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1.
J Colloid Interface Sci ; 670: 124-131, 2024 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-38759267

RESUMO

Iron hydroxide (FeOOH) is a potential active component in iron-based electrocatalysts for water electrolysis. However, its catalytic performance is constrained by its slow oxygen evolution reaction (OER) kinetics. Herein, we synthesized a nanoflower-like FeCo-hydro(oxy)oxides composite with tunable Fe/Co ratios (Fex-Coy) on nickel foam (NF) via a one-step electrodeposition technique. This method allows for precise control over the morphology and composition of the hybrid nanoflowers. The optimized Fe9-Co1 discloses favorable OER performance with a low overpotential of 222 mV at 50 mA cm-2 and demonstrates good stability exceeding 60 h at 10 mA cm-2. Further, an assembled Fe9-Co1(+)||Pt/C(-) dual-electrode configuration achieves a low cell voltage of 1.73 V at the current density of 100 mA cm-2 for water splitting, with long-term stability for 70 h and minimal degradation. Studies indicate that the distinctive nanoflower morphology of Fe9-Co1 enhances active site exposure, while both FeOOH and reconstructed CoOOH serve as catalytic centers, contributing to the observed OER performance. This work introduces a facile approach for synthesizing OER electrocatalysts, underscoring the role of the high-valence state of Fe/Co as active sites in the OER process.

2.
Int J Mol Sci ; 25(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38674138

RESUMO

The Japanese pine sawyer Monochamus alternatus serves as the primary vector for pine wilt disease, a devastating pine disease that poses a significant threat to the sustainable development of forestry in the Eurasian region. Currently, trap devices based on informational compounds have played a crucial role in monitoring and controlling the M. alternatus population. However, the specific proteins within M. alternatus involved in recognizing the aforementioned informational compounds remain largely unclear. To elucidate the spatiotemporal distribution of M. alternatus chemosensory-related genes, this study conducted neural transcriptome analyses to investigate gene expression patterns in different body parts during the feeding and mating stages of both male and female beetles. The results revealed that 15 genes in the gustatory receptor (GR) gene family exhibited high expression in the mouthparts, most genes in the odorant binding protein (OBP) gene family exhibited high expression across all body parts, 22 genes in the odorant receptor (OR) gene family exhibited high expression in the antennae, a significant number of genes in the chemosensory protein (CSP) and sensory neuron membrane protein (SNMP) gene families exhibited high expression in both the mouthparts and antennae, and 30 genes in the ionotropic receptors (IR) gene family were expressed in the antennae. Through co-expression analyses, it was observed that 34 genes in the IR gene family were co-expressed across the four developmental stages. The Antenna IR subfamily and IR8a/Ir25a subfamily exhibited relatively high expression levels in the antennae, while the Kainate subfamily, NMDA subfamily, and Divergent subfamily exhibited predominantly high expression in the facial region. MalIR33 is expressed only during the feeding stage of M. alternatus, the MalIR37 gene exhibits specific expression in male beetles, the MalIR34 gene exhibits specific expression during the feeding stage in male beetles, the MalIR8 and MalIR39 genes exhibit specific expression during the feeding stage in female beetles, and MalIR8 is expressed only during two developmental stages in male beetles and during the mating stage in female beetles. The IR gene family exhibits gene-specific expression in different spatiotemporal contexts, laying the foundation for the subsequent selection of functional genes and facilitating the full utilization of host plant volatiles and insect sex pheromones, thereby enabling the development of more efficient attractants.


