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Background: Ethylene oxide (EtO), a highly reactive organic compound with extensive industrial applications, poses significant health risks. The association between EtO exposure and stroke was not well established. This study examined the association between EtO exposure and stroke among US adults using data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES). Methods: We used appropriately weighted multifactorial logistic regression models to analyze the data and validated the findings with smoothed curve fitting. Stratified analysis and interaction assessments were performed to evaluate the robustness of the findings. Results: The study included 5,071 participants, balanced between men and women, with a stroke prevalence of 4.1%. Higher EtO levels were associated with rising rates of stroke (OR = 1.23, 95% CI: 1.06-1.42). Individuals in the top 25% group displayed a stroke prevalence 1.6 times higher than those in the bottom 25% group (OR = 1.60, 95%CI: 1.03-2.48). Stratified analysis demonstrated a significant positive association between EtO and stroke in individuals under 50 years (OR = 1.94, 95%CI: 1.38-2.72), while no significant association was found in those aged 50 and above (OR = 0.97, 95%CI: 0.83-1.14). Conclusion: This study identified a significant association between EtO exposure and stroke occurrence in young adults in the United States.
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BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the substantia nigra (SN). Activation of the neuroinflammatory response has a pivotal role in PD. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach for various nerve injuries, but there are limited reports on their use in PD and the underlying mechanisms remain unclear. METHODS: We investigated the effects of clinical-grade hypoxia-preconditioned olfactory mucosa (hOM)-MSCs on neural functional recovery in both PD models and patients, as well as the preventive effects on mouse models of PD. To assess improvement in neuroinflammatory response and neural functional recovery induced by hOM-MSCs exposure, we employed single-cell RNA sequencing (scRNA-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq) combined with full-length transcriptome isoform-sequencing (ISO-seq), and functional assay. Furthermore, we present the findings from an initial cohort of patients enrolled in a phase I first-in-human clinical trial evaluating the safety and efficacy of intraspinal transplantation of hOM-MSC transplantation into severe PD patients. RESULTS: A functional assay identified that transforming growth factor-ß1 (TGF-ß1), secreted from hOM-MSCs, played a critical role in modulating mitochondrial function recovery in dopaminergic neurons. This effect was achieved through improving microglia immune regulation and autophagy homeostasis in the SN, which are closely associated with neuroinflammatory responses. Mechanistically, exposure to hOM-MSCs led to an improvement in neuroinflammation and neural function recovery partially mediated by TGF-ß1 via activation of the anaplastic lymphoma kinase/phosphatidylinositol-3-kinase/protein kinase B (ALK/PI3K/Akt) signaling pathway in microglia located in the SN of PD patients. Furthermore, intraspinal transplantation of hOM-MSCs improved the recovery of neurologic function and regulated the neuroinflammatory response without any adverse reactions observed in patients with PD. CONCLUSIONS: These findings provide compelling evidence for the involvement of TGF-ß1 in mediating the beneficial effects of hOM-MSCs on neural functional recovery in PD. Treatment and prevention of hOM-MSCs could be a promising and effective neuroprotective strategy for PD. Additionally, TGF-ß1 may be used alone or combined with hOM-MSCs therapy for treating PD.
