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1.
Bioorg Med Chem Lett ; 113: 129961, 2024 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-39278366

RESUMO

The EGFR-TK pathway is pivotal in non-small-cell lung cancer (NSCLC) treatment, drugs targeting both EGFR wild-type and mutant tumor cells are still urgently needed. The focus of our study is on ATP-competitive inhibitors crucial for NSCLC therapy, specifically targeting the epidermal growth factor receptor (EGFR). A series of derivatives of Erlotinib and Icotinib were developed by incorporating a macrocyclic polyamine into a quinazoline scaffold to enhance their inhibitory activity against drug-resistant cells. The compounds exhibit modest activity against EGFR triple mutants (EGFRdel19/T790M/C797S). Compound b demonstrated slightly improved inhibition activity against PC-9del19/T790M/C797S (IC50 = 496.3 nM). This could provide some insights for optimizing EGFR inhibitors, particularly in the context of EGFR triple mutants.

2.
J Adv Nurs ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164061

RESUMO

AIMS: To systematically evaluate and analyse literature concerning the factors influencing the implementation of clinical practice guidelines related to enteral nutrition in the adult intensive care unit. BACKGROUND: Guidelines serve as crucial tools for guiding clinical practice. However, a significant gap persists between current clinical practice and guidelines pertaining to enteral nutrition. It is essential to identify the reasons behind this disparity to foster clinical transformation. METHODS: A mixed-methods systematic review. DATA SOURCES: A systematic search was conducted across PubMed, Embase, Medline, Cochrane, PsycINFO and CNKI databases to identify impediments and facilitators to the implementation of ICU clinical practice guidelines related to enteral nutrition. The types of studies included quantitative, qualitative and mixed-methods studies. The search spanned from January 2003 to January 2024 and was updated in May 2024. The quality assessment of the included literature was conducted using the Mixed-Methods Study Evaluation Tool (MMAT). Data analysis was performed using a data-based convergent integration approach. The protocol for this study was prospectively registered (PROSPERO2023, CRD42023483287). RESULTS: Twenty papers were finally included, and 65 findings were extracted, integrating a total of three categories, Category 1: healthcare provider factors, including three sub-themes: knowledge of guideline-related knowledge and awareness of guideline application; social/professional roles and identity domains; beliefs, attitudes and self-efficacy; collaboration, Category 2: practice environments, including two sub-themes: environmental factors and resource areas; systems and behavioural norms, Category 3: patient values and nutritional support preferences including two sub-themes: patient disease status and value orientation. CONCLUSION: Healthcare professionals should analyse obstacles and facilitators to guideline implementation from multiple perspectives, strengthen healthcare collaboration, improve education and training systems, correct misperceptions and increase awareness of evidence-based practice.

3.
Harmful Algae ; 137: 102678, 2024 08.
Artigo em Inglês | MEDLINE | ID: mdl-39003029

RESUMO

Raphidiopsis blooms are notorious for cyanotoxin formation and strong invasiveness, threatening the stability of aquatic ecosystems and human health. The protozoa Paramecium can potentially serve as an organism for controlling Raphidiopsis blooms owing to its grazing effect. However, the grazing ability of Paramecium is largely determined by the size of the prey, and the population of Raphidiopsis consists of filaments of varying lengths and sizes. The selective grazing behavior of Paramecium toward short-length or small-sized filaments in the Raphidiopsis population, as opposed to long filaments, remains unclear. Therefore, in this study, we co-cultured the predator Paramecium sp. with different initial abundances and the prey Raphidiopsis raciborskii to explore this knowledge gap. Our results suggested that: (1) the population of R. raciborskii declined under the selective grazing effect of Paramecium sp. on short filaments, whereas R. raciborskii with long filaments survived; (2) the growth of Paramecium sp. feeding on the same abundance of R. raciborskii was reduced at higher initial abundances, whereas its carrying capacity exhibited an opposite trend; (3) under ingestion by Paramecium sp., the morphology of R. raciborskii developed in the direction of becoming larger, and higher initial abundances of Paramecium sp. intensified this process; (4) increasing initial abundance of Paramecium sp. aggravated the decline of R. raciborskii photosynthetic activity. Therefore, the grazing effect of Paramecium sp. on R. raciborskii mainly affects filaments of short length or small size. Collectively, these results clarify the inter-species interaction between the protozoa Paramecium and filamentous cyanobacteria Raphidiopsis, including population dynamics and morphological and physiological changes in the predator and prey. Such insights into the interactions between Paramecium and R. raciborskii may have implications for the biological control of blooms caused by filamentous cyanobacteria.


