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AIM OF THE STUDY: We evaluated whether an artificial intelligence (AI)-driven robot cardiopulmonary resuscitation (CPR) could improve hemodynamic parameters and clinical outcomes. METHODS: We developed an AI-driven CPR robot which utilizes an integrated feedback system with an AI model predicting carotid blood flow (CBF). Twelve pigs were assigned to the AI robot group (n = 6) and the LUCAS 3 group (n = 6). They underwent 6 min of CPR after 7 min of ventricular fibrillation. In the AI robot group, the robot explored for the optimal compression position, depth and rate during the first 270-second period, and continued CPR with the optimal setup during the next 90-second period and beyond. The primary outcome was CBF during the last 90-second period. The secondary outcomes were coronary perfusion pressure (CPP), end-tidal carbon dioxide level (ETCO2) and return of spontaneous circulation (ROSC). RESULTS: The AI model's prediction performance was excellent (Pearson correlation coefficient = 0.98). CBF did not differ between the two groups [estimate and standard error (SE), -23.210 ± 20.193, P = 0.250]. CPP, ETCO2 level and rate of ROSC also did not show difference [estimate and SE, -0.214 ± 7.245, P = 0.976 for CPP; estimate and SE, 1.745 ± 3.199, P = 0.585 for ETCO2; 5/6 (83.3%) vs. 4/6 (66.7%), P = 1.000 for ROSC). CONCLUSION: This study provides proof of concept that an AI-driven CPR robot in porcine cardiac arrest is feasible. Compared to a LUCAS 3, an AI-driven CPR robot produced comparable hemodynamic and clinical outcomes.
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PURPOSE: Although multiple filgrastim biosimilars are now available in the United States, no studies comparing clinical outcomes between products have been reported. This analysis evaluated real-world outcomes of filgrastim-aafi and filgrastim-sndz in patients with select solid tumors receiving myelosuppressive chemotherapy to compare the two filgrastim biosimilars. METHODS: This was an observational, noninferiority, cohort study of patients from three integrated health care systems who received myelosuppressive chemotherapy and were prophylactically initiated on filgrastim-sndz between January and November 2021 or filgrastim-aafi between June and November 2022. Patients were followed from filgrastim biosimilar initiation until the start of their next chemotherapy cycle. The primary outcome of severe neutropenia was analyzed using a binary noninferiority test with a 5% upper margin. Secondary outcomes included the incidence of emergency department or hospital encounters due to febrile neutropenia and systemic antibiotic/antifungal medication use. If noninferiority was met, adjusted logistic regression modeling was conducted. RESULTS: A total of 2,730 patients who initiated filgrastim-aafi (n = 880) or filgrastim-sndz (n = 1,850) during the study period were included. The overall mean age was 55 years, 87.4% were female, 42.3% were White, and 76.6% had breast cancer. Severe neutropenia occurred in 1.8% and 1.7% of patients initiated on filgrastim-aafi and filgrastim-sndz, respectively (P < .01 for noninferiority). The adjusted odds ratio for severe neutropenia with filgrastim-aafi compared with filgrastim-sndz was 0.91 (95% CI, 0.49 to 1.68; P = .76). Noninferiority was met for all secondary outcomes (P < .01), and there were no adjusted statistically significant differences between the groups (all P > .05). CONCLUSION: Among patients with select solid tumors receiving myelosuppressive chemotherapy, severe neutropenia outcomes were comparable between filgrastim-aafi and filgrastim-sndz biosimilars. Findings from this study may support utilization of different filgrastim biosimilars in clinical practice.
