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1.
Crit Care ; 28(1): 213, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956604

RESUMO

BACKGROUND: The multidimensional biological mechanisms underpinning acute respiratory distress syndrome (ARDS) continue to be elucidated, and early biomarkers for predicting ARDS prognosis are yet to be identified. METHODS: We conducted a multicenter observational study, profiling the 4D-DIA proteomics and global metabolomics of serum samples collected from patients at the initial stage of ARDS, alongside samples from both disease control and healthy control groups. We identified 28-day prognosis biomarkers of ARDS in the discovery cohort using the LASSO method, fold change analysis, and the Boruta algorithm. The candidate biomarkers were validated through parallel reaction monitoring (PRM) targeted mass spectrometry in an external validation cohort. Machine learning models were applied to explore the biomarkers of ARDS prognosis. RESULTS: In the discovery cohort, comprising 130 adult ARDS patients (mean age 72.5, 74.6% male), 33 disease controls, and 33 healthy controls, distinct proteomic and metabolic signatures were identified to differentiate ARDS from both control groups. Pathway analysis highlighted the upregulated sphingolipid signaling pathway as a key contributor to the pathological mechanisms underlying ARDS. MAP2K1 emerged as the hub protein, facilitating interactions with various biological functions within this pathway. Additionally, the metabolite sphingosine 1-phosphate (S1P) was closely associated with ARDS and its prognosis. Our research further highlights essential pathways contributing to the deceased ARDS, such as the downregulation of hematopoietic cell lineage and calcium signaling pathways, contrasted with the upregulation of the unfolded protein response and glycolysis. In particular, GAPDH and ENO1, critical enzymes in glycolysis, showed the highest interaction degree in the protein-protein interaction network of ARDS. In the discovery cohort, a panel of 36 proteins was identified as candidate biomarkers, with 8 proteins (VCAM1, LDHB, MSN, FLG2, TAGLN2, LMNA, MBL2, and LBP) demonstrating significant consistency in an independent validation cohort of 183 patients (mean age 72.6 years, 73.2% male), confirmed by PRM assay. The protein-based model exhibited superior predictive accuracy compared to the clinical model in both the discovery cohort (AUC: 0.893 vs. 0.784; Delong test, P < 0.001) and the validation cohort (AUC: 0.802 vs. 0.738; Delong test, P = 0.008). INTERPRETATION: Our multi-omics study demonstrated the potential biological mechanism and therapy targets in ARDS. This study unveiled several novel predictive biomarkers and established a validated prediction model for the poor prognosis of ARDS, offering valuable insights into the prognosis of individuals with ARDS.


Assuntos
Biomarcadores , Síndrome do Desconforto Respiratório , Humanos , Síndrome do Desconforto Respiratório/sangue , Masculino , Feminino , Idoso , Biomarcadores/sangue , Biomarcadores/análise , Prognóstico , Pessoa de Meia-Idade , Proteômica/métodos , Estudos de Coortes , Idoso de 80 Anos ou mais , Proteínas Sanguíneas/análise , Metabolômica/métodos , Multiômica
2.
Int J Biol Macromol ; 275(Pt 2): 133493, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960230

RESUMO

Cotton has attracted considerable attention due to its functional characteristics. The focus of research on cotton has shifted in recent years towards designing multi-functional and modified media for cotton fibers, which can be firmly combined with textiles, giving them reusability and extending their service life. This study constructed a synergistic antibacterial layer of quaternary ammonium compounds (QACs) and N-halamine (Hals) using an in-situ free radical copolymerization method in water, named QACs/Hals@cotton-Cl. The route significantly increases the number of antibacterial active centers. FTIR, XPS, and SEM were used to systematically analyze the product's chemical structure, surface morphology, and other characteristics. The modified fabric's antibacterial efficiency, wound healing, renewability, and durability were also evaluated. The chlorinated modified cotton fabric could completely eradicate S. aureus and E. coli within 10 min. Compared with pure cotton, it notably promoted the healing rate of infected wounds in mice. The modification method imparted excellent hydrophobicity to the cotton fabric, with a contact angle exceeding 130°, making it easy to remove surface stains. After 30 days of regular storage and 24 h of UV irradiation, the active chlorine concentration (Cl+%) only decreased by 25 % and 39 %, respectively, and the reduced Cl+% was effectively recharged via simple re-chlorination. The hydrophobicity and antimicrobial properties of QACs/Hals@cotton-Cl remained stable even after 20 cycles of friction. This simple synthesis technique provides a convenient approach for the scalable fabrication of multifunctional and rechargeable antibacterial textiles, with potential applications in medical devices and personal hygiene protection.