Assuntos
Paramecium , Paramecium/fisiologia , Cianobactérias/fisiologia , Cadeia Alimentar , Comportamento Predatório/fisiologia
4.
J Hazard Mater ; 477: 135152, 2024 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-39047554

RESUMO

Raphidiopsis raciborskii (R. raciborskii) forms harmful cyanobacterial blooms globally, and poses a great threat to the safety of drinking water and public health. There is a great need to develop eco-friendly biological alternative measures to mitigate mass blooms of R. raciborskii. However, previous rare studies on algicidal microorganisms against R. raciborskii restricted this aim. Recently, an algicidal bacterium Streptomyces sp. HY (designated HY) was identified with flavones producing ability, and could remove up to 98.73 % of R. raciborskii biomass within 48 h by directly attacking the cyanobacterium and release of algicidal substances (i.e., flavonoids) with a inoculum ratio of 5 %. Algicidal rate of HY was enhanced by 88.05 %, 89.33 % under dark and light, and full-light conditions respectively, when compared with the dark condition. Its algicidal substances were stable in a broad range of temperature (-80-55 °C) and pH (3-11) conditions, and all treated groups exhibited ≈ 100 % algicidal rate at day 3. HY treatment disrupted the photosynthesis system and triggered serious oxidative stress resulting in severe morphological injury. Thereby, HY treatment significantly affected expression levels of several essential genes (i.e., psbA, psaB, rbcL, ftsZ, recA, grpE), and simultaneously inhibited the biosynthesis and release of cylindrospermopsin. Yet, HY treatment didn't show any toxicity to zebrafish test embryos. Such results indicate that HY is a promising algicidal candidate strain to control global R. raciborskii blooms, and holds great promises for an effective biological measure to sustain water safety.


Assuntos
Proliferação Nociva de Algas , Streptomyces , Peixe-Zebra , Streptomyces/metabolismo , Proliferação Nociva de Algas/efeitos dos fármacos , Animais , Floculação , Flavonoides/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Flavonas/toxicidade , Flavonas/farmacologia , Flavonas/química , Cianobactérias
6.
Am J Transl Res ; 16(6): 2501-2508, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006257

RESUMO

OBJECTIVES: To assess the efficacy, safety, and impact on serum cytokines of olopatadine hydrochloride (OLP) combined with desloratadine citrate disodium (DES) in treating urticaria. METHODS: We retrospectively analyzed 114 urticaria patients treated at the Affiliated Hospital of Xinyang Vocational and Technical College from March 2020 to March 2023. The control group (55 patients) received DES, while the research group (59 patients) received OLP+DES combination therapy. We compared efficacy, safety (including epigastric pain, dry mouth, lethargy, dizziness, and fatigue), changes in serum cytokines (interleukin [IL]-2, IL-4, and interferon [IFN]-γ), symptom resolution (wheal number, wheal size, and itching degree), and 3-month recurrence rates. A univariate analysis was also conducted to identify factors influencing urticaria recurrence. RESULTS: The research group exhibited a significantly higher overall efficacy rate, lower incidence of adverse events, and reduced recurrence rates at 3 months (all P<0.05) compared to the control group. Post-treatment, the research group showed significant increases in IL-2 and IFN-γ levels and reductions in IL-4 levels, wheal number, wheal size, and itching degree (all P<0.05). Factors such as history of drinking/smoking, IL-2 levels, and treatment method were associated with urticaria recurrence (all P<0.05). CONCLUSIONS: The combination of OLP and DES is an effective and safe treatment option for urticaria, significantly improving serum cytokine profiles, alleviating symptoms, and reducing recurrence risk.