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Extensive research has been conducted on the in vitro mass propagation of pear (Pyrus spp.) trees through vegetative propagation, demonstrating high efficiency in shoot multiplication across various pear species. However, the low in vitro rooting rates remain a significant barrier to the practical application and commercialization of mass propagation. This study aims to determine the favorable conditions for inducing root formation in the in vitro microshoots of Pyrus genotypes. The base of the microshoots was exposed to a high concentration (2 mg L-1) of auxins (a combination of IBA and NAA) for initial root induction at the moment when callus formation begins. The microshoots were then transferred to an R1 medium (1/2 MS with 30 g L-1 sucrose without PGRs) to promote root development. This method successfully induced rooting in three European pear varieties, one Asian pear variety, and a European-Asian hybrid, resulting in rooting rates of 66.7%, 87.2%, and 100% for the European pear (P. communis), 60% for the Asian pear (P. pyrifolia), and 83.3% for the hybrid pear (P. pyrifolia × P. communis) with an average of 25 days. In contrast, the control group (MS medium) exhibited rooting rates of 0-13.3% after 60 days of culture. These findings will enhance in vitro root induction for various pear varieties and support the mass propagation and acclimatization of pear. The in vitro root induction method developed in this study has the potential for global commercial application in pear cultivation.
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GPR55 is a receptor for lysophosphatidylinositols (LPIs) in digestive metabolites. Overnutrition leads to obesity, insulin resistance, and increased LPI levels in the plasma. The involvement of LPIs and GPR55 in adiposity, hepatic steatosis, and atherosclerosis has been previously elucidated. However, the therapeutic efficacy of GPR55 antagonists against obesity-induced airway inflammation has not been studied. The present study investigated whether CID16020046, a selective antagonist of GPR55, could modulate obesity-induced airway inflammation caused by a high-fat diet (HFD) in C57BL/6 mice. Administration of CID16020046 (1 mg/kg) inhibits HFD-induced adiposity and glucose intolerance. Analysis of immune cells in BALF showed that CID16020046 inhibited HFD-induced increase in immune cell infiltration. Histological analysis revealed the HFD induced hypersecretion of mucus and extensive fibrosis in the lungs. CID16020046 inhibited these HFD-induced pathological features. qRT-PCR revealed the HFD-induced increase in the expression of Ifn-γ, Tnf-α, Il-6, Il-13, Il-17A, Il-1ß, Nlrp3, and Mpo mRNAs in the lungs. CID16020046 inhibited the HFD-induced increases in these genes. The expression levels of adipokines were regulated by the HFD and CID16020046. AdipoQ in the lungs and gonadal white adipose tissue was decreased by the HFD and reversed by CID16020046. In contrast, Lep was increased by the HFD and suppressed by CID16020046. The findings suggest the potential application of the GPR55 antagonist CID16020046 in obesity-induced airway inflammation.
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Dieta Hiperlipídica , Pulmão , Camundongos Endogâmicos C57BL , Obesidade , Receptores de Canabinoides , Animais , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/complicações , Camundongos , Dieta Hiperlipídica/efeitos adversos , Masculino , Pulmão/patologia , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Receptores de Canabinoides/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Inflamação/metabolismo , Adiposidade/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/antagonistas & inibidoresRESUMO
Poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (PEDOT:PSS), a conductive polymer, has gained popularity as the channel layer in organic electrochemical transistors (OECTs) due to its high conductivity and straightforward processing. However, difficulties arise in controlling its conductivity through gate voltage, presenting a challenge. To address this issue, aromatic amidine base, diazabicyclo[4.3.0]non-5-ene (DBN), is used to stabilize the doping state of the PEDOT chain through a reliable chemical de-doping process. Furthermore, the addition of the proton-penetrable material Nafion to the PEDOT:PSS channel layer induces phase separation between the substances. By utilizing a solution containing both PEDOT:PSS and Nafion as the channel layer of OECTs, the efficiency of ion movement into the channel from the electrolyte is enhanced, resulting in improved OECT performance. The inclusion of Nafion in the OECTs' channel layer modifies ion movement dynamics, allowing for the adjustment of synaptic properties such as pulse-paired facilitation, memory level, short-term plasticity, and long-term plasticity. This research aims to introduce new possibilities in the field of neuromorphic computing and contribute to biomimetic technology through the enhancement of electronic component performance.