3.
Sensors (Basel) ; 24(13)2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-39001146

RESUMO

This study develops a model to assess building vulnerability across Xinxing County by integrating quantitative derivation with machine learning techniques. Building vulnerability is characterized as a function of landslide hazard risk and building resistance, wherein landslide hazard risk is derived using CNN (1D) for nine hazard-causing factors (elevation, slope, slope shape, geotechnical body type, geological structure, vegetation cover, watershed, and land-use type) and landslide sites; building resistance is determined through quantitative derivation. After evaluating the building susceptibility of all the structures, the susceptibility of each village is then calculated through subvillage statistics, which are aimed at identifying the specific needs of each area. Simultaneously, different landslide hazard classes are categorized, and an analysis of the correlation between building resistance and susceptibility reveals that building susceptibility exhibits a positive correlation with landslide hazard and a negative correlation with building resistance. Following a comprehensive assessment of building susceptibility in Xinxing County, a sample encompassing different landslide intensity areas and susceptibility classes of buildings was chosen for on-site validation, thus yielding an accuracy rate of the results as high as 94.5%.

4.
Bioresour Technol ; 407: 131096, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38986881

RESUMO

In this study, a microbial fuel cell was constructed using Raoultella sp. XY-1 to efficiently degrade tetracycline (TC) and assess the effectiveness of the electrochemical system. The degradation rate reached 83.2 ± 1.8 % during the 7-day period, in which the system contained 30 mg/L TC, and the degradation pathway and intermediates were identified. Low concentrations of TC enhanced anodic biofilm power production, while high concentrations of TC decreased the electrochemical activity of the biofilm, extracellular polymeric substances, and enzymatic activities associated with electron transfer. Introducing electrogenic bacteria improved power generation efficiency. A three-strain hybrid system was fabricated using Castellaniella sp. A3, Castellaniella sp. A5 and Raoultella sp. XY-1, leading to the enhanced TC degradation rate of 90.4 % and the increased maximum output voltage from 200 to 265 mV. This study presents a strategy utilizing tetracycline-degrading bacteria as bioanodes for TC removal, while incorporating electrogenic bacteria to enhance electricity generation.

5.
QJM ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38924510

RESUMO

BACKGROUND: There are currently three strategies for the duration of LMWH lead-in before DOACs in patients with acute PE: one is at least 5 days, the other is at least 3 days, and the last one is less than 3 days. Which one is the best is yet unknown. METHODS: We divided non-high-risk PE patients into short-LMWH (LMWH <3 days), intermediate-LMWH (LMWH 3-5 days), and long-LMWH (LMWH >5 days) groups, in a 1:1:2 ratio by using propensity score matching. Primary outcomes were a composite of mortality including all-cause and PE-related mortality, VTE recurrence, and major bleeding, as well as each one of them, at 3-month after PE diagnosis. RESULTS: The short-LMWH group (N = 504) had higher 3-month composite primary outcome (129 [25.6%] vs 67 [13.3%], P < 0.001), all-cause mortality (112 [22.2%] vs 39 [7.7%], P < 0.001), and PE-related mortality (48 [9.5%] vs 17 [3.4%], P < 0.001), than the intermediate-LMWH group (N = 504). The short-LMWH group also had higher 3-month composite primary outcome (129 [25.6%] vs 151 [15.0%], P < 0.001), all-cause mortality (112 [22.2%] vs 90 [8.9%], P < 0.001), and PE-related mortality (48 [9.5%] vs 41 [4.1%], P < 0.001) than the long-LMWH group (N = 1008). The VTE recurrence and major bleeding rates were similar between the short-LMWH and intermediate-LMWH groups, and between the short-LMWH and long-LMWH groups. The intermediate-LMWH and long-LMWH groups had similar 3-month primary outcomes rates in whole or in part with each other. CONCLUSIONS: For patients with non-high-risk acute PE, the optimal duration of initial LMWH lead-in before switching to DOACs could be 3 to 5 days.