Assuntos
Besouros , Proteínas de Insetos , Receptores Odorantes , Transcriptoma , Animais , Besouros/genética , Besouros/metabolismo , Besouros/crescimento & desenvolvimento , Masculino , Feminino , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Perfilação da Expressão Gênica , Antenas de Artrópodes/metabolismo , Receptores Ionotrópicos de Glutamato/genética , Receptores Ionotrópicos de Glutamato/metabolismo
3.
Front Cell Infect Microbiol ; 14: 1362961, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38465234

RESUMO

Pine wood nematode disease is currently the most deadly forest disease in China, and the Monochamus alternatus is its primary vector. Controlling the M. alternatus is crucial for managing pine wood nematode disease. This study, based on the selected HasA (pGHKW4) secretory expression vector, used electroporation to combine the genetically modified high-toxicity toxin Cry3Aa-T with the entomopathogenic bacterium Yersinia entomophaga isolated from the gut of the M. alternatus. The SDS-PAGE and Western blotting techniques were employed to confirm the toxin protein's secretion capability. The engineered bacteria's genetic stability and effectiveness in controlling M. alternatus were assessed for their insecticidal activity. The results of the SDS-PAGE and Western blotting analyses indicate that the HasA system effectively expresses toxin protein secretion, demonstrates certain genetic stability, and exhibits high insecticidal activity against M. alternatus. This study constructed a highly toxic entomopathogenic engineered bacterial strain against M. alternatus larvae, which holds significant implications for controlling M. alternatus, laying the foundation for subsequent research and application of this strain.


Assuntos
Besouros , Inseticidas , Animais , Besouros/genética , Larva , Bactérias , Transporte Biológico
4.
Nanoscale ; 16(9): 4909-4918, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38334962

RESUMO

The electrocatalytic hydrogen evolution reaction (HER) is an efficient approach to convert sustainable energy sources into clean energy carriers, H2. Although various transition metal sulfides (TMSs) have been reported as promising alternatives to precious metal-based catalysts, the top catalyst among TMSs remains unclear as there is a dearth of high-quality studies that provide a 'fair' comparison of the performance of these TMSs synthesized and tested under the same conditions. In this work, layered transition metal sulfides (MS2: MoS2, WS2, VS2) and non-layered transition metal sulfides (MxSy: FeS2, CoSx, NiS) were obtained by a straightforward hydrothermal method, and thus a comprehensive platform was established for the comparison of the intrinsic activity of these materials in the HER. Experimental results demonstrate that layered MS2 exhibits better performance than non-layered MxSy in acidic electrolytes, while CoSx and NiS can catalyze hydrogen evolution more effectively under alkaline conditions due to structural reconfiguration. MoS2 shows the best HER performance in both acidic and alkaline electrolytes, particularly in 1 M KOH solution. This work provides guidance for the optimal design of transition metal electrocatalysts, and structural engineering strategies can be used to further enhance their catalytic activity.

5.
Brain Res ; 1828: 148790, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38272156

RESUMO

A strong relationship between Alzheimer's disease (AD) and vascular dysfunction has been the focus of increasing attention in aging societies. In the present study, we examined the long-term effect of scallop-derived plasmalogen (sPlas) on vascular remodeling-related proteins in the brain of an AD with cerebral hypoperfusion (HP) mouse model. We demonstrated, for the first time, that cerebral HP activated the axis of the receptor for advanced glycation endproducts (RAGE)/phosphorylated signal transducer and activator of transcription 3 (pSTAT3)/provirus integration site for Moloney murine leukemia virus 1 (PIM1)/nuclear factor of activated T cells 1 (NFATc1), accounting for such cerebral vascular remodeling. Moreover, we also found that cerebral HP accelerated pSTAT3-mediated astrogliosis and activation of the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome, probably leading to cognitive decline. On the other hand, sPlas treatment attenuated the activation of the pSTAT3/PIM1/NFATc1 axis independent of RAGE and significantly suppressed NLRP3 inflammasome activation, demonstrating the beneficial effect on AD.


