marrow cells, isolated from the transgenic mice expressing enhanced green fluorescent protein gene. The chimeric mice were orally administrated with JTT or distilled water, and were left untreated or given intrahippocampal injection of fibrillar Aß 1-42 (fAß42) or vehicle. In the hippocampus of the vehicle-injected mouse, JTT treatment for 37 days caused a significant increase in the number of microglial cells. In the fAß42-injected mouse hippocampus, a larger number of bone marrow-derived cells were detected in JTT-treated mice than control mice in the non-neighboring regions of the fAß42-injected site but not around the injected site. These results suggest that JTT might contribute to the reduction of Aß burden and the immune surveillance in non-pathological as well as pathological brain regions. The results also implicate the therapeutic potential of JTT in AD.
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Peptídeos beta-Amiloides/efeitos adversos , Células da Medula Óssea/citologia , Transplante de Medula Óssea , Encéfalo/patologia , Diferenciação Celular , Medicamentos de Ervas Chinesas/uso terapêutico , Microglia/citologia , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Antígeno CD11b/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Galinhas , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Citometria de Fluxo , Proteínas de Fluorescência Verde/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Imuno-Histoquímica , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Fenótipo , Irradiação Corporal TotalRESUMO
BACKGROUND: Hypoxic-ischemic brain damage (HIBD) is a prevalent brain injury with high mortality and morbidity. It results from hypoxia and ischemia of the brain due to various perinatal factors. A previous study showed that knockdown of programmed cell death factor 4 (PDCD4) could reduce infarction injury resulting from ischemia/reperfusion injury. However, exact mechanism by which PDCD4 acts in HIBD is not yet understood. Our aim in present investigation was to investigate the function and mechanism of PDCD4 in alleviating HIBD. METHODS: An HIBD model was developed using neonatal rats. After 48 h of modeling, short-term neurological function was evaluated and the brain tissue removed for assessment of cerebral infarct volume and brain water content (BWC). A cell model of oxygen glucose deprivation/reoxygenation (OGD/R) was also constructed. Overexpression or knockdown of insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3) or PDCD4 was performed in pretreated cells. RESULTS: The geotaxis reflex time, cerebral infarct volume, and BWC all increased after HIBD in this neonatal rat model. Additionally, the levels of PDCD4 and of the N6-Methyladenosine (m6A) reader protein IGF2BP3 were increased in HIBD rats and OGD/R-stimulated pheochromocytoma (PC12) cells relative to controls. Moreover, OGD/R-stimulated pheochromocytoma PC12 cells showed decreased cell viability, increased apoptosis, and elevated Interleukin 6 (IL-6), Interleukin 1 ß (IL-1ß), and tumor necrosis factor-α (TNF-α) contents. These features were reversed after knocking down IGF2BP3. The interaction between IGF2BP3 protein and PDCD4 mRNA was confirmed by RNA immunoprecipitation and RNA pull-down assays. Furthermore, knockdown of IGF2BP3 in OGD/R-stimulated PC12 cells reduced cell damage via down-regulation of PDCD4. Finally, the IGF2BP3/PDCD4 axis alleviated OGD/R-induced cell injury in primary cortical neurons (PCNs). CONCLUSIONS: PDCD4 and m6A reader protein IGF2BP3 were up-regulated in an HIBD neonatal rat model. Knockdown of IGF2BP3 in OGD/R-stimulated PC12 cells or PCNs alleviated cell damage through reducing PDCD4.
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Proteínas Reguladoras de Apoptose , Regulação para Baixo , Técnicas de Silenciamento de Genes , Hipóxia-Isquemia Encefálica , Proteínas de Ligação a RNA , Ratos Sprague-Dawley , Animais , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas Reguladoras de Apoptose/genética , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/genética , Hipóxia-Isquemia Encefálica/patologia , Ratos , Células PC12 , Animais Recém-Nascidos , Modelos Animais de Doenças , MasculinoRESUMO
Inflammation-induced intestinal epithelial barrier (IEB) dysfunction is one of the important reasons for the occurrence and development of intestinal inflammatory-related diseases, including ulcerative colitis (UC), Crohn's disease and necrotizing enterocolitis (NEC). Dragon's blood (DB) is a traditional Chinese medicine and has been clinically used to treat UC. However, the protective mechanism of DB on intestinal inflammatory-related diseases has still not been elucidated. The present study aimed to explore the protection mechanism of DB on IEB dysfunction in rat ileum and human colorectal adenocarcinoma cells (Caco-2)/human umbilical vein endothelial cells (HUVECs) coculture system induced by lipopolysaccharide (LPS). DB could ameliorate rat ileum mucosa morphological injury, reduce the accumulation of lipid-peroxidation products and increase the expression of junction proteins. DB also alleviated LPS-induced Caco-2 cells barrier integrity destruction in Caco-2/ HUVECs coculture system, leading to increased trans-endothelial electrical resistance (TEER), reduced cell permeability, and upregulation of expressions of F-actin and junction proteins. DB contributed to the assembly of actin cytoskeleton by upregulating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway and contributed to the formation of intercellular junctions by downregulating TLR4-MyD88-NF-κB pathway, thus reversing LPS-induced IEB dysfunction. These novel findings illustrated the potential protective mechanism of DB on intestinal inflammatory-related diseases and might be useful for further clinical application of DB.
