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1.
Front Immunol ; 15: 1450114, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39416782

RESUMO

Introduction: The frequent occurrence of mutations in the SARS-CoV-2 Spike (S) protein, with up to dozens of mutations, poses a severe threat to the current efficacy of authorized COVID-19 vaccines. Membrane (M) protein, which is the most abundant viral structural protein, exhibits a high level of amino acid sequence conservation. M protein ectodomain could be recognized by specific antibodies; however, the extent to which it is immunogenic and provides protection remains unclear. Methods: We designed and synthesized multiple peptides derived from coronavirus M protein ectodomains, and determined the secondary structure of specific peptides using circular dichroism (CD) spectroscopy. Enzyme-linked immunosorbent assay (ELISA) was utilized to detect IgG responses against the synthesized peptides in clinical samples. To evaluate the immunogenicity of peptide vaccines, BALB/c mice were intraperitoneally immunized with peptide-keyhole limpet hemocyanin (KLH) conjugates adjuvanted with incomplete Freund's adjuvant (IFA). The humoral and T-cell immune responses induced by peptide-KLH conjugates were assessed using ELISA and ELISpot assays, respectively. The efficacy of the S2M2-30-KLH vaccine against SARS-CoV-2 variants was evaluated in vivo using the K18-hACE2 transgenic mouse model. The inhibitory effect of mouse immune serum on SARS-CoV-2 virus replication in vitro was evaluated using microneutralization assays. The subcellular localization of the M protein was evaluated using an immunofluorescent staining method, and the Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) activity of the S2M2-30-specific monoclonal antibody (mAb) was measured using an ADCC reporter assay. Results: Seroconversion rates for ectodomain-specific IgG were observed to be high in both SARS-CoV-2 convalescent patients and individuals immunized with inactivated vaccines. To assess the protective efficacy of the M protein ectodomain-based vaccine, we initially identified a highly immunogenic peptide derived from this ectodomain, named S2M2-30. The mouse serum specific to S2M2-30 showed inhibitory effects on the replication of SARS-CoV-2 variants in vitro. Immunizations of K18-hACE2-transgenic mice with the S2M2-30-keyhole limpet hemocyanin (KLH) vaccine significantly reduced the lung viral load caused by B.1.1.7/Alpha (UK) infection. Further mechanism investigations reveal that serum neutralizing activity, specific T-cell response and Fc-mediated antibody-dependent cellular cytotoxicity (ADCC) correlate with the specific immuno-protection conferred by S2M2-30. Discussion: The findings of this study suggest that the antibody responses against M protein ectodomain in the population most likely exert a beneficial effect on preventing various SARS-CoV-2 infections.


Assuntos
Anticorpos Antivirais , COVID-19 , SARS-CoV-2 , Proteínas da Matriz Viral , Replicação Viral , Animais , Feminino , Humanos , Camundongos , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Proteínas M de Coronavírus/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Camundongos Endogâmicos BALB C , SARS-CoV-2/imunologia , Vacinas de Subunidades Antigênicas/imunologia , Proteínas da Matriz Viral/imunologia
2.
J Appl Microbiol ; 2024 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-39394666

RESUMO

AIMS: To develop and evaluate nisin-loaded chitosan/sodium alginate (CS/SA) microspheres as an improved antimicrobial delivery system targeting Staphylococcus aureus strains. METHODS AND RESULTS: The microspheres were prepared using a modified water-in-oil emulsion cross-linking method, resulting in spherical particles sized 1-8 µm with a surface charge of -7.92 ± 5.09 mV, confirmed by scanning electron microscopy (SEM) and Zetasizer analysis. Encapsulation efficiency (EE) and loading capacity (LC) of nisin were 87.60 ± 0.43% and 1.99 ± 0.01%, respectively. In vitro release studies over 48 hours indicated a controlled release pattern of nisin, described by the Korsmeyer-Peppas model, with higher release rates at 37°C and alkaline pH. Antimicrobial assays showed an enhanced efficacy of nisin-loaded CS/SA microspheres compared to free nisin, with minimum inhibitory concentration (MIC) values reduced by 50%. Confocal laser scanning microscopy (CLSM), SEM and transmission electron microscopy (TEM) showed significant bacterial membrane damage and cellular disruption induced by the microspheres. CONCLUSIONS: This study highlights the potential of nisin-loaded CS/SA microspheres as an innovative antimicrobial delivery system with improved stability and antimicrobial efficacy against S. aureus, addressing limitations associated with nisin alone.