7.
Acad Radiol ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39003227

RESUMO

RATIONALE AND OBJECTIVES: Prior to clinical presentations of Alzheimer's Disease (AD), neuropathological changes, such as amyloid-ß and brain atrophy, have accumulated at the earlier stages of the disease. The combination of such biomarkers assessed by multiple modalities commonly improves the likelihood of AD etiology. We aimed to explore the discriminative ability of Aß PET features and whether combining Aß PET and structural MRI features can improve the classification performance of the machine learning model in older healthy control (OHC) and mild cognitive impairment (MCI) from AD. MATERIAL AND METHODS: We collected 94 AD patients, 82 MCI patients, and 85 OHC from three different cohorts. 17 global/regional Aß features in Centiloid, 122 regional volume, and 68 regional cortical thickness were extracted as imaging features. Single or combined modality features were used to train the random forest model on the testing set. The top 10 features were sorted based on the Gini index in each binary classification. RESULTS: The results showed that AUC scores were 0.81/0.86 and 0.69/0.68 using sMRI/Aß PET features on the testing set in differentiating OHC and MCI from AD. The performance was improved while combining two-modality features with an AUC of 0.89 and an AUC of 0.71 in two classifications. Compared to sMRI features, particular Aß PET features contributed more to differentiating AD from others. CONCLUSION: Our study demonstrated the discriminative ability of Aß PET features in differentiating AD from OHC and MCI. A combination of Aß PET and structural MRI features can improve the RF model performance.

9.
JAMA ; 332(5): 380-389, 2024 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-38762797

RESUMO

Importance: Current treatments for idiopathic pulmonary fibrosis slow the rate of lung function decline, but may be associated with adverse events that affect medication adherence. In phase 2 trials, pamrevlumab (a fully human monoclonal antibody that binds to and inhibits connective tissue growth factor activity) attenuated the progression of idiopathic pulmonary fibrosis without substantial adverse events. Objective: To assess the efficacy and safety of pamrevlumab for patients with idiopathic pulmonary fibrosis. Design, Setting, and Participants: Phase 3 randomized clinical trial including 356 patients aged 40 to 85 years with idiopathic pulmonary fibrosis who were not receiving antifibrotic treatment with nintedanib or pirfenidone at enrollment. Patients were recruited from 117 sites in 9 countries between July 18, 2019, and July 29, 2022; the last follow-up encounter occurred on August 28, 2023. Interventions: Pamrevlumab (30 mg/kg administered intravenously every 3 weeks; n = 181) or placebo (n = 175) for 48 weeks. Main Outcomes and Measures: The primary outcome was absolute change in forced vital capacity (FVC) from baseline to week 48. There were 5 secondary outcomes (including time to disease progression, which was defined as a decline of ≥10% in predicted FVC or death). The exploratory outcomes included patient-reported symptoms. Adverse events were reported. Results: Among 356 patients (mean age, 70.5 years; 258 [72.5%] were men; 221 [62.1%] were White), 277 (77.8%) completed the trial. There was no significant between-group difference for absolute change in FVC from baseline to week 48 (least-squares mean, -260 mL [95% CI, -350 to -170 mL] in the pamrevlumab group vs -330 mL [95% CI, -430 to -230 mL] in the placebo group; mean between-group difference, 70 mL [95% CI, -60 to 190 mL], P = .29). There were no significant between-group differences in any of the secondary outcomes or in the patient-reported outcomes. In the pamrevlumab group, there were 160 patients (88.4%) with treatment-related adverse events and 51 patients (28.2%) with serious adverse events vs 151 (86.3%) and 60 (34.3%), respectively, in the placebo group. During the study, 23 patients died in each group (12.7% in the pamrevlumab group vs 13.1% in the placebo group). Conclusions and Relevance: Among patients with idiopathic pulmonary fibrosis treated with pamrevlumab or placebo, there was no statistically significant between-group difference for the primary outcome of absolute change in FVC from baseline to week 48. Trial Registration: ClinicalTrials.gov Identifier: NCT03955146.