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Modelos Animais de Doenças , Células-Tronco Mesenquimais , Mucosa Olfatória , Doença de Parkinson , Fator de Crescimento Transformador beta1 , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Transplante de Células-Tronco Mesenquimais/métodos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Recuperação de Função Fisiológica , Fator de Crescimento Transformador beta1/metabolismoRESUMO
BACKGROUND: Cerebral ischemia-reperfusion (I/R) injury often leads to neuronal death through persistent neuroinflammatory responses. Recent research has unveiled a unique inflammatory programmed cell death mode known as PANoptosis. However, direct evidence for PANoptosis in ischemic stroke-induced neuronal death has not been established. Although it is widely thought that modulating the balance of microglial phenotypic polarization in cerebral I/R could mitigate neuroinflammation-mediated neuronal death, it remains unknown whether microglial polarization influences PANoptotic neuronal death triggered by cerebral I/R. Our prior study demonstrated that curcumin (CUR) preconditioning could boost the neuroprotective properties of olfactory mucosa-derived mesenchymal stem cells (OM-MSCs) in intracerebral hemorrhage. Yet, the potential neuroprotective capacity of curcumin-pretreated OM-MSCs (CUR-OM-MSCs) on reducing PANoptotic neuronal death during cerebral I/R injury through modulating microglial polarization is uncertain. METHODS: To mimic cerebral I/R injury, We established in vivo models of reversible middle cerebral artery occlusion (MCAO) in C57BL/6 mice and in vitro models of oxygen-glucose deprivation/reoxygenation (OGD/R) in HT22 neurons and BV2 microglia. RESULTS: Our findings indicated that cerebral I/R injury caused PANoptotic neuronal death and triggered microglia to adopt an M1 (pro-inflammatory) phenotype both in vivo and in vitro. Curcumin pretreatment enhanced the proliferation and anti-inflammatory capacity of OM-MSCs. The CUR-OM-MSCs group experienced a more pronounced reduction in PANoptotic neuronal death and a better recovery of neurological function than the OM-MSCs group. Bioinformatic analysis revealed that microRNA-423-5p (miRNA-423-5p) expression was obviously upregulated in CUR-OM-MSCs compared to OM-MSCs. CUR-OM-MSCs treatment induced the switch to an M2 (anti-inflammatory) phenotype in microglia by releasing miRNA-423-5p, which targeted nucleotide-binding oligomerization domain 2 (NOD2), an upstream regulator of NF-kappaB (NF-κB) and Mitogen-Activated Protein Kinase (MAPK) signaling pathways, to attenuate PANoptotic neuronal death resulting from cerebral I/R. CONCLUSION: This results provide the first demonstration of the existence of PANoptotic neuronal death in cerebral I/R conditions. Curcumin preconditioning enhanced the ameliorating effect of OM-MSCs on neuroinflammation mediated by microglia polarization via upregulating the abundance of miRNA-423-5p. This intervention effectively alleviates PANoptotic neuronal death resulting from cerebral I/R. The combination of curcumin with OM-MSCs holds promise as a potentially efficacious treatment for cerebral ischemic stroke in the future.
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Curcumina , Células-Tronco Mesenquimais , Camundongos Endogâmicos C57BL , Microglia , Fármacos Neuroprotetores , Mucosa Olfatória , Traumatismo por Reperfusão , Curcumina/farmacologia , Animais , Traumatismo por Reperfusão/tratamento farmacológico , Microglia/efeitos dos fármacos , Camundongos , Células-Tronco Mesenquimais/efeitos dos fármacos , Masculino , Fármacos Neuroprotetores/farmacologia , Mucosa Olfatória/efeitos dos fármacos , Infarto da Artéria Cerebral Média/tratamento farmacológico , Neurônios/efeitos dos fármacos , Necroptose/efeitos dos fármacos , Modelos Animais de DoençasRESUMO
BACKGROUND: The treatment for cerebral ischemia remains limited, and new therapeutic strategies are urgently needed. Exosome has shown great promise for the treatment of cerebral ischemia. Steroid receptor coactivator-3 (SRC-3) was reported to be involved in neurological performances. In this study, we aimed to investigate the protective effects of mesenchymal stem cell (MSC)-derived exosomes overexpressing SRC-3 on cerebral ischemia in mice. METHODS: The mice were treated with an intracerebroventricular injection of GFP-overexpressed exosomes (GFP-exo) and SRC-3-overexpressed exosomes (SRC3-exo) in a middle cerebral artery occlusion (MCAO) model of cerebral ischemia. RESULTS: The results showed that SRC3-exo treatment significantly inhibited lipid peroxidation and ferroptosis of the neurons subjected to oxygen-glucose deprivation. It further suppressed the activation of microglia and astrocytes, and decreased the production of pro-inflammatory cytokines in the brains of MCAO mice. Furthermore, SRC3-exo treatment reduced the water content of brain tissue and infarct size, which alleviated the neurological damage and improved neurological performances in the MCAO mice. CONCLUSIONS: Our results suggest that MSC-derived exosomes expressing SRC3 can be a therapeutic strategy for cerebral ischemia by inhibiting ferroptosis.