3.
IEEE Trans Cybern ; PP2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39405153

RESUMO

The broad learning system (BLS) is a versatile and effective tool for analyzing tabular data. However, the rapid expansion of big data has resulted in an overwhelming amount of tabular data, necessitating the development of specialized tools for effective management and analysis. This article introduces an optimized BLS (OBLS) specifically tailored for big data analysis. In addition, a deep-optimized BLS (DOBLS) network is developed further to enhance the performance and efficiency of the OBLS. The main contributions of this article are: 1) by retracing the network's error from the output space to the latent space, the OBLS adjusts parameters in the feature and enhancement node layers. This process aims to achieve more resilient representations, resulting in improved performance; 2) the DOBLS is a multilayered structure consisting of multiple OBLSs, wherein each OBLS connects to the input and output layers, enabling direct data propagation. This design helps reduce information loss between layers, ensuring an efficient flow of information throughout the network; and 3) the proposed methods demonstrate robustness across various applications, including multiview feature embedding, one-class classification (OCC), camera model identification, electroencephalogram (EEG) signal processing, and radar signal analysis. Experimental results validate the effectiveness of the proposed models. To ensure reproducibility, the source code is available at https://github.com/1027051515/OBLS_DOBLS.

4.
Neural Regen Res ; 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39435629

RESUMO

ABSTRACT: It has been reported that the PI3K/AKT signaling pathway plays a key role In the pathogenesis of ischemic stroke. As a result, the development of drugs targeting the PI3K/AKT signaling pathway has attracted increasing attention from researchers. This article reviews the pathological mechanisms and advancements in research related to the signaling pathways in ischemic stroke, with a focus on the PI3K/AKT signaling pathway.The key findings include the following: (1) The complex pathological mechanisms of ischemic stroke can be categorized into five major types: excitatory amino acid toxicity, Ca2+ overload, inflammatory response, oxidative stress, and apoptosis. (2) The PI3K/AKT-mediated signaling pathway is closely associated with the occurrence and progression of ischemic stroke, which primarily involves the NF-kB, NRF2, BCL-2, mTOR, and endothelial NOS signaling pathways. (3) Natural products, including flavonoids, quinones, alkaloids, phenylpropanoids, phenols, terpenoids, and iridoids, show great potential as candidate substances for the development of innovative anti-stroke medications. (4) Recently, novel therapeutic techniques, such as electroacupuncture and mesenchymal stem cell therapy, have demonstrated the potential to improve stroke outcomes by activating the PI3K/AKT signaling pathway, providing new possibilities for the treatment and rehabilitation of patients with ischemic stroke. Future investigations should focus on the direct regulatory mechanisms of drugs targeting the PI3K/AKT signaling pathway and their clinical translation to develop innovative treatment strategies for ischemic stroke.

5.
Sci Rep ; 14(1): 22345, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39333600

RESUMO

Synergistically improving the strength and toughness of metallic materials is a central focus in the field of physical metallurgy. Yet, there is a noticeable lack of research in strengthening and toughening large-size metal components, whereas those components are extensively used in the modern industry. In this work, a deformation-assisted tempering (DAT) process was proposed to create a novel microstructure in 1.4 tons low-alloyed plain steel. After DAT treatment, the steel contains low dislocation density but high density of low-angle subgrain boundaries and dispersed spherical nano carbides. Such microstructure enables a much better combination of tensile strength and fracture toughness compared to the small-size quench and temper steels. The significant improvement in low-temperature impact toughness is due to the occurrence of delamination and subsequent large plastic deformation at the notch tip. The DAT process can provides a new strategy for the development of large-size fail-safe steel with excellent strength and fracture resistance.