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Cryopreservation is a promising method for the long-term preservation of plant germplasm, especially for vegetatively propagated species like freesias. In this study, we investigate streamlining the cryopreservation process for 'Sunny Gold' Freesia, starting from effective in vitro initiation and proliferation using various plant growth regulator combinations. We also assess the impact of subculture on regrowth rates after cryopreservation. The shoot tips were successfully initiated in vitro after sterilization. The shoots were multiplied an average of three times in media containing N6-benzyladenine and kinetin. The regrowth rates of non-cryopreserved shoot tips excised from different subculture cycles did not differ significantly, with rates of 44% observed for plants from more than five subcultures and 47% for those from three subcultures. However, only the shoot tips excised from cultures subjected to three subculture cycles were able to recover after cryopreservation, with a regrowth rate of 31%. Our findings lay the groundwork for the development of an efficient cryopreservation protocol for freesias in the future.
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The epithelial-mesenchymal transition (EMT) and fibroblast activation are major events in idiopathic pulmonary fibrosis pathogenesis. Here, we investigated whether growth arrest-specific protein 6 (Gas6) plays a protective role in lung fibrosis via suppression of the EMT and fibroblast activation. rGas6 administration inhibited the EMT in isolated mouse ATII cells 14 days post-BLM treatment based on morphologic cellular alterations, changes in mRNA and protein expression profiles of EMT markers, and induction of EMT-activating transcription factors. BLM-induced increases in gene expression of fibroblast activation-related markers and the invasive capacity of primary lung fibroblasts in primary lung fibroblasts were reversed by rGas6 administration. Furthermore, the hydroxyproline content and collagen accumulation in interstitial areas with damaged alveolar structures in lung tissue were reduced by rGas6 administration. Targeting Gas6/Axl signaling events with specific inhibitors of Axl (BGB324), COX-2 (NS-398), EP1/EP2 receptor (AH-6809), or PGD2 DP2 receptor (BAY-u3405) reversed the inhibitory effects of rGas6 on EMT and fibroblast activation. Finally, we confirmed the antifibrotic effects of Gas6 using Gas6-/- mice. Therefore, Gas6/Axl signaling events play a potential role in inhibition of EMT process and fibroblast activation via COX-2-derived PGE2 and PGD2 production, ultimately preventing the development of pulmonary fibrosis.
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Transição Epitelial-Mesenquimal , Fibroblastos , Peptídeos e Proteínas de Sinalização Intercelular , Animais , Camundongos , Ciclo-Oxigenase 2/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Pulmão/metabolismoRESUMO
Hypodontia, i.e., missing one or more teeth, is a relatively common human disease; however, oligodontia, i.e., missing six or more teeth, excluding the third molars, is a rare congenital disorder. Many genes have been shown to cause oligodontia in non-syndromic or syndromic conditions. In this study, we identified two novel PAX9 mutations in two non-syndromic oligodontia families. A mutational analysis identified a silent mutation (NM_006194.4: c.771G>A, p.(Gln257=)) in family 1 and a frameshift mutation caused by a single nucleotide duplication (c.637dup, p.(Asp213Glyfs*104)) in family 2. A minigene splicing assay revealed that the silent mutation resulted in aberrant pre-mRNA splicing instead of normal splicing. The altered splicing products are ones with an exon 4 deletion or using a cryptic 5' splicing site in exon 4. Mutational effects were further investigated using protein expression, luciferase activity assay and immunolocalization. We believe this study will not only expand the mutational spectrum of PAX9 mutations in oligodontia but also strengthen the diagnostic power related to the identified silent mutation.
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Tomato chlorosis virus (ToCV) is an emerging pathogen that cause severe yellow leaf disorder syndrome in tomato plants. In this study, we aimed to generate a recombinant ToCV tagged with green fluorescent protein (GFP) to enable real-time monitoring of viral infection in living plants. Transformation of the full-length cDNA construct of ToCV RNA1 into Escherichia coli resulted in instability issues, which were successfully overcome by inserting a plant intron into RNA1. Subsequently, a GFP tag was engineered into a cDNA construct of ToCV RNA2. The resulting recombinant ToCV-GFP could systemically infect Nicotiana benthamiana plants, and GFP expression was observed along the major veins. Utilizing ToCV-GFP, we also showed that ToCV engages in antagonistic relationships with two different tomato-infecting viruses in mixed infections in N. benthamiana. This study demonstrates the potential of ToCV-GFP as a valuable tool for the visual tracking of infection and movement of criniviruses in living plants.