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Isquemia Encefálica , Exossomos , Ferroptose , Infarto da Artéria Cerebral Média , Células-Tronco Mesenquimais , Coativador 3 de Receptor Nuclear , Animais , Exossomos/metabolismo , Exossomos/transplante , Camundongos , Ferroptose/fisiologia , Células-Tronco Mesenquimais/metabolismo , Masculino , Isquemia Encefálica/metabolismo , Isquemia Encefálica/terapia , Coativador 3 de Receptor Nuclear/metabolismo , Coativador 3 de Receptor Nuclear/genética , Infarto da Artéria Cerebral Média/metabolismo , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Modelos Animais de Doenças , Astrócitos/metabolismo , Encéfalo/metabolismoRESUMO
Background: Short-chain fatty acids (SCFAs) are thought to play a key role in the microbe-gut-brain axis and involve in the pathogenesis of a variety of neurological diseases. This study aimed to identify research hotspots and evolution trends in SCFAs in central nervous diseases (CNS) and examine current research trends. Methods: The bibliometric analysis was performed using CiteSpace, and the results were visualized via network maps. Results: From 2002 to 2022, 480 publications in the database met the criteria. On the country level, China produced the highest number of publications, while the United States had the highest centrality. On the institutional level, University College Cork contributed to the most publications, and John F. Cryan from this university was the key researcher with considerable academic influence. The article, the role of short-chain fatty acids in microbiota-gut-brain, written by Boushra Dalile et al., in 2019 was the most cited article. Furthermore, the journal Nutrients had the maximum number of publications, while Plos One was the most cited journal. "Gut microbiome", "SCFAs", and "central nervous system" were the three most frequent keywords. Among them, SCFAs had the highest centrality. "Animal model" was the keyword with the highest burst strength, with the latest burst keywords being "social behavior", "pathogenesis", and "insulin sensitive". In addition, the research topics on SCFAs in CNS diseases from 2002 to 2022 mainly focused on following aspects: SCFAs plays a key role in microbe-gut-brain crosstalk; The classification and definition of SCFAs in the field of CNS; Several CNS diseases that are closely related to SCFAs research; Mechanism and translational studies of SCFAs in the CNS diseases. And the hotspots over the past 5 years have gradually increased the attention to the therapeutic potential of SCFAs in the CNS diseases. Conclusion: The research of SCFAs in CNS diseases is attracting growing attention. However, there is a lack of cooperation between countries and institutions, and additional measures are required to promote cooperation. The current evidence for an association between SCFAs and CNS diseases is preliminary and more work is needed to pinpoint the precise mechanism. Moreover, large-scale clinical trials are needed in the future to define the therapeutic potential of SCFAs in CNS diseases.
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Nanomaterials capable of dual therapeutic effects of chemodynamic therapy (CDT) and photothermal therapy (PTT) is an efficacious strategy in cancer treatment. It is still a challenge to achieve complete apoptosis of tumor tissue in CDT/PTT due to the poor permeability of nanomaterials in tumor tissue. Herein, we prepared a dual-source driven Pt/FePc@Mn-MOF spindle-like Janus nanomotor by a facile oriented connection growth method for computed tomography (CT) imaging-guided CDT and PTT. The high catalase (CAT)-like activity of nanomotors allows the generation of oxygen (O2) bubbles by catalyzing the decomposition of endogenous H2O2, which alleviates the hypoxic state of the tumor microenvironment (TME) and simultaneously drive nanomotors. Pt/FePc@Mn-MOF nanomotor with excellent photothermal conversion efficiency exhibited dual peroxidase (POD)-like and oxidase (OXD)-like activities, which can produce large amounts of ROS to obtain PTT enhanced CDT. Meanwhile, near-infrared light, as "optical brakes", can trigger Janus nanomotor to realize self-thermophoretic movement. Chemical/NIR-assisted autonomous propulsion can significantly improve the accumulation of Janus nanomotors in solid tumors and enhance their ability to penetrate tumor tissue, thus brings synergistic enhancement effect to PTT and CDT. Moreover, Mn-MOF in nanomotor can deplete the antioxidant GSH by redox reaction to release massive Mn2+, which introduce Mn2+-based CT imaging properties. This novel dual-source controlled Janus nanomotor offers great potential for multimodal therapeutic medical applications.