6.
Cardiovasc Diagn Ther ; 14(4): 621-629, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39263480

RESUMO

Background: Recurrent acute myocardial infarction requiring unplanned percutaneous coronary intervention (PCI) is one of the major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS) after PCI. There is a continuing controversy about the association between serum cystatin C, a biomarker for the evaluation of renal function, and the prognosis of ACS patients following PCI. The retrospective study evaluated the association between serum cystatin C level and MACE in ACS patients after PCI. Methods: Data were retrieved for 330 patients with ACS for primary PCI in a single center. Serum cystatin C levels were measured before PCI. All patients underwent regular follow-ups after PCI, and the studied endpoint was MACE, defined as the need for a repeat revascularization in the heart. The predictive value of serum cystatin C for MACE was analyzed using univariate and multivariate analysis. Restricted cubic spline (RCS) analysis was applied to evaluate the dose-response relationship between serum cystatin C level and MACE in ACS patients following PCI. Results: After a median follow-up of 63 months (range, 1-148 months), 121 of the 330 patients experienced MACE. Compared to patients who did not have MACE, patients who had MACE showed a significant decrease in serum cystatin C levels (0.99±0.32 vs. 1.15±0.78 mg/L, P=0.03). In multivariate regression analysis, serum cystatin C level was an independent risk factor for MACE. According to the serum cystatin C level, patients were divided into 4 categories, Cox regression analysis illustrated that the second quartile of serum cystatin C level indicated an increased risk of MACE in patients with PCI for primary ACS compared to the highest quartile [Q2: adjusted hazard ratio (HR) =2.109; 95% confidence interval (CI): 1.193-3.727; P=0.01]. RCS analysis showed a significant U-shaped dose-response relationship between cystatin C level and MACE in patients with PCI for ACS (P for non-linearity =0.004). Conclusions: These results indicated an association between serum cystatin C level and post-PCI MACE in ACS patients.

7.
Int J Nanomedicine ; 19: 8501-8517, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39185344

RESUMO

Background: A successful immune response against tumors depends on various cellular processes. Hence, there is an urgent need to construct a proficient nanoplatform for immunotherapy that can concurrently regulate the activities of various cells participating in the immune process. We have developed zeolitic imidazolate framework-8 (ZIF-8) formula, with good pH sensitivity, which is conducive to the release of drugs in the tumor site (acidic environment) and significantly improves immunotherapy. This is achieved through the coordinated action of different therapeutic agents, such as the photothermal agent polydopamine (PDA), the chemodrug camptothecin (CPT), and the immunomodulator 1-methyl-D-tryptophan (1-MT). Materials and Methods: In this study, we evaluated the antitumor effect of PDA/(CPT + 1-MT) @ZIF-8 (PCMZ) nanoparticles (NPs) in vitro and in vivo and investigated the molecular mechanism of PCMZ NPs in tumor suppression via photothermal-chemo-immunotherapy. Results: MTT and Annexin V-FITC/PI double staining apoptosis test showed that PCMZ NPs could induce apoptosis of 4T1 cell, and PCMZ NPs could cause 4T1 cell necrosis under 808 nm laser irradiation. The objective is to establish a unilateral breast cancer model in mice and investigate the effect of PCMZ NPs on tumor growth and tumor suppression in tumor bearing mice. The results showed that PCMZ NPs showed good heating effect in vivo and effectively inhibited tumor growth under 808 nm laser irradiation. In addition, PCMZ NPs could induce the immunogenic death of tumor cells, promote the maturation of DCs, inhibit IDO pathway, and finally differentiate T cells into cytotoxic T cells and helper T cells, so as to effectively activate the anti-tumor immune response. Conclusion: The PCMZ NPs, possessing good photothermal conversion capabilities due to join of PDA, effectively overcome two main challenges in immunotherapy: insufficient stimulation of the immune response and evasion of the immune system. This provides a robust platform against invasive cancer and recurrent tumors.