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Mucosa Intestinal , Lipopolissacarídeos , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Humanos , Células CACO-2 , Receptor 4 Toll-Like/metabolismo , Animais , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/toxicidade , Ratos , Transdução de Sinais/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Masculino , Regulação para Cima/efeitos dos fármacos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: Limited evidence on home care and need for long-term individualized follow-up highlight the importance of developing an Internet-based follow-up platform to support caregivers of children with Bronchiolitis Obliterans (BO). This Study aims to explore and test the potential benefits of this platform by comparing family management, medication compliance and clinical systems. STUDY DESIGN AND METHODS: A two-arm, single-blind randomized controlled trial was conducted on 168 children with BO and their families from January 2022 to October 2022. Families were randomly divided into Internet-based follow-up group and conventional follow-up group with a ratio of 1:1. Scores of family management measures (FaMM), 8-item of Morisky Medication Adherence (8-MMAS) and BO clinical symptoms of both groups were collected at three points of time: the day of discharge (T1), 3 months after discharge (T2), and 6 months after discharge (T3). The changes of each group due to intervention were compared by repeated-measures ANOVA. RESULTS: 90 families completed the trial, including 48 in the Internet-based follow-up group and 42 in the conventional follow-up group. The results showed a significant difference in the group-by-time interaction on the scores of Child's Daily Life, Condition Management Ability and Parental Mutuality (p < 0.05). No group-by-time effect was found on the scores of View of Condition Impact and Family Life Difficulty. Scores of BO clinical symptoms and MMAS-8 showed intra-group, inter-group, and group-by-time effects. CONCLUSIONS: The Internet-based follow-up platform can empower caregivers in enhancing effective family management, improving medication compliance in children with BO, and relieving patients' clinical symptoms. TRIAL REGISTRATION: Chinese Clinical Trials Registry of ChiCTR2200065121 (04/28/2022).
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BACKGROUND: Epilepsy is a chronic neurological disorder that is more likely to be diagnosed in children. The main treatment involves long-term use of anti-epileptic drugs and above all, home care is of great importance. As there has not been a widely accepted home care protocols, simulating a home care environment is necessary for caregivers to develop skills of proper home care. This study aims to evaluate the effectiveness of a simulation training of family management style (STOFMS) for parents of children with epilepsy in China. METHODS: A randomized controlled trial was conducted on 463 children with epilepsy and their families. They were recruited from March 2020 to November 2022 and randomly assigned to the STOFMS group or the conventional group in a 1:1 ratio. Scores of family management measures, 8-item of Morisky Medication Adherence and epilepsy clinical symptom of both groups were collected at three points of time: within 24 h after admission (T0), 3 months after discharge (T1), and 6 months after discharge (T2). Changes due to intervention were compared across groups by repeated-measures ANOVA. The study report followed the CONSORT 2010 checklist. RESULTS: There were statistically significant differences between the two groups at T2. A considerable increase over the baseline was observed in the total management level score and subscale scores in the STOFMS group at T1, compared with essentially no change in the control group. In terms of medication adherence, the STOFMS group performance improved greatly at T1 and T2 compared with the control group. The same result was also found in clinical efficacy at T2 (p < 0.05). CONCLUSION: STOFMS is an effective intervention to improve family management level, treatment adherence and clinical efficacy for children with epilepsy. TRIAL REGISTRATION: The registration number is ChiCTR2200065128. Registered at 18 October 2022, http://www.medresman.org.cn.
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Epilepsia , Serviços de Assistência Domiciliar , Treinamento por Simulação , Criança , Humanos , Pais/educação , Epilepsia/terapia , CuidadoresRESUMO
Wernekink commissure syndrome is a rare midbrain syndrome, which selectively destroys the Wernekink commissure involving the decussation of superior cerebellar peduncle in midbrain. This syndrome may display a clinical picture: bilateral cerebellar ataxia, eye movement disorders, and palatal tremor. We present two cases of the Wernekink commissure syndrome with acute onset of bilateral cerebellar dysfunction confirmed by magnetic resonance imaging. One patient presented internuclear ophthalmoplegia, but neither showed palatal tremor. It is notable that the bilateral cerebellar dysfunction may be ascribed to midbrain lesion involving the Wernekink commissure, and it may be the sole manifestation of the midbrain lesion.