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Nanopartículas , Neoplasias , Humanos , Peróxido de Hidrogênio , Terapia Fototérmica , Tomografia Computadorizada por Raios X , Antioxidantes , Oxigênio , Neoplasias/diagnóstico por imagem , Neoplasias/tratamento farmacológico , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
[This corrects the article DOI: 10.1016/j.heliyon.2023.e17785.].
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Micro/nanomotors that can promote mass transport have attracted more and more research concern in the photocatalysis field. Here we first report a newly-designed hierarchical α-Fe2O3/ZnFe2O4/Mn2O3 magnetic micromotor as a heterogeneous photocatalyst for the degradation of cationic dye methylene blue (MB) from wastewater. The resulting three-dimensional (3D) flower-like hollow Janus micromotors are fabricated through a green and scalable strategy, in which each component has different functions. ZnFe2O4 microspheres serve as a magnetic scaffold for the nucleation and growth of α-Fe2O3 nanosheets and for the recycling of the micromachine. α-Fe2O3 nanosheets have shown great potential as an ideal semiconductor material for the photocatalytic decontamination of pollutants. Mn2O3 nanoparticles are mainly utilized as a catalyst to produce O2 bubbles to propel the autonomic movement of the micromotors in the presence of H2O2 fuel and also as a Fenton-like catalyst to decompose H2O2 to generate reactive oxygen species. Furthermore, the resultant micromotors exhibited linear-like motion form with an average speed of 189.1 µm s-1 in 5 wt% H2O2 solution. Moreover, the self-driven micromotors exhibited a superior catalytic degradation property toward MB, which was attributed to the synergistic effect of heterogeneous photocatalyst and the boosted micro-mixing and mass transfer caused by the vigorous motion of the micro-actuator. The possible degradation intermediates and passways of MB by α-Fe2O3/ZnFe2O4/Mn2O3 micromotor were identified with time of flight mass spectroscopy (TOF-MS). The 3D Janus micromotors have the potential to be used as a high-efficiency and active heterogeneous photocatalyst for the degradation of organic pollutants.
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Peróxido de Hidrogênio , Águas Residuárias , Peróxido de Hidrogênio/química , MicroesferasRESUMO
Objectives: To characterize the 100 most-cited articles in the field of Wilson's Disease (WD) to provide a general overview and reveal the historical developments classical studies, and new findings. Design: WD-related articles were searched on the Web of Science database. The 100 most-cited articles were retrieved and their descriptive statistics were analyzed. Data extraction and synthesis: The 100 most-cited articles in the field of WD were selected and several parameters, including citation count, citation density, first author, corresponding author, journal, country, institution, and keywords were extracted to assess the overall quality and impact of the articles. Results: Most of the selected 100 articles were published in the 1990s and 2000s, with the highest number of articles published in 2005. Citations per paper ranged from 100 to 1,631, with a mean number of citations of 199.03. The top 100 articles were published in 38 journals, and the majority were published in the Journal of Biological Chemistry. The most prominent research themes were clinical presentations, clinical trials, copper transport mechanisms, and dysregulation of copper metabolism. Prof. Svetlana Lutsenko, Prof. Peter Ferenci, Prof. George J. Brewer, and Prof. Diane W. Cox were among the most influential researchers in this field, while Euro-American countries were the most dominant in terms of research output. Keywords network analysis identified "Transporting ATPase," "ATP7B," and "Menkes disease" as the most influential keywords. Moreover, disease management, WD clinical phenotype, ATP7B function, and copper metabolism are potential hotspots in future WD research. Conclusions: This study reveals the most influential articles in the field of WD research. In addition, the major research themes and technological innovations in the field of WD worldwide are presented.