Assuntos
Camptotecina , Imunoterapia , Indóis , Camundongos Endogâmicos BALB C , Polímeros , Triptofano , Zeolitas , Animais , Indóis/química , Indóis/farmacologia , Zeolitas/química , Zeolitas/farmacologia , Imunoterapia/métodos , Triptofano/química , Triptofano/farmacologia , Triptofano/análogos & derivados , Camundongos , Concentração de Íons de Hidrogênio , Linhagem Celular Tumoral , Feminino , Polímeros/química , Polímeros/farmacologia , Camptotecina/química , Camptotecina/farmacologia , Nanopartículas/química , Apoptose/efeitos dos fármacos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Humanos , Terapia Fototérmica/métodos , Imidazóis/química , Imidazóis/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Terapia Combinada
8.
J Viral Hepat ; 31(11): 729-738, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39136210

RESUMO

Hepatitis E virus (HEV) is a foodborne zoonotic pathogen that is supposed to be one of the most common causes of acute viral hepatitis. However, HEV infection has been recently associated with a wide spectrum of extrahepatic manifestations, particularly neurological disorders. Previous studies have shown that HEV is able to cross the blood-brain barrier (BBB) and induce inflammatory response of the central nervous system. However, the pathogenesis of HEV-induced neuroinflammation and tissue injury of the central nervous system have yet to be fully elucidated. In this study, activation of NLRP3 inflammasome following HEV infection were investigated. In a gerbil model infected by HEV, brain histopathological changes including gliosis, neuronophagia and neuron injury were observed and expression of NLRP3, caspase-1, IL-1ß and IL-18 were elevated. Brain microvascular endothelial cells (BMECs) are key components of the BBB that protects the brain from various challenges. Following HEV infection, virus-like particles range from 30 to 40 nm in diameter were observed in human BMECs (hBMECs). Enhanced expression levels of NLRP3 and subsequent ASC, caspase-1, IL-1ß and IL-18 were detected in infected cells. Treatment with MCC950 alleviated HEV infection induced activation of NLRP3 inflammasome, mitochondrial damage and VE-cadherin degradation. The findings provide new insights into HEV-associated neuroinflammation. Moreover, targeting NLRP3 inflammasome signalling is a promising therapeutic in HEV-induced neurological disorder.


Assuntos
Encéfalo , Modelos Animais de Doenças , Células Endoteliais , Gerbillinae , Vírus da Hepatite E , Hepatite E , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doenças Neuroinflamatórias , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Inflamassomos/imunologia , Vírus da Hepatite E/imunologia , Vírus da Hepatite E/fisiologia , Doenças Neuroinflamatórias/virologia , Doenças Neuroinflamatórias/patologia , Doenças Neuroinflamatórias/imunologia , Hepatite E/virologia , Hepatite E/patologia , Hepatite E/complicações , Hepatite E/imunologia , Células Endoteliais/virologia , Encéfalo/patologia , Encéfalo/virologia , Humanos , Barreira Hematoencefálica/virologia , Sulfonas/farmacologia , Indenos , Furanos/farmacologia , Sulfonamidas/farmacologia , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Masculino , Interleucina-1beta/metabolismo , Interleucina-18/metabolismo
9.
Mol Neurobiol ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037529

RESUMO

Neuroinflammation has been proven to drive cognitive impairment associated with neurodegenerative diseases. It has been demonstrated that mitochondrial dysfunction is associated with cognitive impairment caused by neuroinflammation. We hypothesized that the transfer of exogenous mitochondria may be beneficial to the therapy of cognitive impairment induced by neuroinflammation. In the study, the effect of exogenous mitochondria on cognitive impairment induced by neuroinflammation was investigated. The results showed that mitochondrial treatment ameliorated the cognitive performance of lipopolysaccharide (LPS)-treated mice. Additionally, mitochondrial therapy attenuated neuronal injury and down-regulated the expression of proinflammatory cytokines, including TNF-α and pro- and cleaved IL-1ß, and the expression of Iba-1 and GFAP in the hippocampus and cortex of LPS-treated mice. Additionally, mitochondrial treatment increased mitochondrial ΔΨm, ATP level, and SOD activity and attenuated MDA level and ROS production in the brains of LPS-treated mice. The study reports the beneficial effect of mitochondrial treatment against cognitive impairment of LPS-treated mice, thereby providing a potential strategy for the treatment of cognitive impairment caused by neuroinflammation.