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Crinivirus , Solanum lycopersicum , Animais , Crinivirus/genética , DNA Complementar/genética , Doenças das Plantas , Insetos Vetores , Plantas , Solanum lycopersicum/genéticaRESUMO
BACKGROUND: Recently, we developed a chest compression device that can move the chest compression position without interruption during CPR and be remotely controlled to minimize rescuer exposure to infectious diseases. The purpose of this study was to compare its performance with conventional mechanical CPR device in a mannequin and a swine model of cardiac arrest. MATERIALS AND METHODS: A prototype of a remote-controlled automatic chest compression device (ROSCER) that can change the chest compression position without interruption during CPR was developed, and its performance was compared with LUCAS 3 in a mannequin and a swine model of cardiac arrest. In a swine model of cardiac arrest, 16 male pigs were randomly assigned into the two groups, ROSCER CPR (n = 8) and LUCAS 3 CPR (n = 8), respectively. During 5 minutes of CPR, hemodynamic parameters including aortic pressure, right atrial pressure, coronary perfusion pressure, common carotid blood flow, and end-tidal carbon dioxide partial pressure were measured. RESULTS: In the compression performance test using a mannequin, compression depth, compression time, decompression time, and plateau time were almost equal between ROSCER and LUCAS 3. In a swine model of cardiac arrest, coronary perfusion pressure showed no difference between the two groups (p = 0.409). Systolic aortic pressure and carotid blood flow were higher in the LUCAS 3 group than in the ROSCER group during 5 minutes of CPR (p < 0.001, p = 0.008, respectively). End-tidal CO2 level of the ROSCER group was initially lower than that of the LUCAS 3 group, but was higher over time (p = 0.022). A Kaplan-Meier survival analysis for ROSC also showed no difference between the two groups (p = 0.46). CONCLUSION: The prototype of a remote-controlled automated chest compression device can move the chest compression position without interruption during CPR. In a mannequin and a swine model of cardiac arrest, the device showed no inferior performance to a conventional mechanical CPR device.
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Reanimação Cardiopulmonar , Parada Cardíaca , Masculino , Animais , Suínos , Projetos Piloto , Manequins , Parada Cardíaca/terapia , Pressão , HemodinâmicaRESUMO
Free fatty acid 3 receptor (FFA3; previously GPR41) is a G protein-coupled receptor that senses short-chain fatty acids and dietary metabolites produced by the gut microbiota. FFA3 deficiency reportedly exacerbates inflammatory events in asthma. Herein, we aimed to determine the therapeutic potential of FFA3 agonists in treating inflammatory diseases. We investigated the effects of N-(2,5-dichlorophenyl)-4-(furan-2-yl)-2-methyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxamide (AR420626), an FFA3 agonist, in in vivo models of chemically induced allergic asthma and eczema in BALB/c mice. Administration of AR420626 decreased the number of immune cells in the bronchoalveolar lavage fluid and skin. AR420626 suppressed inflammatory cytokine expression in the lung and skin tissues. Histological examination revealed that AR420626 suppressed inflammation in the lungs and skin. Treatment with AR420626 significantly suppressed the enhanced lymph node size and inflammatory cytokine levels. Overall, FFA3 agonist AR420626 could suppress allergic asthma and eczema, implying that activation of FFA3 might be a therapeutic target for allergic diseases.
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Asma , Eczema , Camundongos , Animais , Ácidos Graxos não Esterificados/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Asma/tratamento farmacológico , Citocinas/metabolismo , Camundongos Endogâmicos BALB C , Ovalbumina , Modelos Animais de DoençasRESUMO
Lead-based halide perovskite nanocrystals (PeNCs) have demonstrated remarkable potential for use in light-emitting diodes (LEDs). This is because of their high photoluminescence quantum yield, defect tolerance, tunable emission wavelength, color purity, and high device efficiency. However, the environmental toxicity of Pb has impeded their commercial viability owing to the restriction of hazardous substances directive. Therefore, Pb-free PeNCs have emerged as a promising solution for the development of eco-friendly LEDs. This review article presents a detailed analysis of the various compositions of Pb-free PeNCs, including tin-, bismuth-, antimony-, and copper-based perovskites and double perovskites, focusing on their stability, optoelectronic properties, and device performance in LEDs. Furthermore, we address the challenges encountered in using Pb-free PeNC-LEDs and discuss the prospects and potential of these Pb-free PeNCs as sustainable alternatives to lead-based PeLEDs. In this review, we aim to shed light on the current state of Pb-free PeNC LEDs and highlight their significance in driving the development of eco-friendly LED technologies.