Assuntos
Doença de Alzheimer , Camundongos , Animais , Doença de Alzheimer/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Plasmalogênios , Fatores de Transcrição NFI/metabolismo , Inflamassomos/metabolismo , Fator de Transcrição STAT3/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Remodelação Vascular
6.
J Colloid Interface Sci ; 660: 989-996, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38290325

RESUMO

The pursuit of efficient and economically viable catalysts for liquid/solid-state zinc-air batteries (ZABs) is of paramount importance yet presents formidable challenge. Herein, we synthesized a vacancy-rich cobalt/manganese oxide catalyst (Co/MnO@NC) stabilized on a nitrogen-doped mesoporous carbon (NC) nanosphere matrix by leveraging hydrothermal and high-temperature pyrolysis strategy. The optimized Co/MnO@NC demonstrates fast reaction kinetics and large limiting current densities comparable to commercial Pt/C in alkaline electrolyte for oxygen reduction reaction (ORR). Moreover, the Co/MnO@NC serves as an incredible cathode material for both liquid and flexible solid-state ZABs, delivering impressive peak power densities of 217.7 and 63.3 mW cm-2 and robust long-term stability (459 h), outperforming the state-of-the-art Pt/C and majority of the currently reported catalysts. Research indicates that the superior performance of the Co/MnO@NC catalyst primarily stems from the synergy between the heightened electrical conductivity of metallic Co and the regulatory capacity of MnO on adsorbed oxygen intermediates. In addition, the abundance of vacancies regulates the electronic configuration, and superhydrophilicity facilitates efficient electrolyte diffusion, thereby effectively ensuring optimal contact between the active site and reactants. Besides, the coexisting NC layer avoids the shedding of active sites, resulting in high stability. This work provides a viable approach for designing and advancing high-performance liquid/solid-state ZABs, highlighting the great potential of energy storage technology.

7.
Brain Res ; 1827: 148745, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38176520

RESUMO

A flavonoid, sudachitin, has been reported to show some beneficial health effects, including as an anti-inflammatory in LPS-stimulated macrophages, as well as improving glucose and lipid metabolism in mice fed a high-fat diet. In this study, we investigated the neuroprotective effect of sudachitin in the transient middle cerebral artery occlusion (tMCAO) mouse model. After daily pre-treatment of vehicle or sudachitin (5 or 50 mg/kg) for 14 days, mice (n = 76) were subjected to a sham operation or tMCAO for 45 min, and on the following days, they were treated daily with vehicle or sudachitin. The administration of sudachitin significantly reduced (p < 0.05) cerebral infarct volume and attenuated apoptosis, 5 days after tMCAO. Neurological impairment improved, the expression of an oxidative stress marker, 4-HNE, decreased, and the Sirt1/PGC-1α pathway was activated 5 days after tMCAO in the sudachitin-treated group. This is the first report to demonstrate the neuroprotective effect of sudachitin in cerebral ischemia/reperfusion injury mice model, probably by activating the Sirt1/PGC-1α axis. Sudachitin may be a promising supplement or therapeutic agent for reducing injury caused by ischemic strokes.


Assuntos
Glicosídeos , Fármacos Neuroprotetores , Acidente Vascular Cerebral , Camundongos , Animais , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Sirtuína 1 , Acidente Vascular Cerebral/tratamento farmacológico , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , Modelos Animais de Doenças
8.
Int J Mol Sci ; 24(24)2023 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-38139394

RESUMO

Knottin-type antimicrobial peptides possess exceptional attributes, such as high efficacy, low vulnerability to drug resistance, minimal toxicity, and precise targeting of drug sites. These peptides play a crucial role in the innate immunity of insects, offering protection against bacteria, fungi, and parasites. Knottins have garnered considerable interest as promising contenders for drug development due to their ability to bridge the gap between small molecules and protein-based biopharmaceuticals, effectively addressing the therapeutic limitations of both modalities. This work presents the isolation and identification of a novel antimicrobial peptide derived from Monochamus alternatus. The cDNA encodes a 56-amino acid knottin propeptide, while the mature peptide comprises only 34 amino acids. We have labeled this knottin peptide as MaK. Using chemically synthesized MaK, we evaluated its hemolytic activity, thermal stability, antibacterial properties, and efficacy against nematodes. The results of this study indicate that MaK is an exceptionally effective knottin-type peptide. It demonstrates low toxicity, superior stability, potent antibacterial activity, and the ability to suppress pine wood nematodes. Consequently, these findings suggest that MaK has potential use in developing innovative therapeutic agents to prevent and manage pine wilt disease.