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Ataxia Cerebelar/diagnóstico , Mesencéfalo/patologia , Transtornos da Motilidade Ocular/diagnóstico , Palato/patologia , Tremor/diagnóstico , Idoso , Ataxia Cerebelar/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos da Motilidade Ocular/complicações , Síndrome , Tremor/complicaçõesRESUMO
Background: Depressive symptoms play an essential role in cognition decline, while the benefit and acceptability of treatments for depressive symptoms in cognitive impairment are still unknown. Objective: To comprehensively evaluate the comparative efficacy and acceptability of treatments for depressive symptoms in cognitive impairment based on the quantitative Bayesian network meta-analysis method (NMA). Method: We searched MEDLINE, Embase, the Cochrane Library, CINAHL, and PsycINFO from inception until August 2022 to identify randomized clinical trials (RCTs) evaluating treatments for depressive symptoms in cognitive impairment. Efficacy was evaluated by the Cornell Scale for Depression in Dementia (CSDD), the Hamilton Depression Rating Scale (HDRS), and the Geriatric Depression Scale (GDS) for depression; the Neuropsychiatric Inventory (NPI) and the Cohen-Mansfeld Agitation Inventory (CMAI) for behavior; and the Mini-Mental State Examination (MMSE) for cognition. Safety was evaluated by total adverse events (AEs), serious AEs, diarrhea, headache, and nausea. Results: In this study, 13,043 participants from 107 RCTs were included, involving 28 treatments and the discontinuation of antidepressants. On CSDD, aerobic exercise (MD -4.51, 95%CrI -8.60 to -0.37), aripiprazole (MD -1.85, 95%CrI -3.66 to -0.02), behavioral training (MD -1.14, 95%CrI -2.04 to -0.34), electrical current stimulation (MD -3.30, 95%CrI -5.94 to -0.73), massage (MD -12.67, 95%CrI -14.71 to -10.59), music therapy (MD -2.63, 95%CrI -4.72 to -0.58), and reminiscence therapy (MD -2.34, 95%CrI -3.51 to -1.25) significantly outperformed the placebo. On MMSE, cognitive stimulation therapy (MD 1.42, 95%CrI 0.49 to 2.39), electrical current stimulation (MD 4.08, 95%CrI 1.07 to 7.11), and reminiscence therapy (MD 1.31, 95%CrI 0.04 to 2.91) significantly outperformed the placebo. Additionally, no treatments showed a significantly higher risk than the placebo. Conclusion: Our NMAs indicated that non-pharmacological interventions were more efficacious and safe than pharmacological treatments for reducing depressive symptoms as well as improving cognitive impairment. Electrical current stimulation, aerobic exercise, and reminiscence therapy could be first recommended considering their beneficial performance on both depression and cognition. Hence, non-pharmacological treatments deserve more attention and extensive application and should at least be considered as an alternative or assistance in clinical settings. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021239621, identifier: CRD42021239621.
RESUMO
This study aimed to evaluate the impact of Nd:YAG laser capsulotomy on the incidence of pseudophakic retinal detachment (RD). The PubMed and Embase databases were searched for meta-analysis. Subgroup analyses were conducted according to study location, number of cases, mean follow-up time, and cataract procedure. The final analysis included 11 studies with 309 cases of RD in 65 117 eyes undergoing cataract surgery. Among them, 8232 eyes underwent Nd:YAG capsulotomy. This analysis demonstrated an increased risk for RD with Nd:YAG laser capsulotomy (relative risk [RR], 1.57; 95% CI, 1.17-2.12; P = .003; hazard ratio, 1.64; 95% CI, 1.03-2.62; P = .04). Subgroup analysis suggested somewhat stronger associations in Asian (RR, 4.54; 95% CI, 2.20-9.38; P < .0001) than in non-Asian populations (Americans, P = .12; Europeans and others, P = .21) and with extracapsular cataract extraction (RR, 2.97; 95% CI, 1.83-4.83; P < .0001) than with phacoemulsification (P = .95). To conclude, Nd:YAG laser capsulotomy may be associated with an increased risk for pseudophakic RD.
Assuntos
Opacificação da Cápsula , Extração de Catarata , Terapia a Laser , Lasers de Estado Sólido , Cápsula do Cristalino , Descolamento Retiniano , Opacificação da Cápsula/etiologia , Opacificação da Cápsula/cirurgia , Humanos , Lasers de Estado Sólido/uso terapêutico , Cápsula do Cristalino/cirurgia , Complicações Pós-Operatórias/cirurgia , Descolamento Retiniano/etiologia , Descolamento Retiniano/cirurgiaRESUMO
Semen Ziziphi Spinosae (SZS) has been extensively used in the daily diet as a functional food for neuroprotective health-benefit in China for many years. However, the neuroprotective mechanism of SZS associated with blood-brain barrier (BBB) integrity remains unexplored. The present study suggests SZS could protect against lipopolysaccharide (LPS)-induced BBB dysfunction. Proteomics indicate that 135 proteins in rat brain are significantly altered by SZS. These differentially expressed proteins are mainly clustered into cell-cell adhesion and adherens junctions, which are closely related with BBB integrity. SZS reversed LPS-induces BBB breakdown by activating the FAK-DOCK180-Rac1-WAVE2-Arp3 pathway. Molecular docking between signaling pathway proteins and identified SZS components in rat plasma reveals that 6"'-feruloylspinosin, spinosin, and swertisin strongly binds to signaling proteins at multiple amino acid sites. These novel findings suggest a health benefit of SZS in prevention of cerebral diseases and contributes to the further application of SZS as a functional food.