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BACKGROUND: Toll-like receptor 4 (TLR4) plays a critical role in ischemic brain injury by mediating the inflammatory response. The microRNA miR-185-5p suppresses inflammatory signaling by targeting TLR4. This study investigates whether overexpressing miR-182-5p in bone marrow-derived mesenchymal stem cells (BM-MSCs) could potentiate the neuroprotective effects of BM-MSCs in a mouse model of ischemic brain injury. METHODS: We isolated BM-MSCs from mice, transfected the cells with miR-182-5p mimic, determined their MSC lineage through flow cytometry analysis of surface markers, examined miR-182-5p and TLR4 expression levels, and injected them into mice undergone middle cerebral artery occlusion (MCAO). MSC transplanted mice were subjected to behavior assays to determine cognitive and motor functions and biochemical analysis to determine neuroinflammation and TLR4/NF-κB in the ischemic hemisphere. RESULTS: We found that BM-MSCs overexpressing miR-182-5p showed reduced TLR4 expression without affecting their MSC lineage. Mice transplanted with miR-182-5p overexpressing BM-MSCs after MCAO showed significantly improved cognitive and motor functions and reduced neuroinflammation, including suppressed microglial M1 polarization, reduced inflammatory cytokines, and inhibited TLR4/ NF-κB signaling. CONCLUSION: Our findings suggest that overexpressing miR-182-5p in BM-MSCs can enhance the neuroprotective effects of BM-MSCs against ischemic brain injury by suppressing TLR4-mediated inflammatory response.
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Lesões Encefálicas , Isquemia Encefálica , Células-Tronco Mesenquimais , MicroRNAs , Fármacos Neuroprotetores , Animais , Camundongos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , NF-kappa B/metabolismo , Medula Óssea/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Fármacos Neuroprotetores/metabolismo , Células-Tronco Mesenquimais/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/terapia , Isquemia Encefálica/metabolismo , Infarto da Artéria Cerebral Média/genética , Infarto da Artéria Cerebral Média/terapia , Infarto da Artéria Cerebral Média/metabolismo , Modelos Animais de Doenças , Citocinas/metabolismoRESUMO
Large quantities of landfill sludge (LS) with higher water content (WC) were stored underground, and excavation and re-dewatering of LS is a sustainable and economic strategy to save landfill space and reduce the leaching of contaminants. In this study, polyferric silicate sulfate (PFSS) was first applied in the conditioning of excavated LS, and the effects of the Si/Fe mass ratio and PFSS dosage on physicochemical properties, dewaterability and rheological properties were investigated. At the best Si/Fe of 0.18, PFSS conditioning obtained compact aggregates with the strongest internal structure, thus achieving the lowest WC. Large sludge flocs were formed, and slime and loosely-bound extracellular polymeric substances were effectively removed with the PFSS dosage above 100 mg/g dried solids, which made the WC to be lower than 51.4%. The whole mechanical compression process of conditioned LS can be described by the modified Terzaghi-Voigt model, and increasing the PFSS dosage induced the release of bound water and migration of the consolidation stage from ternary to secondary. PFSS is an economically sustainable conditioner for LS, integrating multiple functions such as charge neutralization, particle aggregation, interparticle bridging and skeleton building in one chemical.