Assuntos
Anticorpos Monoclonais Humanizados , Fibrose Pulmonar Idiopática , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Fator de Crescimento do Tecido Conjuntivo/antagonistas & inibidores , Progressão da Doença , Método Duplo-Cego , Fibrose Pulmonar Idiopática/diagnóstico , Fibrose Pulmonar Idiopática/tratamento farmacológico , Capacidade Vital/efeitos dos fármacos , Infusões Intravenosas , Medidas de Resultados Relatados pelo Paciente
10.
Neuroradiology ; 66(9): 1537-1551, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38676749

RESUMO

PURPOSE: The Centiloid project helps calibrate the quantitative amyloid-ß (Aß) load into a unified Centiloid (CL) scale that allows data comparison across multi-site. How the smaller regional amyloid converted into CL has not been attempted. We first aimed to express regional Aß deposition in CL using [18F]Flutemetamol and evaluate regional Aß deposition in CL with that in standardized uptake value ratio (SUVr). Second, we aimed to determine the presence or absence of focal Aß deposition by measuring regional CL in equivocal cases showing negative global CL. METHODS: Following the Centiloid project pipeline, Level-1 replication, Level-2 calibration, and quality control were completed to generate corresponding Centiloid conversion equations to convert SUVr into Centiloid at regional levels. In equivocal cases, the regional CL was compared with visual inspection to evaluate regional Aß positivity. RESULTS: 14 out of 16 regional conversions from [18F]Flutemetamol SUVr to Centiloid successfully passed the quality control, showing good reliability and relative variance, especially precuneus/posterior cingulate and prefrontal regions with good stability for Centiloid scaling. The absence of focal Aß deposition could be detected by measuring regional CL, showing a high agreement rate with visual inspection. The regional Aß positivity in the bilateral anterior cingulate cortex was most prevalent in equivocal cases. CONCLUSION: The expression of regional brain Aß deposition in CL with [18F]Flutemetamol has been attempted in this study. Equivocal cases had focal Aß deposition that can be detected by measuring regional CL.


Assuntos
Peptídeos beta-Amiloides , Compostos de Anilina , Benzotiazóis , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Humanos , Peptídeos beta-Amiloides/metabolismo , Feminino , Masculino , Idoso , Tomografia por Emissão de Pósitrons/métodos , Reprodutibilidade dos Testes , Doença de Alzheimer/metabolismo , Doença de Alzheimer/diagnóstico por imagem , Pessoa de Meia-Idade , Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Calibragem
11.
Emotion ; 24(6): 1417-1427, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38512195

RESUMO

Previous research has shown mixed results regarding the relationship between social class and children's prosocial behavior. The current study aims to further our understanding of these findings by exploring the relationship between social class and children's prosocial behavior in a moral context. Study 1 (N = 833) found that when a target child pursued a morally negative goal and subsequently experienced misfortune, children from higher social class, compared to those from lower social class, experienced greater schadenfreude and exhibited less prosocial behavior. The relation between social class and prosocial behavior was mediated by schadenfreude. Study 2 (N = 389) investigated whether the greater schadenfreude experienced by children from higher social class was due to a weaker empathic response to misfortune or a stronger sense of deservingness. The results revealed a sequential mediation effect of social class on prosocial behavior through deservingness and schadenfreude. These findings provide insight into the impact of social class on the development of children's moral judgment, emotions, and behavior. (PsycInfo Database Record (c) 2024 APA, all rights reserved).


Assuntos
Comportamento Infantil , Empatia , Princípios Morais , Comportamento Social , Classe Social , Humanos , Masculino , Feminino , Criança , Empatia/fisiologia , Emoções
12.
Environ Pollut ; 348: 123878, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38548158

RESUMO

Addressing notorious and worldwide Microcystis blooms, mechanical algae harvesting is an effective emergency technology for bloom mitigation and removal of nutrient loads in waterbodies. However, the absence of effective methods for removal of cyanobacterial toxins, e.g., microcystins (MCs), poses a challenge to recycle the harvested Microcystis biomass. In this study, we therefore introduced a novel approach, the "captured biomass-MlrA enzymatic MC degradation", by enriching microcystinase A (MlrA) via fermentation and spraying it onto salvaged Microcystis slurry to degrade all MCs. After storing the harvested Microcystis slurry, a rapid release of extracellular MCs occurred within the initial 8 h, reaching a peak concentration of 5.33 µg/mL at 48 h during the composting process. Upon spraying the recombinant MlrA crude extract (about 3.36 U) onto the Microcystis slurry in a ratio of 0.1% (v/v), over 95% of total MCs were degraded within a 24-h period. Importantly, we evaluated the reliability and safety of using MlrA extracts to degrade MCs. Results showed that organic matter/nutrient contents, e.g. soluble proteins, polysaccharides, phycocyanin and carotenoids, were not significantly altered. Furthermore, the addition of MlrA extracts did not significantly change the bacterial community composition and diversity in the Microcystis slurry, indicating that the MlrA extracts did not increase the risk of pathogenic bacteria. Our study provides an effective and promising method for the pre-treatment of harvested Microcystis biomass, highlighting an ecologically sustainable framework for addressing Microcystis blooms.