Assuntos
Besouros , Miniproteínas Nó de Cistina , Nematoides , Animais , Miniproteínas Nó de Cistina/farmacologia , Peptídeos Antimicrobianos , Besouros/genética , Antibacterianos/farmacologia
9.
J Neuroimmune Pharmacol ; 18(4): 640-656, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37924374

RESUMO

Reduced uterine perfusion pressure (RUPP) is a well-established model which mimics many clinical features of preeclampsia (PE). Edaravone is a free radical scavenger with neuroprotective, antioxidant and anti-inflammatory effects against different models of cerebral ischemia. Therefore, we aimed to elucidate the different potential mechanisms through which PE affects fetal brain development using our previously established RUPP-placental ischemia mouse model. In addition, we investigated the neuroprotective effect of edaravone against the RUPP-induced fetal brain development alterations. On gestation day (GD) 13, pregnant mice were divided into four groups; sham (SV), edaravone (SE), RUPP (RV), and RUPP+edaravone (RE). SV and SE groups underwent sham surgeries, however, RV and RE groups were subjected to RUPP surgery via bilateral uterine ligation. Edaravone (3mg/kg) was injected via tail i.v. injection from GD 14-18. The fetal brains from different groups were collected on GD 18 and subjected to further investigations. The results showed that RUPP altered the structure of fetal brain cortex, induced neurodegeneration, increased the expression of the investigated pro-inflammatory markers; TNF-α, IL-6, IL-1ß, and MMP-9. RUPP resulted in microglial and astrocyte activation in the fetal brains, in addition to upregulation of Hif-1α and iNOS. Edaravone conferred a neuroprotective effect via alleviating the inflammatory response, restoring the neuronal structure and decreasing oxidative stress in the developing fetal brain. In conclusion, RUPP-placental ischemia mouse model could be a useful tool to further understand the underlying mechanisms of PE-induced child neuronal alterations. Edaravone could be a potential adjuvant therapy during PE to protect the developing fetal brain. The current study investigated the effects of a placenta-induced ischemia mouse model using reduced uterine perfusion pressure (RUPP) surgery on the fetal brain development and the potential neuroprotective effects of the drug edaravone. The study found that the RUPP model caused neurodegeneration and a pro-inflammatory response in the developing fetal brain, as well as hypoxia and oxidative stress. However, maternal injection of edaravone showed a strong ability to protect against these detrimental effects and target multiple pathways associated with neuronal damage. The current study suggests that the RUPP model could be useful for further study of the impact of preeclampsia on fetal brain development and that edaravone may have potential as a therapy for protecting against this damage.


Assuntos
Fármacos Neuroprotetores , Pré-Eclâmpsia , Humanos , Ratos , Criança , Gravidez , Feminino , Camundongos , Animais , Placenta/metabolismo , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Pré-Eclâmpsia/metabolismo , Edaravone/farmacologia , Edaravone/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos Sprague-Dawley , Encéfalo/metabolismo , Isquemia/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Modelos Animais de Doenças
10.
J Alzheimers Dis ; 96(2): 609-622, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37840489

RESUMO

BACKGROUND: Alzheimer's disease (AD) is characterized by cognitive dysfunction and memory loss that is accompanied by pathological changes to white matter. Some clinical and animal research revealed that AD combined with chronic cerebral hypoperfusion (CCH) exacerbates AD progression by inducing blood-brain barrier dysfunction and fibrinogen deposition. Rivaroxaban, an anticoagulant, has been shown to reduce the rates of dementia in atrial fibrillation patients, but its effects on white matter and the underlying mechanisms are unclear. OBJECTIVE: The main purpose of this study was to explore the therapeutic effect of rivaroxaban on the white matter of AD+CCH mice. METHODS: In this study, the therapeutic effects of rivaroxaban on white matter in a mouse AD+CCH model were investigated to explore the potential mechanisms involving fibrinogen deposition, inflammation, and oxidative stress on remyelination in white matter. RESULTS: The results indicate that rivaroxaban significantly attenuated fibrinogen deposition, fibrinogen-related microglia activation, oxidative stress, and enhanced demyelination in AD+CCH mice, leading to improved white matter integrity, reduced axonal damage, and restored myelin loss. CONCLUSIONS: These findings suggest that long-term administration of rivaroxaban might reduce the risk of dementia.