10.
Chem Commun (Camb) ; 60(42): 5514-5517, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38693792

RESUMO

In this study, we propose a novel therapy system composed of UiO-66 nanoparticles, which contain quercetin combined with chloroquine (UQCNP), to achieve dual autophagy-ubiquitination blockade. Through UiO-66 NP drug loading, the solubility of quercetin (a proteasome inhibitor) was improved under physiological conditions, thereby increasing its effective concentration at the tumor site. The cell experiment results showed that UQCNP significantly increased the apoptosis rate of 4T1 cells by 73.6%, which was significantly higher than other groups. Transmission electron microscopy results showed that the autophagosome of cells in the UQCNP treatment group was significantly lower than that in other treatment groups. Moreover, western blot results showed that, compared with other groups, LC3 expression and proteasome activity (p < 0.01), as well as the tumor volume of mice treated with UQCNP (p < 0.01) were significantly reduced. These results indicate that UQCNP achieves effective tumor therapy by blocking the autophagy and proteasome pathways synchronously.


Assuntos
Autofagia , Cloroquina , Nanopartículas , Quercetina , Ubiquitinação , Quercetina/farmacologia , Quercetina/química , Cloroquina/farmacologia , Cloroquina/química , Animais , Autofagia/efeitos dos fármacos , Camundongos , Nanopartículas/química , Ubiquitinação/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Humanos
11.
Ecotoxicol Environ Saf ; 277: 116331, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38640801

RESUMO

Polystyrene nanoparticles are emerging as contaminants in freshwater environments, posing potential risks to amphibians exposed to extended periods of water contamination. Using tadpoles as a model, this study aimed to evaluate the toxicity of PS NPs. Pyrolysis-gas chromatography-tandem mass spectrometry (Py-GCMS) analysis revealed a concentration-dependent increase in polystyrene nanoparticles (PS NPs) levels in tadpoles with escalating exposure concentrations. Following exposure to 100 nm fluorescent microspheres, fluorescence was observed in the intestines and gills, peaking at 48 hours. Histopathological analysis identified degenerative necrosis and inflammation in the liver, along with atrophic necrosis of glomeruli and tubules in the kidneys. These results indicate a discernible impact of PS NPs on antioxidant levels, including reduced superoxide dismutase and catalase activities, elevated glutathione content, and increased malondialdehyde levels. Electron microscopy observations revealed the infiltration of PS NPs into Kupffer's cells and hepatocytes, leading to visible lesions such as nuclear condensation and mitochondrial disruption. The primary objective of this research was to elucidate the adverse effects of prolonged PS NPs exposure on amphibians.


Assuntos
Larva , Fígado , Nanopartículas , Estresse Oxidativo , Poliestirenos , Poluentes Químicos da Água , Animais , Poliestirenos/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Nanopartículas/toxicidade , Fígado/efeitos dos fármacos , Fígado/patologia , Poluentes Químicos da Água/toxicidade , Larva/efeitos dos fármacos , Glutationa/metabolismo , Superóxido Dismutase/metabolismo , Malondialdeído/metabolismo , Catalase/metabolismo
12.
Int J Nanomedicine ; 19: 2995-3007, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38559446

RESUMO

Background: In the past decades, antimicrobial resistance (AMR) has been a major threat to global public health. Long-term, chronic otitis media is becoming more challenging to treat, thus the novel antibiotic alternative agents are much needed. Methods: ZnO@TiO2@AMP (ATZ NPs) were synthesized through a solvothermal method and subjected to comprehensive characterization. The in vitro and in vivo antibacterial effect and biocompatibility of ATZ NPs were evaluated. For the antibacterial mechanism exploration, we utilized the Electron Paramagnetic Resonance (EPR) Spectrometer to detect and analyze the hydroxyl radicals produced by ATZ NPs. Results: ATZ NPs exhibited a spherical structure of 99.85 nm, the drug-loading rate for ZnO was 20.73%, and AMP within ATZ NPs was 41.86%. Notably, the Minimum Inhibitory Concentration (MIC) value of ATZ NPs against Staphylococcus aureus (S. aureus), methicillin-resistant Staphylococcus aureus (MRSA), and Streptococcus pneumoniae (S. pneumoniae) were 10 µg/mL, and Minimum Bactericidal Concentration (MBC) value of ATZ NPs against S. aureus, and S. pneumoniae were 50 µg/mL. In comparison to the model group, the treatment of otitis media with ATZ NPs significantly reduces inflammatory exudation in the middle ear cavity, with no observable damage to the tympanic membrane. Both in vivo and in vitro toxicity tests indicating the good biocompatibility of ATZ NPs. Moreover, EPR spectroscopy results highlighted the superior ability of ATZ NPs to generate hydroxyl radicals (·OH) compared to ZnO NPs. Conclusion: ATZ NPs exhibited remarkable antibacterial properties both in vivo and in vitro. This innovative application of advanced ATZ NPs, bringing great promise for the treatment of otitis media.