7.
Nat Commun ; 15(1): 4505, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802413

RESUMO

Avian influenza A virus H7N9 causes severe human infections with >30% fatality. Currently, there is no H7N9-specific prevention or treatment for humans. Here, from a 2013 H7N9 convalescent case in Hong Kong, we isolate four hemagglutinin (HA)-reactive monoclonal antibodies (mAbs), with three directed to the globular head domain (HA1) and one to the stalk domain (HA2). Two clonally related HA1-directed mAbs, H7.HK1 and H7.HK2, potently neutralize H7N9 and protect female mice from lethal H7N9/AH1 challenge. Cryo-EM structures reveal that H7.HK1 and H7.HK2 bind to a ß14-centered surface and disrupt the 220-loop that makes hydrophobic contacts with sialic acid on an adjacent protomer, thereby blocking viral entry. Sequence analysis indicates the lateral patch targeted by H7.HK1 and H7.HK2 to be conserved among influenza subtypes. Both H7.HK1 and H7.HK2 retain HA1 binding and neutralization capacity to later H7N9 isolates from 2016-2017, consistent with structural data showing that the antigenic mutations during this timeframe occur at their epitope peripheries. The HA2-directed mAb H7.HK4 lacks neutralizing activity but when used in combination with H7.HK2 moderately augments female mouse protection. Overall, our data reveal antibodies to a conserved lateral HA1 supersite that confer neutralization, and when combined with a HA2-directed non-neutralizing mAb, augment protection.


Assuntos
Anticorpos Monoclonais , Anticorpos Neutralizantes , Anticorpos Antivirais , Glicoproteínas de Hemaglutininação de Vírus da Influenza , Subtipo H7N9 do Vírus da Influenza A , Influenza Humana , Subtipo H7N9 do Vírus da Influenza A/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Humanos , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Feminino , Influenza Humana/imunologia , Influenza Humana/virologia , Influenza Humana/prevenção & controle , Camundongos , Anticorpos Antivirais/imunologia , Anticorpos Monoclonais/imunologia , Camundongos Endogâmicos BALB C , Microscopia Crioeletrônica , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/virologia , Epitopos/imunologia
8.
Int J Infect Dis ; 146: 107120, 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38821186

RESUMO

OBJECTIVES: Non-tuberculous mycobacteria (NTM) frequently colonize the airways of patients with bronchiectasis; however, there has been limited research into airway microbiota composition and predisposing factors for NTM detection during acute bronchiectasis exacerbations. METHODS: This study enrolled 34 patients with bronchiectasis experiencing acute exacerbations. Metagenomic next-generation sequencing was used to detect microbiota in bronchoalveolar lavage fluid (BALF), and bioinformatics methods were used for the comparative analysis of meaningful microbiota in the BALF of patients with acute exacerbations of bronchiectasis. A correlation analysis was conducted to identify susceptibility factors for NTM in patients with bronchiectasis. RESULTS: Compared with patients with community-acquired pneumonia, patients with bronchiectasis had higher detection rates of NTM (38.2%), Pseudomonas aeruginosa, and Haemophilus influenzae. Patients with NTM-positive bronchiectasis had lower body mass index and lipid profiles than patients who were NTM-negative. Metagenomic next-generation sequencing of BALF revealed patients who were NTM-positive had increased relative abundance of Rothia and other anaerobic genera compared with patients who were NTM-negative. Patients who were NTM-positive also showed higher levels of Streptococcus parasanguinis at the species level. Elevated Rothia mucilaginosa and S. parasanguinis correlated with decreased percentages of clusters of differentiation 3+ T lymphocytes and clusters of differentiation 3+ T-cell subgroups in peripheral blood. CONCLUSIONS: NTM colonization increases the risk of acute bronchiectasis exacerbations. Low body mass index, lipid levels, and isolation of R. mucilaginosa and S. parasanguinis in BALF are susceptibility factors for NTM colonization in patients with bronchiectasis.