Assuntos
Doença de Alzheimer , Isquemia Encefálica , Remielinização , Substância Branca , Humanos , Camundongos , Animais , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Substância Branca/patologia , Rivaroxabana/uso terapêutico , Isquemia Encefálica/complicações , Fibrinogênio/uso terapêutico , Modelos Animais de Doenças
11.
Huan Jing Ke Xue ; 44(8): 4666-4678, 2023 Aug 08.
Artigo em Chinês | MEDLINE | ID: mdl-37694659

RESUMO

Exploring the spatial and temporal pattern evolution of habitat quality and carbon storage has a positive feedback effect on establishing an ecological security barrier and optimizing the spatial pattern of national land in the WeiBei Arid Plateau Region of Shaanxi. This study took the Weibei Plateau Region as a case study, simulated the spatial pattern of land use for different development scenarios of 2035 based on the PLUS model, and used the InVEST model to analyze the characteristics of habitat quality and carbon storage distribution in the study area from 1980 to 2020 and under multi-scenarios in the future. The results showed that:①the area of the low-grade habitat quality area in the study area expanded by 462.55 km2, and the carbon stock decreased by 7.85×106 t over the past 40 years, both of which showed an overall decreasing trend yearly. ②During the study period, the degraded habitat quality areas were concentrated in the northeastern part of the study area within Yan'an City, and the upgraded areas were distributed in strips near water sources or at higher elevations. The high carbon stock areas were concentrated in the complex terrain and sparsely populated areas in the study area, and the decreasing carbon stocked areas were scattered throughout the study area in a dotted pattern without obvious aggregation. ③In 2035, carbon stock decreased to different degrees in all states except for the natural development scenario. In the economic priority development scenario, the habitat quality low grade area covered 20787.41 km2, which was the simulated scenario of the fastest growth rate of low-grade area and the largest reduction of high-grade area compared with the early stage of the simulation. The results of this study can provide decision references and data support for low carbon green development and ecological restoration in the study area.

12.
Brain Res ; 1821: 148565, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37683777

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by the loss of synapses and neurons in the brain, and the accumulation of amyloid plaques. Aß oligomers (AßO) play a critical role in the pathogenesis of AD. Although there is increasing evidence to support the involvement of necroptosis in the pathogenesis of AD, the exact mechanism remains elusive. In the present study, we explored the effect of exogenous AßO injection on cell necroptosis and cognitive deficits in APP23 transgenic mice. We found that intrahippocampal injection of AßO accelerated the development of AD pathology and caused cognitive impairment in APP23 mice. Specifically, AßO injection significantly accelerated the accumulation of AßO and increased the expression level of phosphorylated-tau, and also induced necroptosis. Behavioral tests showed that AßO injection was associated with cognitive impairment. Furthermore, necroptosis induced by AßO injection occurred predominantly in microglia of the AD brain. We speculate that AßO increased necroptosis by activating microglia, resulting in cognitive deficits. Our results may aid in an understanding of the role played by AßO in AD from an alternative perspective and provide new ideas and evidence for necroptosis as a potential intervention and therapeutic target for AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doenças Neurodegenerativas , Camundongos , Animais , Peptídeos beta-Amiloides/metabolismo , Camundongos Transgênicos , Necroptose , Doença de Alzheimer/metabolismo , Disfunção Cognitiva/induzido quimicamente , Cognição
13.
Cell Transplant ; 32: 9636897231193069, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37615293