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Graft-versus-host disease (GvHD) is a severe complication of hematopoietic stem cell transplantation driven by activated allogeneic T cells. Here, we identify a distinct subset of T cell factor-1 (TCF1)+ CD8+ T cells in mouse allogeneic and xenogeneic transplant models of acute GvHD. These TCF1+ cells exhibit distinct characteristics compared to TCF1- cells, including lower expression of inhibitory receptors and higher expression of costimulatory molecules. Notably, the TCF1+ subset displays exclusive proliferative potential and could differentiate into TCF1- effector cells upon antigenic stimulation. Pathway analyses support the role of TCF1+ and TCF1- subsets as resource cells and effector cells, respectively. Furthermore, the TCF1+ CD8+ T cell subset is primarily present in the spleen and exhibits a resident phenotype. These findings provide insight into the differentiation of allogeneic and xenogeneic CD8+ T cells and have implications for the development of immunotherapeutic strategies targeting acute GvHD.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Animais , Camundongos , Linfócitos T CD8-Positivos , Diferenciação Celular , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fenótipo , HumanosRESUMO
BACKGROUND: People experienced various stress and psychological responses to the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to examine the changes in emergency medical services (EMSs) utilization by self-harm patients in early pandemic and the impacts of physical distancing measures on the EMSs utilization by self-harm patients. METHODS: Data for all patients presenting to emergency departments (EDs) after self-harm injuries including self-poisoning were collected from the National ED Information System (NEDIS). Characteristics of patients in two study regions (urban versus rural) were compared. Weekly and annual ED visit rates after self-harm (VRSH) per 100,000 population were calculated. Mobile phone mobility index (MPMI) was calculated by dividing a region's aggregated mobile phone mobility by mid-year population. Joinpoint regression analysis was conducted to assess changes in 2020 over pre-pandemic years. Test for presence of joinpoint at the end of 2019 was performed. A cross-correlation function was used to estimate the maximal morphological similarity and lag time between changes in MPMI and VRSH. RESULTS: In 2020, in early phases of the pandemic, there was a moderate decline in self-harm-related ED visits to 30,797 from a continuously increasing trend seen in previous years. However, proportions of young people (50.1%) and females (62.3%) increased over previous years. VRSHs among women and young people aged 15-34 years showed higher levels in 2020 than in previous five years. There was a significant decrease in the proportion of patients transported directly from the scene. In addition, there was a polarization of mental state upon ED arrival from alert and unresponsive. The median correlation coefficient between MPMI values and VRSH values was 0.601 (interquartile range [IQR]: 0.539-0.619) in urban regions and 0.531 (IQR: 0.454-0.595) in rural regions, showing no statistically significant difference between the two. CONCLUSION: Physical distancing measures adopted to prevent the spread of transmittable diseases following the pandemic had the effect of decreasing ED visits due to self-harm. When the pandemic has ended, and daily life has been restored, it will be particularly important to pay attention to the increased numbers of self-harm patients expected to visit EDs compared to during the pandemic.