Assuntos
Nanopartículas Metálicas , Staphylococcus aureus Resistente à Meticilina , Otite Média , Infecções Estafilocócicas , Óxido de Zinco , Humanos , Staphylococcus aureus , Radical Hidroxila , Óxido de Zinco/farmacologia , Óxido de Zinco/química , Antibacterianos/farmacologia , Antibacterianos/química , Otite Média/tratamento farmacológico , Testes de Sensibilidade Microbiana , Nanopartículas Metálicas/química
13.
Sci Total Environ ; 924: 171637, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38479528

RESUMO

Wastewater treatment plants (WWTPs) have been regarded as the main sources of greenhouse gas (GHG) emissions. This study compares the influent characteristics of industrial wastewater represented by the WWTP of paper mill and that of domestic sewage represented by the Benchmark Simulation Model No. 1 (BSM1) under stormy weather. The various sources of GHG emissions from the two processes are calculated, and the contribution of each source to the total GHG emissions is assessed. Firstly, based on the mass balance analysis and the recognized emission factors, a GHG emission calculation model was established for the on-site and off-site GHG emission sources from the WWTP of paper mill. Simultaneously, a GHG emission experimental model was established by determining the dissolved concentrations of carbon dioxide (CO2) and nitrous oxide (N2O) in the papermaking wastewater, to verify the accuracy of the developed GHG calculation model. Subsequently, an optimum aeration rate for the paper mill was investigated to comply with the discharging norms. Under the optimum aeration rate of 10 h-1, the obtained calculation accuracies of CO2 and N2O emissions were 94.6 % and 91.1 %, respectively. The mean total GHG emission in the WWTP of paper mill was 550 kg CO2-eq·h-1, of which 44.6 % came from the on-site emission sources and 55.4 % from the off-site emission sources. It was also uncovered that the electrical consumption for aeration was the largest contributor to the total GHG emissions with a proportion of 25.2 %, revealing that the control strategy of the aeration rate is highly significant in reducing GHG emissions in WWTP of paper mills.

15.
J Nanobiotechnology ; 22(1): 99, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461229

RESUMO

The Influenza A virus (IAV) is a zoonotic pathogen that infects humans and various animal species. Infection with IAV can cause fever, anorexia, and dyspnea and is often accompanied by pneumonia characterized by an excessive release of cytokines (i.e., cytokine storm). Nanodrug delivery systems and nanoparticles are a novel approach to address IAV infections. Herein, UiO-66 nanoparticles (NPs) are synthesized using a high-temperature melting reaction. The in vitro and in vivo optimal concentrations of UiO-66 NPs for antiviral activity are 200 µg mL-1 and 60 mg kg-1, respectively. Transcriptome analysis revealed that UiO-66 NPs can activate the RIG-I-like receptor signaling pathway, thereby enhancing the downstream type I interferon antiviral effect. These NPs suppress inflammation-related pathways, including the FOXO, HIF, and AMPK signaling pathways. The inhibitory effect of UiO-66 NPs on the adsorption and entry of IAV into A549 cells is significant. This study presents novel findings that demonstrate the effective inhibition of IAV adsorption and entry into cells via UiO-66 NPs and highlights their ability to activate the cellular RIG-I-like receptor signaling pathway, thereby exerting an anti-IAV effect in vitro or in mice. These results provide valuable insights into the mechanism of action of UiO-66 NPs against IAV and substantial data for advancing innovative antiviral nanomedicine.