RESUMO

Human cord blood-endothelial progenitor cells (hCB-EPCs) isolated from the human umbilical cord can be used to repair damaged arteries. In this study, we used an animal model with pathological changes that mimics artery wall damage caused by stent retrievers in humans. We injected hCB-EPCs to investigate their effect on endothelial hyperplasia and dysfunction during intimal repair. Four groups were established based on the length of reperfusion (3 and 28 days), as well as the presence or absence of hCB-EPC therapy. Damage to the internal carotid artery was evaluated by hematoxylin-eosin and immunohistochemical staining. Stroke volume was not significantly different between non-EPC and EPC groups although EPC treatment alleviated intimal hyperplasia 28 days after intimal damage. Vascular endothelial growth factor (VEGF) and eNOS expression were significantly higher in the EPC-treated group than in the non-EPC group 3 days after intimal damage. In addition, MMP9 and 4HNE expression in the EPC-treated group was significantly lower than in the non-EPC group. Ultimately, this study found that venous transplantation of hCB-EPCs could inhibit neointimal hyperplasia, alleviate endothelial dysfunction, suppress intimal inflammation, and reduce oxidative stress during healing of intimal damage.


Assuntos
Células Progenitoras Endoteliais , Acidente Vascular Cerebral , Humanos , Ratos , Animais , Hiperplasia/metabolismo , Células Progenitoras Endoteliais/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Sangue Fetal , Artérias , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/metabolismo
14.
Children (Basel) ; 10(6)2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37371286

RESUMO

BACKGROUND: Cyberbullying is a globally shared youth problem-a problem of the interpersonal conflicts and contradictions that emerge during the socialization of adolescents. In particular, the issue of cyberbullying among rural left-behind adolescents needs to be given high priority. However, previous studies have paid little attention to how emotional neglect and social anxiety affect the cyberbullying behavior of rural left-behind adolescents. Therefore, this study was based on cognitive-behavioral theory to investigate the relationship between emotional neglect, cyberbullying, and social anxiety. METHODS: This study used the Emotional Neglect Scale, the Cyberbullying Scale, and the Social Anxiety Scale to conduct an anonymous online survey of 1429 rural left-behind adolescents in China. RESULTS: (1) Emotional neglect, social anxiety, and cyberbullying showed a two-way positive correlation. (2) The direct effect of emotional neglect on rural left-behind youth cyberbullying was significant (ß = 0.14, p < 0.00). (3) Social anxiety showed a partial mediating effect in the process of emotional neglect affecting rural left-behind youth cyberbullying, with a mediating effect of 26.32%. CONCLUSIONS: The results have positive implications for improving relevant policies and constructing mechanisms for protecting the rights and interests of rural left-behind adolescents.

15.
Redox Biol ; 63: 102727, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37156218

RESUMO

Adipose plasticity is critical for metabolic homeostasis. Adipocyte transdifferentiation plays an important role in adipose plasticity, but the molecular mechanism of transdifferentiation remains incompletely understood. Here we show that the transcription factor FoxO1 regulates adipose transdifferentiation by mediating Tgfß1 signaling pathway. Tgfß1 treatment induced whitening phenotype in beige adipocytes, reducing UCP1 and mitochondrial capacity and enlarging lipid droplets. Deletion of adipose FoxO1 (adO1KO) dampened Tgfß1 signaling by downregulating Tgfbr2 and Smad3 and induced browning of adipose tissue in mice, increasing UCP1 and mitochondrial content and activating metabolic pathways. Silencing FoxO1 also abolished the whitening effect of Tgfß1 on beige adipocytes. The adO1KO mice exhibited a significantly higher energy expenditure, lower fat mass, and smaller adipocytes than the control mice. The browning phenotype in adO1KO mice was associated with an increased iron content in adipose tissue, concurrent with upregulation of proteins that facilitate iron uptake (DMT1 and TfR1) and iron import into mitochondria (Mfrn1). Analysis of hepatic and serum iron along with hepatic iron-regulatory proteins (ferritin and ferroportin) in the adO1KO mice revealed an adipose tissue-liver crosstalk that meets the increased iron requirement for adipose browning. The FoxO1-Tgfß1 signaling cascade also underlay adipose browning induced by ß3-AR agonist CL316243. Our study provides the first evidence of a FoxO1-Tgfß1 axis in the regulation of adipose browning-whitening transdifferentiation and iron influx, which sheds light on the compromised adipose plasticity in conditions of dysregulated FoxO1 and Tgfß1 signaling.