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Esgotos , Instalações de Eliminação de Resíduos , Esgotos/química , Silicatos , Sulfatos , Eliminação de Resíduos Líquidos , Água/químicaRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) and MSCs-derived extracellular vesicles (EVs) have emerged as potential novel therapies for subarachnoid hemorrhage (SAH). However, their effects remain incompletely understood. We aim to comprehensively evaluate the effect of MSCs-derived therapies in rodent models of SAH. METHODS: We searched PubMed, EMBASE, and Web of Science up to September 2021 to identify studies that reported the effects of MSCs or MSCs-derived EVs in a rodent SAH model. Neurobehavioral score was extracted as the functional outcome, and brain water content was measured as the histopathological outcome. A random-effects model was used to calculate the standardized mean difference (SMD) and confidence interval (CI). RESULTS: Nine studies published from 2018 to 2021 met the inclusion criteria. Studies quality scores ranged from 5 to 10, with a mean value of 7.22. Our results revealed an overall positive effect of MSCs and MSCs-derived EVs on the neurobehavioral score with a SMD of - 2.21 (95% CI - 3.14, - 1.08; p < 0.0001). Meanwhile, we also found that MSCs and MSCs-derived EVs reduced brain water content by a SMD of - 2.09 (95% CI - 2.99, - 1.19; p < 0.00001). Significant heterogeneity among studies was observed, further stratified and sensitivity analyses did not identify the source of heterogeneity. CONCLUSIONS: Our results suggested that MSCs-derived therapies prominently improved functional recovery and reduced brain edema in the rodent models of SAH. Notably, the limitations of small sample size should be considered when interpreting the results, and large animal studies and human trials are needed for further investigation.
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Vesículas Extracelulares , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Hemorragia Subaracnóidea , Animais , Modelos Animais de Doenças , Vesículas Extracelulares/patologia , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/patologia , Roedores , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/terapiaRESUMO
Mesenchymal stem cells (MSCs) derived from the bone marrow (BM) are reported to protect against ischemic brain injury. This study aimed to investigate whether the steroid receptor cofactor 3 (SRC3) was involved in MSC-induced neuroprotection. BM-MSCs were isolated from wild-type (WT) and SRC3 knockout (SRC3-/-) mice and transplanted into mice with middle cerebral artery occlusion (MCAO). The MSC identification and differentiation were determined by flow cytometry and Alizarin Red S staining after osteogenic and adipogenic stimulations. The effects of MSCs on brain injury were assessed by brain water content, modified neurological severity score (mNSS), Morris water maze test, and open field test. Finally, the effects of MSCs on MCAO-induced oxidative stress were assessed by measuring the levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) and mRNA levels of SOD1, SOD2, and CAT. We found that SRC3 deficiency did not impact the MSC identification or osteogenic and adipogenic differentiation. MSC-SRC3-/- transplantation in mice that underwent the MCAO procedure exhibited diminished effects on suppression of brain edema, neurological deficits, cognitive disruption, locomotor impairment, and anxiety compared to comparable levels of MSC-WT. Finally, MSC-WT transplantation inhibited MCAO-induced oxidative stress, and the effects were significantly attenuated in MCAO mice transplanted with MSC-SRC3-/-. MSCs suppressed the MCAO-induced upregulation of MDA activity and the inhibition of SOD, GSH, SOD1, SOD2, and CAT levels, and SRC3-deficient MSCs showed significantly reduced effects. Our results indicate that SRC3 plays an important role in mediating the neuroprotective effects of MSCs in mice that experienced ischemic stroke.
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Isquemia Encefálica , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Receptores de Esteroides , Animais , Medula Óssea , CamundongosRESUMO
Non-platinum carbon-based catalysts have attracted much more attention in recent years because of their low cost and outstanding performance, and are regarded as one of the most promising alternatives to precious metal catalysts. Activated carbon (AC), which has a large specific surface area (SSA), can be used as a carrier or carbon source at the same time. In this work, stable pine peel bio-based materials were used to prepare large-surface-area activated carbon and then compound with cobalt phthalocyanine (CoPc) to obtain a high-performance cobalt/nitrogen/carbon (Co-N-C) catalyst. High catalytic activity is related to increasing the number of Co particles on the large-specific-area activated carbon, which are related with the immersing effect of CoPc into the AC and the rational decomposed temperature of the CoPc ring. The synergy with N promoting the exposure of CoNx active sites is also important. The Eonset of the catalyst treated with a composite proportion of AC and CoPc of 1 to 2 at 800 °C (AC@CoPc-800-1-2) is 1.006 V, higher than the Pt/C (20 wt%) catalyst. Apart from this, compared with other AC/CoPc series catalysts and Pt/C (20 wt%) catalyst, the stability of AC/CoPc-800-1-2 is 87.8% in 0.1 M KOH after 20,000 s testing. Considering the performance and price of the catalyst in a practical application, these composite catalysts combining biomass carbon materials with phthalocyanine series could be widely used in the area of catalysts and energy storage.