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COVID-19 , Comportamento Autodestrutivo , Humanos , Feminino , Adolescente , Pandemias , Distanciamento Físico , Estudos Retrospectivos , COVID-19/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/prevenção & controle , Comportamento Autodestrutivo/psicologia , Serviço Hospitalar de Emergência , República da Coreia/epidemiologiaRESUMO
Introduction: Growth-associated protein 43 (GAP-43) is known as a neuronal plasticity protein because it is widely expressed at high levels in neuronal growth cones during axonal regeneration. GAP-43 expressed in mature adult neurons is functionally important for the neuronal communication of synapses in learning and memory. Brain-derived neurotrophic factor (BDNF) is closely related to neurodegeneration and synaptic plasticity during the aging process. However, the molecular mechanisms regulating neurodegeneration and synaptic plasticity underlying the pathogenesis and progression of Alzheimer's disease (AD) still remain incompletely understood. Methods: Remarkably, the expressions of GAP-43 and BDNF perfectly match in various neurons in the Human Brain Atlas database. Moreover, GAP-43 and BDNF are highly expressed in a healthy adults' hippocampus brain region and are inversely correlated with the amyloid beta (Aß), which is the pathological peptide of amyloid plaques found in the brains of patients with AD. Results: These data led us to investigate the impact of the direct molecular interaction between GAP-43 and BDNF in hippocampal neuron fate. In this study, we show that GAP-43 and BDNF are inversely associated with pathological molecules for AD (Tau and Aß). In addition, we define the three-dimensional protein structure for GAP-43 and BDNF, including the predictive direct binding sites via analysis using ClusPro 2.0, and demonstrate that the deprivation of GAP-43 and BDNF triggers hippocampal neuronal death and memory dysfunction, employing the GAP-43 or BDNF knock-down cellular models and 5XFAD mice. Conclusion: These results show that GAP-43 and BDNF are direct binding partners in hippocampal neurons and that their molecular signaling might be potential therapeutic targets for AD.
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Recently, several studies have demonstrated that low-dose radiation (LDR) therapy has positively impacts on the treatment of Alzheimer's disease (AD). LDR suppresses the production of pro-neuroinflammation molecules and improves cognitive function in AD. However, it is unclear whether direct exposure to LDR causes beneficial effects and what mechanism is involved in neuronal cells. In this study, we first determined the effect of high-dose radiation (HDR) alone on C6 cells and SH-SY5Y cells. We found that SH-SY5Y cells were more vulnerable than C6 cells to HDR. Moreover, in neuronal SH-SY5Y cells exposed to single or multiple LDR, N-type cells showed decreased cell viability with increasing radiation exposure time and frequency, but S-type cells were unaffected. Multiple LDR increased proapoptotic molecules such as p53, Bax and cleaved caspase-3, and decreased anti-apoptotic molecule (Bcl2). Multiple LDR also generated free radicals in neuronal SH-SY5Y cells. We detected a change in the expression of the neuronal cysteine transporter EAAC1. Pretreatment with N-acetylcysteine (NAC) rescued the increased in EAAC1 expression and the generation of ROS in neuronal SH-SY5Y cells after multiple LDR. Furthermore, we verified whether the increased in EAAC1 expression induces cell defense or cell death promotion signaling. We showed that transient overexpression of EAAC1 reduced the multiple LDR-induced p53 overexpression in neuronal SH-SY5Y cells. Our results indicate that neuronal cells can be injured by increased production of ROS not only by HDR but also by multiple LDR, which suggests that combination treatment with anti-free radical agents such as NAC may be useful in multiple LDR therapy.
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Acetilcisteína , Neuroblastoma , Humanos , Acetilcisteína/farmacologia , Acetilcisteína/metabolismo , Apoptose , Espécies Reativas de Oxigênio/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Linhagem Celular Tumoral , Neuroblastoma/radioterapia , Neuroblastoma/metabolismo , Estresse Oxidativo , Sobrevivência CelularRESUMO
The abnormal accumulation and aggregation of the misfolded α-synuclein protein is the neuropathological hallmark of all α-synucleinopathies, including Parkinson's disease. The secreted proteins known as netrins (netrin-1, netrin-3, and netrin-4) are related to laminin and have a role in the molecular pathway for axon guidance and cell survival. Interestingly, only netrin-1 is significantly expressed in the substantia nigra (SN) of healthy adult brains and its expression inversely correlates with that of α-synuclein, which prompted us to look into the role of α-synuclein and netrin-1 molecular interaction in the future of dopaminergic neurons. Here, we showed that netrin-1 and α-synuclein directly interacted in pre-formed fibrils (PFFs) generation test, real time binding assay, and co-immunoprecipitation with neurotoxin treated cell lysates. Netrin-1 deficiency appeared to activate the dopaminergic neuronal cell death signal pathway via α-synuclein aggregation and hyperphosphorylation of α-synuclein S129. Taken together, netrin-1 can be a promising therapeutic molecule in Parkinson's disease. [BMB Reports 2023; 56(2): 126-131].