Assuntos
Tecido Adiposo Marrom , Transdiferenciação Celular , Camundongos , Animais , Tecido Adiposo Marrom/metabolismo , Ferro/metabolismo , Obesidade/genética , Obesidade/metabolismo , Transdução de Sinais , Tecido Adiposo Branco/metabolismo , Camundongos Endogâmicos C57BL , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo
16.
J Neurol Sci ; 447: 120608, 2023 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-36906993

RESUMO

Carnosine (ß-alanyl-L-histidine) is a natural dipeptide with multiple neuroprotective properties. Previous studies have advertised that carnosine scavenges free radicals and displays anti-inflammatory activity. However, the underlying mechanism and the efficacies of its pleiotropic effect on prevention remained obscure. In this study, we aimed to investigate the anti-oxidative, anti-inflammative, and anti-pyroptotic effects of carnosine in the transient middle cerebral artery occlusion (tMCAO) mouse model. After a daily pre-treatment of saline or carnosine (1000 mg / kg / day) for 14 days, mice (n = 24) were subjected to tMCAO for 60 min and continuously treated with saline or carnosine for additional 1 and 5 days after reperfusion. The administration of carnosine significantly decreased infarct volume 5 days after the tMCAO (*p < 0.05) and effectively suppressed the expression of 4-HNE, 8-OHdG, Nitrotyrosine 5 days, and RAGE 5 days after tMCAO. Moreover, the expression of IL-1ß was also significantly suppressed 5 days after tMCAO. Our present findings demonstrated that carnosine effectively relieves oxidative stress caused by ischemic stroke and significantly attenuates neuroinflammatory responses related to IL-1ß, suggesting that carnosine can be a promising therapeutic strategy for ischemic stroke.


Assuntos
Carnosina , AVC Isquêmico , Fármacos Neuroprotetores , Acidente Vascular Cerebral , Camundongos , Animais , Carnosina/farmacologia , Carnosina/uso terapêutico , Carnosina/metabolismo , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Estresse Oxidativo , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/tratamento farmacológico , Infarto da Artéria Cerebral Média/metabolismo , AVC Isquêmico/tratamento farmacológico
17.
J Alzheimers Dis ; 2022 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-36565115

RESUMO

BACKGROUND: NADPH oxidase 2 (NOX2) is an important source of reactive oxygen species (ROS). Activated NOX2 may contribute to Alzheimer's disease (AD). Our previous studies showed that a novel vitamin E mixture, Tocovid, had potential neuroprotective effects in a stroke mice model and an AD cell model. OBJECTIVE: The aim of this study was two-fold: to assess whether long-term Tocovid treatment can regulate NOX2, and the therapeutic effects of long-term administration of Tocovid to an AD mice model. METHODS: Therapeutic effects of long-term administration of Tocovid (200 mg/kg /day) on an Aß-overexpressed transgenic AD mice model (APP23, n = 8) was investigated. The therapeutic effect of Tocovid in 16-month-old mice compared with the no-treatment APP23 group (n = 9) was assessed. RESULTS: Tocovid treatment strongly improved motor and memory deficits of APP23 mice by attenuating NOX2 expression, oxidative stress, neuroinflammation, neurovascular unit dysfunction, synaptic alteration, and Aß deposition after 16 months. CONCLUSION: These findings suggest that NOX2 is a potential target in AD pathology. Long-term administration of Tocovid may be a promising candidate for AD treatment.