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Studies have demonstrated the potential of mesenchymal stem cell (MSC) administration to promote functional recovery in preclinical studies of multiple sclerosis (MS), yet the effects of MSCs on remyelination are poorly understood. We wished to evaluate the therapeutic effects of MSCs on functional and histopathological outcomes in MS; therefore, we undertook an updated systematic review and meta-analysis of preclinical data on MSC therapy for MS. We searched mainstream databases from inception to July 15, 2021. Interventional studies of therapy using naïve MSCs in in vivo rodent models of MS were included. From each study, the clinical score was extracted as the functional outcome, and remyelination was measured as the histopathological outcome. Eighty-eight studies published from 2005 to 2021 met the inclusion criteria. Our results revealed an overall positive effect of MSCs on the functional outcome with a standardized mean difference (SMD) of -1.99 (95% confidence interval (CI): -2.32, -1.65; p = 0.000). MSCs promoted remyelination by an SMD of -2.31 (95% CI: -2.84, -1.79; p = 0.000). Significant heterogeneity among studies was observed. Altogether, our meta-analysis indicated that MSC administration improved functional recovery and promoted remyelination prominently in rodent models of MS.
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Transplante de Células-Tronco Mesenquimais/métodos , Esclerose Múltipla/terapia , Animais , Feminino , Humanos , Masculino , Camundongos , Viés de Publicação , RatosRESUMO
Estrogen is neuroprotective in brain injury models, and steroid receptor cofactor 3 (SRC3) mediates estrogen signaling. We aimed to investigate whether and how SRC3 is involved in the neuroprotective effects of 17ß-estradiol (E2) in a mouse model of intracerebral hemorrhage (ICH). Ovariectomized female mice were treated with E2 after autologous blood injection-induced ICH. Brain damage was assessed by neurological deficit score, brain water content, and oxidative stress levels. Blood-brain barrier (BBB) integrity was evaluated by Evan's blue extravasation and claudin-5, ZO-1, and occludin levels. SRC3 expression and PI3K/Akt signaling pathway were examined in ICH mice treated with E2. The effect of SRC3 on E2-mediated neuroprotection was determined by examining neurological outcomes in SRC3-deficient mice undergone ICH and E2 treatment. We found that E2 alleviated ICH-induced brain edema and neurological deficits, protected BBB integrity, and suppressed oxidative stress. E2 enhanced SRC3 expression and PI3K-/Akt signaling pathway. SRC3 deficiency abolished the protective effects of E2 on ICH-induced neurological deficits, brain edema, and BBB integrity. Our results suggest that E2 suppresses ICH-induced brain injury and SRC3 plays a critical role in E2-mediated neuroprotection.
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Edema Encefálico , Lesões Encefálicas , Coativador 3 de Receptor Nuclear , Animais , Barreira Hematoencefálica , Edema Encefálico/tratamento farmacológico , Edema Encefálico/etiologia , Hemorragia Cerebral/complicações , Hemorragia Cerebral/tratamento farmacológico , Modelos Animais de Doenças , Estradiol , Feminino , Camundongos , Estresse Oxidativo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de SinaisRESUMO
Intracerebral hemorrhage (ICH) causes long term neurological abnormality or death. Oxidative stress is closely involved in ICH mediated brain damage. Steroid receptor cofactor 3 (SRC-3), a p160 family member, is widely expressed in the brain and regulates transactivation of Nrf2, a key component of antioxidant response. Our study aims to test if SRC-3 is implicated in ICH mediated brain injury. We first examined levels of SRC-3 and oxidative stress in the brain of mice following ICH and analyzed their correlation. Then ICH was induced in wild type (WT) and SRC-3 knock out mice and how SRC-3 deletion affected ICH induced brain damage, oxidative stress and behavioral outcome was assessed. We found that SRC-3 mRNA and protein expression levels were reduced gradually after ICH induction in WT mice along with an increase in oxidative stress levels. Correlation analysis revealed that SRC-3 mRNA levels negatively correlated with oxidative stress. Deletion of SRC-3 further increased ICH induced brain edema, neurological deficit score and oxidative stress and exacerbated ICH induced behavioral abnormality including motor dysfunction and cognitive impairment. Our findings suggest that SRC-3 is involved in ICH induced brain injury, probably through modulation of oxidative stress.