9.
Front Med (Lausanne) ; 11: 1338947, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633306

RESUMO

Background: Interstitial lung disease (ILD) is a common complication of idiopathic inflammatory myopathy (IIM), which is one of the connective tissue diseases (CTD). It can lead to poor prognosis and increased mortality. However, the distribution and role of the lower respiratory tract (LRT) microbiome in patients with IIM-ILD remains unclear. This study aimed to investigate the microbial diversity and community differences in bronchoalveolar lavage fluid (BALF) in patients with IIM-ILD. Methods: From 28 June 2021 to 26 December 2023, 51 individual BALF samples were enrolled, consisting of 20 patients with IIM-ILD, 16 patients with other CTD-ILD (including 8 patients with SLE and 8 with RA) and 15 patients with CAP. The structure and function of microbiota in BALF were identified by metagenomic next-generation sequencing (mNGS). Results: The community evenness of LRT microbiota within the IIM-ILD group was marginally lower compared to the other CTD-ILD and CAP groups. Nonetheless, there were no noticeable differences. The species community structure was similar among the three groups, based on the Bray-Curtis distance between the samples. At the level of genus, the IIM-ILD group displayed a considerably higher abundance of Pseudomonas and Corynebacterium in comparison to the CAP group (p < 0.01, p < 0.05). At the species level, we found that the relative abundance of Pseudomonas aeruginosa increased significantly in the IIM-ILD group compared to the CAP group (p < 0.05). Additionally, the relative abundance of Prevotella pallens was significantly higher in other CTD-ILD groups compared to that in the IIM-ILD group (p < 0.05). Of all the clinical indicators examined in the correlation analysis, ferritin level demonstrated the strongest association with LRT flora, followed by Serum interleukin-6 level (p < 0.05). Conclusion: Our research has identified particular LRT microorganisms that were found to be altered in the IIM-ILD group and were significantly associated with immune function and inflammatory markers in patients. The lower respiratory tract microbiota has potential in the diagnosis and treatment of IIM-ILD.

10.
Microorganisms ; 12(3)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38543636

RESUMO

Vermiculite is a clay mineral with unique physical properties that plays a significant role in plant cultivation, soil remediation, and solid waste management. In this research, we first explored how vermiculite-to-microbe interactions evolved during sludge-waste mushroom residue co-composting. Vermiculite's addition had a substantial impact on the microbial α and ß diversities, significantly changed the microbial community pattern, and strengthened the composting nutrient circulation through the formation of more specialist and generalist species. The microbial community characteristics exhibited common co-networks for resisting composting environment stresses. Vermiculite contributed to enhancing the keystone taxa Proteobacteria and Actinobacteriota and caused the ecological function network to diversify in the warming and maturation phases, with more complexity and tightness in the thermophilic phase (with super-generalist species existing). The enhanced microbial interactions induced by vermiculite possessed a greater capacity to facilitate the metabolisms of carbohydrates and amino acids and cellulolysis, thereby promoting composting humification, and nitrogen retention in the final compost and composting maturity. These findings are helpful for us to understand the biological process mechanisms of the effect of vermiculite additives on composting and contribute to the establishment of a theoretical framework for enhancing the microbial interactions in composting systems by adding vermiculite in practical applications.

11.
BMC Oral Health ; 24(1): 213, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341576

RESUMO

BACKGROUND: During dental procedures, critical parameters, such as cooling condition, speed of the rotary dental turbine (handpiece), and distance and angle from pollution sources, were evaluated for transmission risk of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), simulated by spiking in a plasmid encoding a modified viral spike protein, HexaPro (S6P), in droplets and aerosols. METHODS: To simulate routine operation in dental clinics, dental procedures were conducted on a dental manikin within a digital dental unit, incorporating different dental handpiece speeds and cooling conditions. The tooth model was immersed in Coomassie brilliant blue dye and was pre-coated with 100 µL water spiked-in with S6P-encoding plasmid. Furthermore, the manikin was surrounded by filter papers and Petri dishes positioned at different distances and angles. Subsequently, the filter papers and Petri dishes were collected to evaluate the aerosol splash points and the viral load of S6P-encoding plasmid in aerosols and splatters generated during the dental procedure. RESULTS: Aerosol splashing generated a localized pollution area extended up to 60 cm, with heightened contamination risks concentrated within a 30 cm radius. Significant differences in aerosol splash points and viral load by different turbine handpiece speeds under any cooling condition (P < 0.05) were detected. The highest level of aerosol splash points and viral load were observed when the handpiece speed was set at 40,000 rpm. Conversely, the lowest level of aerosol splash point and viral load were found at a handpiece speed of 10,000 rpm. Moreover, the aerosol splash points with higher viral load were more prominent in the positions of the operator and assistant compared to other positions. Additionally, the position of the operator exhibited the highest viral load among all positions. CONCLUSIONS: To minimize the spread of aerosol and virus in clinics, dentists are supposed to adopt the minimal viable speed of a dental handpiece with limited cooling water during dental procedures. In addition, comprehensive personal protective equipment is necessary for both dental providers and dental assistants.