18.
J Alzheimers Dis ; 86(4): 1973-1982, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35253748

RESUMO

BACKGROUND: The oral ingestion of scallop-derived plasmalogen (sPlas) significantly improved cognitive function in Alzheimer's disease (AD) patients. OBJECTIVE: However, the effects and mechanisms of sPlas on AD with chronic cerebral hypoperfusion (CCH), a class of mixed dementia contributing to 20-30% among the dementia society, were still elusive. METHODS: In the present study, we applied a novel mouse model of AD with CCH to investigate the potential effects of sPlas on AD with CCH. RESULTS: The present study demonstrated that sPlas significantly recovered cerebral blood flow, improved motor and cognitive deficits, reduced amyloid-ß pathology, regulated neuroinflammation, ameliorated neural oxidative stress, and inhibited neuronal loss in AD with CCH mice at 12 M. CONCLUSION: These findings suggest that sPlas possesses clinical and pathological benefits for AD with CCH in the novel model mice. Furthermore, sPlas could have promising prevention and therapeutic effects on patients of AD with CCH.


Assuntos
Doença de Alzheimer , Isquemia Encefálica , Pectinidae , Doença de Alzheimer/patologia , Animais , Encéfalo/patologia , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Humanos , Camundongos , Plasmalogênios/uso terapêutico
19.
J Cereb Blood Flow Metab ; 42(7): 1322-1334, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35130767

RESUMO

The feasibility of transcranial sonothrombolysis has been demonstrated, although little is known about the relationships between thermal or mechanical mechanisms and thrombolytic outcomes. Therefore, the present study aims to reveal the effect and safety of temperature and ultrasound through in vitro and in vivo thrombolysis models. Artificial clots in microtubes were heated in a water bath or sonicated by ultrasound irradiation, and then clots weight decrease with rising temperature and sonication time was confirmed. In the in vitro thrombotic occlusion model, based on spot heating, clot volume was reduced and clots moved to the distal side, followed by recanalization of the occlusion. In the in vivo study, the common carotid artery of rats was exposed to a spot heater or to sonication. No brain infarct or brain blood barrier disruption was shown, but endothelial junctional dysintegrity and an inflammatory response in the carotid artery were detected. The present spot heating and ultrasound irradiation models seem to be effective for disintegrating clots in vitro, but the safety of the in vivo model was not fully supported by the data. However, the data indicates that a shorter time exposure could be less invasive than a longer exposure.


Assuntos
Terapia Trombolítica , Trombose , Terapia por Ultrassom , Animais , Fibrinolíticos/uso terapêutico , Ratos , Trombose/terapia , Ativador de Plasminogênio Tecidual , Terapia por Ultrassom/efeitos adversos
20.
Waste Manag ; 139: 330-340, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-35007953

RESUMO

The environmental risk assessment and the factors influencing heavy metals (HM) in the soil at the municipal solid waste landfill sites (MSWLs) were studied by literature review, field survey, and statistical methods. The results indicated that the dominant HM contamination in the soil at the MSWLs was caused by chromium (Cr) with the Nemero index values (PI) from 22.7 to 44.3 and zinc (Zn) with the PI from 0.7 to 9.8. There were significant differences in the Cr, mercury (Hg), lead (Pb), Zn, and arsenic (As) concentrations between soil samples from sanitary and non-sanitary landfills (NSLs) where HM contamination (PI = 10.9) was more obvious. As (CRAAs = 2.35 × 10-4) and cadmium (Cd) (CRACd = 1.45 × 10-4) posed potential carcinogenic health effects. The soil Cd concentration had a significant negative correlation (r = -0.476**) with the landfill age. The soil As concentration had a significant positive correlation (r = 0.472**) with rainfall in NSLs. There were significant differences in the As (P = 0.042) and copper (Cu) (P = 0.042) concentrations between soil samples from the surrounding areas of MSWLs and the base where soil had higher HM concentrations. For the efficient prevention of HM ecological risk, a scientific site selection, undamaged coverage and anti-seepage systems, standardized management, and ongoing monitoring are required.


Assuntos
Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise , Resíduos Sólidos/análise , Instalações de Eliminação de Resíduos
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