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Hemorragia Cerebral/metabolismo , Modelos Animais de Doenças , Doenças do Sistema Nervoso/metabolismo , Coativador 3 de Receptor Nuclear/deficiência , Estresse Oxidativo/fisiologia , Animais , Hemorragia Cerebral/genética , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Doenças do Sistema Nervoso/genética , Coativador 3 de Receptor Nuclear/genéticaRESUMO
Guillain-Barré syndrome (GBS) is an acute inflammatory polyradiculoneuropathy in which most patients have cranial nerve involvement, with facial nerve involvement being the most common. However, delayed facial palsy (DFP) with asymmetric facial palsy is a rare manifestation of GBS, and the mechanism is unclear. We report a case of GBS combined with delayed unilateral facial palsy and review previously reported cases of GBS combined with DFP. A total of 28 cases of GBS with DFP, including the case in this report, were included in this study. The occurrence of DFP may be related to early subclinical demyelination of the facial nerve, the blood-nerve barrier of the facial nerve, facial movement, and descending reversible paralysis. The occurrence of unilateral facial palsy may be related to Campylobacter jejuni, specific anti-ganglioside antibodies, and the site of central nervous system anatomical involvement. There is no evidence that immunotherapy is related to the shortening of DFP course and improving patients' prognosis.
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A series of carbon and phthalocyanine catalysts were prepared with uniform and stretchable sunflower straw biological materials as the carbon source and inexpensive copper phthalocyanine (CuPc) pigment as a nitrogen doping source by a facile high-temperature carbonization method. This kind of biomass carbon material sunflower straw with abundant pore structure and sponge-like expansion and contraction functions can not only be used as a source of porous carbon in biomass carbon materials, but also as a carbon carrier with high specific surface area to provide nanoparticle adhesion sites. When it was immersed in the copper phthalocyanine pigment solution, more active sites could be exposed, so that CuPc particles could be uniformly doped and distributed on the porous carbon material. As a result, thanks to the doping of nitrogen atoms and the improvement of graphitization degree, the composite catalyst treated at 800 °C (CuPc@C-800) exhibits a porous structure with a 38 mV lower on-set potential and a high stability of 87.4% compared to commercial Pt/C (20%) catalyst. These results demonstrate that CuPc@C series composite catalysts have a splendid electrochemical performance in oxygen reduction reaction catalysts, which can start a new direction for later workers to study combining the properties of biomass carbon material and the phthalocyanine series of catalysts.
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BACKGROUND: Listeria monocytogenes (L. monocytogenes) is a facultative intracellular bacterial pathogen which can invade different mammalian cells and reach to the central nervous system (CNS), leading to meningoencephalitis and brain abscesses. In the diagnosis of L. monocytogenes meningoencephalitis (LMM), the traditional test often reports negative owing to the antibiotic treatment or a low number of bacteria in the cerebrospinal fluid. To date, timely diagnosis and accurate treatment remains a challenge for patients with listeria infections. CASE PRESENTATION: We present the case of a 66-year-old woman whose clinical manifestations were suspected as tuberculous meningoencephalitis, but the case was finally properly diagnosed as LMM by next-generation sequencing (NGS). The patient was successfully treated using a combined antibacterial therapy, comprising ampicillin and trimethoprim-sulfamethoxazole. CONCLUSION: To improve the sensitivity of LMM diagnosis, we used NGS for the detection of L. monocytogenes. Hence, the clinical utility of this approach can be very helpful since it provides quickly and trust results.