Assuntos
Aerossóis e Gotículas Respiratórios , SARS-CoV-2 , Humanos , Modelos Dentários , Aerossóis , Água
12.
Bioresour Technol ; 393: 130133, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38043689

RESUMO

Heavy metal-resistant bacteria secrete extracellular proteins (e-PNs). However, the role of e-PNs in heavy metal resistance remains elusive. Here Fourier Transform Infrared Spectroscopy implied that N-H, C = O and NH2-R played a crucial role in the adsorption and resistance of Ni2+ in the model organism Cuprividus pauculus 1490 (C. pauculus). Proteinase K treatment reduced Ni2+ resistance of C. pauculus underlining the essential role of e-PNs. Further three-dimension excitation-emission matrix fluorescence spectroscopy analysis demonstrated that tryptophan proteins as part of the e-PNs increased significantly with Ni2+ treatment. Proteomic and quantitative real-time polymerase chain reaction data indicated that major changes were induced in the metabolism of C. pauculus in response to Ni2+. Among those lipopolysaccharide biosynthesis, general secretion pathways, Ni2+-affiliated transporters and multidrug efflux play an essential role in Ni2+ resistance. Altogether the results provide a conceptual model for comprehending how e-PNs contribute to bacterial resistance and adsorption of Ni2+.


Assuntos
Cupriavidus , Metais Pesados , Níquel , Proteômica , Metais Pesados/metabolismo , Cupriavidus/metabolismo
13.
Res Sq ; 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37986867

RESUMO

The avian influenza A virus H7N9 causes severe human infections with more than 30% fatality despite the use of neuraminidase inhibitors. Currently there is no H7N9-specific prevention or treatment for humans. From a 2013 H7N9 convalescent case occurred in Hong Kong, we isolated four H7 hemagglutinin (HA)-reactive monoclonal antibodies (mAbs) by single B cell cloning, with three mAbs directed to the HA globular head domain (HA1) and one to the HA stem region (HA2). Two clonally related HA1-directed mAbs, H7.HK1 and H7.HK2, potently neutralized H7N9 and protected mice from a lethal H7N9/AH1 challenge. Cryo-EM structures revealed that H7.HK1 and H7.HK2 bind to a ß14-centered surface partially overlapping with the antigenic site D of HA1 and disrupt the 220-loop that makes hydrophobic contacts with sialic acid on the adjacent protomer, thus affectively blocking viral entry. The more potent mAb H7.HK2 retained full HA1 binding and neutralization capacity to later H7N9 isolates from 2016-2017, which is consistent with structural data showing that the antigenic mutations of 2016-2017 from the 2013 H7N9 only occurred at the periphery of the mAb epitope. The HA2-directed mAb H7.HK4 lacked neutralizing activity but protected mice from the lethal H7N9/AH1 challenge when engineered to mouse IgG2a enabling Fc effector function in mice. Used in combination with H7.HK2 at a suboptimal dose, H7.HK4 augmented mouse protection. Our data demonstrated an allosteric mechanism of mAb neutralization and augmented protection against H7N9 when a HA1-directed neutralizing mAb and a HA2-directed non-neutralizing mAb were combined.

14.
Emerg Microbes Infect ; 12(2): 2261559, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37732336

RESUMO

Limited follow-up data is available on the recovery of Omicron COVID-19 patients after acute illness. It is also critical to understand persistence of neutralizing antibody (NAb) and of T-cell mediated immunity and the role of hybrid immunity in preventing SARS-CoV-2 reinfection. This prospective cohort study included Omicron COVID-19 individuals from April to June 2022 in Shanghai, China, during a large epidemic caused by the Omicron BA.2 variant. A total of 8945 patients from three medical centres were included in the follow up programme from November 2022 to February 2023. Of 6412 individuals enrolled for the long COVID analysis, 605 (9.4%) individuals experienced at least one sequelae, mainly had fatigue and mental symptoms specific to Omicron BA.2 infection compared with other common respiratory tract infections. During the second-visit, 548 (12.1%) cases of Omicron reinfection were identified. Hybrid immunity with full and booster vaccination had reduced risk of SARS-CoV-2 reinfection by 0.29-fold (95% CI: 0.63-0.81) and 0.23-fold (95% CI: 0.68-0.87), respectively. For 469 participants willing to the hospital during the first visit, those who received full (72 [IQR, 36-156]) or booster (64 [IQR, 28-132]) vaccination had significantly higher neutralizing antibody titers than those with incomplete vaccination (36 [IQR, 16-79]). Moreover, non-reinfection cases had higher neutralizing antibody titers (64 [IQR, 28-152]) compared to reinfection cases (32 [IQR, 20-69]).