Assuntos
Vírus da Influenza A , Influenza Humana , Estruturas Metalorgânicas , Infecções por Orthomyxoviridae , Ácidos Ftálicos , Camundongos , Humanos , Animais , Infecções por Orthomyxoviridae/tratamento farmacológico , Transdução de Sinais , Antivirais/farmacologia , Antivirais/uso terapêutico
16.
J Neurointerv Surg ; 2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38124230

RESUMO

BACKGROUND: Recently, a randomized controlled trial showed a beneficial effect of intra-arterial thrombolysis following successful endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large vessel occlusion in the anterior circulation. Due to differences in response to thrombolytics in occlusion of the posterior circulation, the purpose of ATTENTION IA is to explore the adjunct benefit of intra-arterial thrombolysis after successful recanalization in patients presenting with large and medium vessel occlusion of the posterior circulation. METHODS: ATTENTION-IA is an investigator-initiated, multicenter, prospective, randomized clinical trial with open-label treatment and blinded endpoint assessment (PROBE). After achieving successful recanalization (expanded Thrombolysis In Cerebral Infarction (eTICI) 2b-3) of an occlusion of the vertebral, basilar, or posterior cerebral artery, patients will be randomized 1:1 to receive intra-arterial tenecteplase or standard of care. The primary effect parameter is a modified Rankin Score of 0-1 at day 90. RESULTS: The trial recently completed enrollment, and data collection/verification is ongoing. The final results will be made available on completion of enrollment and follow-up. CONCLUSIONS: ATTENTION-IA will provide definitive evidence for the efficacy and safety of adjunct intra-arterial tenecteplase after successful EVT in patients with an acute posterior circulation arterial occlusion stroke presenting within 24 hours of symptom onset. TRIAL REGISTRATION: ClinicalTrials.gov NCT05684172.

17.
Emerg Microbes Infect ; 12(2): 2276336, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37882369

RESUMO

Hepatitis E virus (HEV) has become one of the important pathogens that threaten the global public health. Type 3 and 4 HEV are zoonotic, which can spread vertically and cause placental damage. At the same time, autophagy plays an important role in the process of embryo development and pregnancy maintenance. However, the relationship between HEV and autophagy, especially in the placenta tissue, has not been clarified. We found lower litter rates in HEV-infected female mice, with significant intrauterine abortion of the embryo (24.19%). To explore the effects of HEV infection on placenta autophagy, chorionic cells (JEG-3) and mice placenta have been employed as research objects, while the expression of autophagy-related proteins (ATGs) has been detected in JEG-3 cells with different times of HEV inoculation. The results demonstrated that the expression of protein LC3 decreased and p62 accumulated, meanwhile ATGs such as ATG4B, ATG5, and ATG9A in JEG-3 cells have decreased significantly. In addition, the maturation of autophagosomes, which referred to the process of the combination of autophagosomes and lysosomes was prevented by HEV infection as well. All processes of autophagic flux, which include the initiation, development, and maturation three stages, were suppressed in JEG-3 cells after HEV infection. Similarly, the protein and gene expression of LC3 were significantly decreased in the placenta of pregnant mice with HEV infection. In summary, our results suggested that HEV inhibited autophagy in JEG-3 cells and placenta of pregnant mice, which might be the important pathogenic mechanisms of HEV infection leading to embryo abortion.


Assuntos
Vírus da Hepatite E , Hepatite E , Gravidez , Feminino , Animais , Camundongos , Placenta , Trofoblastos/metabolismo , Vírus da Hepatite E/genética , Linhagem Celular Tumoral , Autofagia/fisiologia
18.
J Stroke ; 25(3): 399-408, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37607695

RESUMO

BACKGROUND AND PURPOSE: To examine the clinical and safety outcomes after endovascular treatment (EVT) for acute basilar artery occlusion (BAO) with different anesthetic modalities. METHODS: This was a retrospective analysis using data from the Endovascular Treatment for Acute Basilar Artery Occlusion (ATTENTION) registry. Patients were divided into two groups defined by anesthetic modality performed during EVT: general anesthesia (GA) or non-general anesthesia (non-GA). The association between anesthetic management and clinical outcomes was evaluated in a propensity score matched (PSM) cohort and an inverse probability of treatment weighting (IPTW) cohort to adjust for imbalances between the two groups. RESULTS: Our analytic sample included 1,672 patients from 48 centers. The anesthetic modality was GA in 769 (46.0%) and non-GA in 903 (54.0%) patients. In our primary analysis with the PSM-based cohort, non-GA was comparable to GA concerning the primary outcome (adjusted common odds ratio [acOR], 1.01; 95% confidence interval [CI], 0.82 to 1.25; P=0.91). Mortality at 90 days was 38.4% in the GA group and 35.8% in the non-GA group (adjusted risk ratio, 0.95; 95% CI, 0.83 to 1.08; P=0.44). In our secondary analysis with the IPTW-based cohort, the anesthetic modality was significantly associated with the distribution of modified Rankin Scale at 90 days (acOR: 1.45 [95% CI: 1.20 to 1.75]). CONCLUSION: In this nationally-representative observational study, acute ischemic stroke patients due to BAO undergoing EVT without GA had similar clinical and safety outcomes compared with patients treated with GA. These findings provide the basis for large-scale randomized controlled trials to test whether anesthetic management provides meaningful clinical effects for patients undergoing EVT.