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Doença de Parkinson , alfa-Sinucleína , Humanos , alfa-Sinucleína/metabolismo , Doença de Parkinson/metabolismo , Neurônios Dopaminérgicos/metabolismo , Netrina-1/metabolismo , Substância Negra/metabolismo , Substância Negra/patologiaRESUMO
Neuregulin-1 (NRG1) is an epidermal growth factor family member with essential roles in the developing and adult nervous systems. In recent years, establishing evidence has collectively suggested that NRG1 is a new modulator of central nervous system (CNS) injury and disease, with multifaceted roles in neuroprotection, remyelination, neuroinflammation, and other repair mechanisms. NRG1 signaling exerts its effects via the tyrosine kinase receptors ErbB2-ErbB4. The NRG1/ErbB network in CNS pathology and repair has evolved, primarily in recent years. In the present study, we demonstrated that a unilateral microinjection of CoCl2 into the ventral hippocampus (vHPC) induced hypoxic insult and led to anxiety-related behaviors and deficit sociability in mice. NRG1 treatment significantly alleviated the CoCl2-induced increase of hypoxic-related molecules and behavioral abnormalities. Furthermore, NRG1 reduced the CoCl2-induced neuroinflammation and neuronal deficits in the vHPC or primary hippocampal neurons in mice. Collectively, these results suggest that NRG1 ameliorates hypoxia by alleviating synaptic deficits and behavioral abnormalities of the CoCl2-induced vHPC hypoxic model.
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Neuregulina-1 , Doenças Neuroinflamatórias , Camundongos , Animais , Neuregulina-1/metabolismo , Hipocampo/metabolismo , Comportamento Social , Ansiedade/tratamento farmacológicoRESUMO
Scutellaria baicalensis has long been used in Asian traditional medicine to prevent and treat suppurative dermatitis, allergic diseases, inflammation, hyperlipemia, and arteriosclerosis. Oroxylin A is a flavone present in Scutellaria baicalensis. Because the root extracts of Scutellaria baicalensis have been shown to have anti-dermatitis effects, the authors investigated the effects of oroxylin A on chemically induced atopic dermatitis (AD) in an in vivo AD model induced by 1-chloro-2,4-dinitrobenzene (CDNB) in BALB/c mice. CDNB-induced skin hypertrophy and accumulation of mast cells in the epidermis and dermis were significantly decreased by oroxylin A. Increased serum levels of immunoglobulin E, as well as pro-inflammatory chemokines and cytokines in the skin and lymph nodes, were significantly decreased by oroxylin A. Suppression of immune responses in the skin and lymph nodes by oroxylin A decreased the symptoms of AD. Thus, these results proved that oroxylin A is an effective component of Scutellaria baicalensis for treating the symptoms of AD.
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Dermatite Atópica , Camundongos , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/tratamento farmacológico , Pele , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Citocinas , Extratos Vegetais/farmacologia , Dinitrobenzenos/farmacologia , Camundongos Endogâmicos BALB CRESUMO
Face identification is useful for social interactions and its impairment can lead to severe social and mental problems. This ability is also remarkably important in applied settings, including eyewitness identification and ID verification. Several studies have demonstrated the potential of Transcranial Random Noise Stimulation (tRNS) to enhance different cognitive skills. However, research has produced inconclusive results about the effectiveness of tRNS to improve face identification. The present study aims to further explore the effect of tRNS on face identification using an unfamiliar face matching task. Observers firstly received either high-frequency bilateral tRNS or sham stimulation for 20 min. The stimulation targeted occipitotemporal areas, which have been previously involved in face processing. In a subsequent stage, observers were asked to perform an unfamiliar face matching task consisting of unaltered and pixelated face pictures. Compared to the sham stimulation group, the high-frequency tRNS group showed better unfamiliar face matching performance with both unaltered and pixelated faces. Our results show that a single high-frequency tRNS session might suffice to improve face identification abilities. These results have important consequences for the treatment of face recognition disorders, and potential applications in those scenarios whereby the identification of faces is primordial.