Assuntos
COVID-19 , Humanos , Seguimentos , SARS-CoV-2 , China/epidemiologia , Síndrome de COVID-19 Pós-Aguda , Estudos Prospectivos , Reinfecção/epidemiologia , Anticorpos Neutralizantes , Anticorpos Antivirais
15.
RSC Adv ; 13(38): 26509-26515, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37671349

RESUMO

Recently, molybdenum disulfide (MoS2) has been extensively investigated as a promising pseudocapacitor electrode material. However, MoS2 usually exhibits inferior rate capability and cyclability, which restrain its practical application in energy storage. In this work, MoS2 nanoflowers regulated by Li2SO4 (L-MoS2) are successfully fabricated via intercalating solvated Li ions. Via appropriate intercalation of Li2SO4, MoS2 nanosheets could self-assemble to form L-MoS2 nanoflowers with an interlayer spacing of 0.65 nm. Due to the large specific surface area (23.7 m2 g-1) and high 1T phase content (77.5%), L-MoS2 as supercapacitor electrode delivers a maximum specific capacitance of 356.7 F g-1 at 1 A g-1 and maintains 49.8% of capacitance retention at 20 A g-1. Moreover, the assembled L-MoS2 symmetric supercapacitor (SSC) device displays an energy density of 6.5 W h kg-1 and 79.6% of capacitance retention after 3000 cycles.

16.
Folia Neuropathol ; 61(2): 196-208, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37587894

RESUMO

Alzheimer's disease (AD) is a chronic, neurodegenerative disorder that affects the central nervous system and is found predominantly in elderly populations. As amyloid b protein (Ab) is one of the key players responsible for the pathogenesis of AD, we sought to investigate the protective effects of fisetin in an Ab1-42-induced rat model of AD. In this model, the protective effects of fisetin on learning and memory impairment induced by Ab1-42 were determined via the Morris water maze and passive avoidance test. Furthermore, the antioxidant activity, anti-inflammation, and apoptosis effect of fisetin were investigated using biochemical and immunohistochemical methods. The results showed that intragastric (i.g.) administration of fisetin (100, 50, and 25 mg/kg) improved previous learning and memory impairments in Ab1-42-treated rats. Hippocampal tissue from these fisetin-treated rats revealed that the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) were markedly enhanced, and that the levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were significantly reduced. Meanwhile, fisetin also significantly attenuated Ab1-42-induced cholinergic dysfunction such as elevated the activity of choline acetyltransferase (ChAT) and reduced the activity of acetylcholine esterase (AChE). In addition, hippocampal tissue obtained from fisetin-treated rats revealed a reversal of Ab1-42-induced effects on apoptotic pathway protein (caspase-3) expression and inflammatory response of glial fibrillary acidic protein (GFAP). This indicated that the amount of degenerating hippocampal neurons with apoptotic features was dramatically reduced after treatment with fisetin. Collectively, these findings suggest that fisetin has potential as a treatment agent for Alzheimer's disease and that its effects occur through several mechanisms, including inhibition of oxidative stress, adjustments to previous cholinergic dysfunction, anti-inflammatory actions, and decreased apoptotic activity.


Assuntos
Doença de Alzheimer , Animais , Ratos , Doença de Alzheimer/tratamento farmacológico , Sistema Nervoso Central , Flavonóis/farmacologia , Proteínas Amiloidogênicas
17.
Clin Respir J ; 17(10): 998-1005, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37584411