19.
Phytother Res ; 37(12): 5509-5528, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37641491

RESUMO

The pathogenesis of ischemic stroke is complex, and PI3K/Akt signaling is considered to play a crucial role in it. The PI3K/Akt pathway regulates inflammation, oxidative stress, apoptosis, autophagy, and vascular endothelial homeostasis after cerebral ischemia; therefore, drug research targeting the PI3K/Akt pathway has become the focus of scientists. In this review, we analyzed the research reports of antiischemic stroke drugs targeting the PI3K/Akt pathway in the past two decades. Because of the rich sources of natural products, increasing studies have explored the value of natural compounds, including Flavonoids, Quinones, Alkaloids, Phenylpropanoids, Phenols, Saponins, and Terpenoids, in alleviating neurological impairment and achieved satisfactory results. Herbal extracts and medicinal formulas have been applied in the treatment of ischemic stroke for thousands of years in East Asian countries. These precious clinical experiences provide a new avenue for research of antiischemic stroke drugs. Finally, we summarize and discuss the characteristics and shortcomings of the current research and put forward prospects for further in-depth exploration.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , AVC Isquêmico/tratamento farmacológico , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/patologia , Fitoterapia
20.
Artigo em Inglês | MEDLINE | ID: mdl-37362100

RESUMO

Shudage-4, an ancient and well-known formula in traditional Mongolian medicine comprising four different types of traditional Chinese medicine, is widely used in the treatment of gastric ulcers. However, the potential material basis and molecular mechanism of Shudage-4 in attenuating stress-induced gastric ulcers remain unclear. This study aimed to first explore the potential material basis and molecular mechanism of Shudage-4 in attenuating gastric ulcers in rats. The chemical constituents and transitional components in the blood of Shudage-4 were identified by ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS). The rat gastric ulcer model was induced by water immersion restraint stress (WIRS). The ulcer damage to gastric tissue was measured at the gross anatomical level and pathological level by hematoxylin-eosin (HE) staining of gastric tissue. RNA sequencing of gastric tissue and plasma metabolomics were performed to analyze the mechanism of Shudage-4 against gastric ulcers. A Pearson correlation analysis was performed to explore the association between serum metabolites and gene expression of gastric tissue. A total of 30 chemical constituents were identified in Shudage-4 by UPLC-TOF-MS. Among 30 constituents, 13 transitional components in the blood were considered as the potential material basis. Shudage-4 treatment had a significant effect on WIRS-induced gastric ulcers in rats. HE staining of gastric tissue illustrated that WIRS-induced ulcer damage was suppressed by Shudage-4 treatment. RNA sequencing of gastric tissue showed that 282 reversed expression genes in gastric tissue were related to Shudage-4 treatment, and gene set enrichment analysis revealed that Shudage-4 treatment significantly inhibited gene set expression related to reactive oxygen species (ROS), which was also validated by detecting rat gastric tissue MDA, GSH, SOD, GSH-Px, and CAT activities. The plasma metabolomic data demonstrated that 23 significantly differential metabolites were closely associated with the Shudage-4 treatment. The further multiomics joint analysis found that significantly upregulated 5 plasma metabolites in Shudage-4-treated rats compared to model rats were negatively correlated with gene set expression related to ROS in gastric tissue. Shudage-4 alleviated WIRS-induced gastric ulcers by inhibiting ROS generation, which was achieved by regulating plasma metabolites level.

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