RESUMO

BACKGROUND: Transbronchial lung cryobiopsy (TBLB) is routinely used to diagnose the interstitial lung disease (ILD). These results are consistent with those of surgical lung biopsy. Fluoroscopy is also used to confirm the final position of the cryoprobe; however, it can increase radiation exposure for both patients and medical care personnel. Probe-based confocal laser endomicroscopy (pCLE) is a novel optical imaging technique that allows real-time imaging at the cellular level in vivo. pCLE technology can also be used to identify malignancy, acute rejection in lung transplantation, amiodarone lung, and pulmonary alveolar proteinosis and visualize elastin fibres in the alveolar compartment. OBJECTIVES: The aim of this study is to investigate the ability of pCLE to distinguish fibrotic pulmonary issues from normal lung disease and the safety and feasibility of CLE-guided bronchoscopy and transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD). METHODS: pCLE images from 17 ILD patients were obtained during TBLB. These images were then compared with histology results to assess the correspondence rate. RESULTS: pCLE imaging of the alveolar structures was performed. Key characteristics were visible, which could potentially influence the diagnostic rate (fibrotic areas) and the complication rate (blood vessel and pleura). CONCLUSION: pCLE may reduce complications and increase the diagnostic yield. It is a potential guidance tool for cryobiopsy in the patients with ILD without fluoroscopy.


Assuntos
Doenças Pulmonares Intersticiais , Transplante de Pulmão , Humanos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/etiologia , Pulmão/diagnóstico por imagem , Pulmão/patologia , Broncoscopia/efeitos adversos , Broncoscopia/métodos , Biópsia/métodos , Lasers
18.
Adv Exp Med Biol ; 1407: 29-44, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36920690

RESUMO

Pseudotyped viruses are more and more widely used in virus research and the evaluation of antiviral products because of their high safety, simple operation, high accessibility, ease in achieving standardization, and high throughput. The development of measures based on pseudotyped virus is closely related to the characteristics of viruses, and it is also necessary to follow the principles of assay development. Only in the process of method development, where the key parameters that affect the results are systematically optimized and the preliminary established method is fully validated, can the accuracy, reliability, and repeatability of the test results be ensured. Only the method established on this basis can be transferred to different laboratories and make the results of different laboratories comparable. This paper summarizes the specific aspects and general principles in the development of assays based on pseudotyped virus, which is of reference value for the development of similar methods.


Assuntos
Antivirais , Pseudotipagem Viral , Reprodutibilidade dos Testes , Valores de Referência
19.
Adv Exp Med Biol ; 1407: 85-103, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36920693

RESUMO

Papillomavirus is difficult to culture in vitro, which limits its related research. The development of pseudotyped virus technology provides a valuable research tool for virus infectivity research, vaccine evaluation, infection inhibitor evaluation, and so on. Depending on the application fields, different measures have been developed to generate various kinds of pseudotyped papillomavirus. L1-based and L2-based HPV vaccines should be evaluated using different pseudotyped virus system. Pseudotyped papillomavirus animal models need high-titer pseudotyped virus and unique handling procedure to generate robust results. This paper reviewed the development, optimization, standardization, and application of various pseudotyped papillomavirus methods.


Assuntos
Proteínas Oncogênicas Virais , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Animais , Proteínas do Capsídeo/genética , Proteínas Oncogênicas Virais/genética , Pseudotipagem Viral , Vacinas contra Papillomavirus/genética , Vacinas contra Papillomavirus/uso terapêutico , Infecções por Papillomavirus/prevenção & controle , Anticorpos Antivirais , Papillomaviridae/genética
20.
Artigo em Inglês | MEDLINE | ID: mdl-36981886

RESUMO

Since the impoundment of the Three Gorges Reservoir area in 2003, the potential risks of geological disasters in the reservoir area have increased significantly, among which the hidden dangers of landslides are particularly prominent. To reduce casualties and damage, efficient and precise landslide susceptibility evaluation methods are important. Multiple ensemble models have been used to evaluate the susceptibility of the upper part of Badong County to landslides. In this study, EasyEnsemble technology was used to solve the imbalance between landslide and nonlandslide sample data. The extracted evaluation factors were input into three bagging, boosting, and stacking ensemble models for training, and landslide susceptibility mapping (LSM) was drawn. According to the importance analysis, the important factors affecting the occurrence of landslides are altitude, terrain surface texture (TST), distance to residences, distance to rivers and land use. The influences of different grid sizes on the susceptibility results were compared, and a larger grid was found to lead to the overfitting of the prediction results. Therefore, a 30 m grid was selected as the evaluation unit. The accuracy, area under the curve (AUC), recall rate, test set precision, and kappa coefficient of a multi-grained cascade forest (gcForest) model with the stacking method were 0.958, 0.991, 0.965, 0.946, and 0.91, respectively, which a significantly better than the values produced by the other models.


Assuntos
Desastres , Deslizamentos de Terra , Sistemas de Informação Geográfica , China , Rios
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