Assuntos
Cianobactérias , Microcystis , Microcistinas/metabolismo , Reprodutibilidade dos Testes , Cianobactérias/metabolismo , Microcystis/metabolismo , Biomassa
13.
Sci Total Environ ; 927: 171955, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38547994

RESUMO

With rapid industrialization and urbanization, the risk of summer heat exposure for urban dwellers has increased. The use of air conditioners (ACs) has become the most common personal cooling strategy, but further increasing fossil fuel consumption. As sustainable and affordable cooling strategies, urban parks can reduce heat exposure and substitute a part of air conditioners use. This study evaluates the heat exposure reduction from personal cooling to urban parks based on satellite images, questionnaire surveys, and network analysis in Liuzhou, one tropical city in China. We found that residents with lower income had a higher risk of heat exposure. Among the respondents, 85 % of residents chose to use ACs to alleviate high temperatures in summer, and 81.8 % among them were willing to access park cooling area (PCA) to cool off instead of using ACs. About one third parks could serve as potential alternatives (with temperatures <28 °C) to air conditioning, reducing carbon emissions by 175.93 tons per day during the hot summer and offsetting 2.5 % of urban fossil fuel carbon emissions. The design of parks should give more consideration to elder people and provide a good cooling platform for various social income groups. Future planning should also focus on accessibility to enable residents to fully utilize the parks. Building parks within 34.10 ha would provide a more efficient use of land. This research guides sustainable, high-quality growth in industrial cities and might contribute to promotion of low-carbon cities and social equity.


Assuntos
Cidades , Temperatura Alta , China , Humanos , Ar Condicionado , Parques Recreativos , Urbanização , Exposição Ambiental/estatística & dados numéricos
14.
Water Res ; 254: 121344, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38430754

RESUMO

Changes in salinity have a profound influence on ecological services and functions of inland freshwater ecosystems, as well as on the shaping of microbial communities. Bacterioplankton, generally classified into free-living (FL) and particle-attached (PA) forms, are main components of freshwater ecosystems and play key functional roles for biogeochemical cycling and ecological stability. However, there is limited knowledge about the responses of community stability of both FL and PA bacteria to salinity fluctuations. Here, we systematically explored changes in community stability of both forms of bacteria based on high-frequency sampling in a shallow urban reservoir (Xinglinwan Reservoir) in subtropical China for 3 years. Our results indicated that (1) salinity was the strongest environmental factor determining FL and PA bacterial community compositions - rising salinity increased the compositional stability of both bacterial communities but decreased their α-diversity. (2) The community stability of PA bacteria was significantly higher than that of FL at high salinity level with low salinity variance scenarios, while the opposite was found for FL bacteria, i.e., their stability was higher than PA bacteria at low salinity level with high variance scenarios. (3) Both bacterial traits (e.g., bacterial genome size and interaction strength of rare taxa) and precipitation-induced factors (e.g., changes in salinity and particle) likely contributed collectively to differences in community stability of FL and PA bacteria under different salinity scenarios. Our study provides additional scientific basis for ecological management, protection and restoration of urban reservoirs under changing climatic and environmental conditions.


Assuntos
Ecossistema , Microbiota , Salinidade , Lagos/microbiologia , Bactérias/genética , Microbiota/fisiologia , Organismos Aquáticos , RNA Ribossômico 16S/genética
15.
Nat Commun ; 15(1): 1995, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443404

RESUMO

Cardiac macrophage contributes to the development of cardiac fibrosis, but factors that regulate cardiac macrophages transition and activation during this process remains elusive. Here we show, by single-cell transcriptomics, lineage tracing and parabiosis, that cardiac macrophages from circulating monocytes preferentially commit to macrophage-to-myofibroblast transition (MMT) under angiotensin II (Ang II)-induced hypertension, with accompanying increased expression of the RNA N6-methyladenosine demethylases, ALKBH5. Meanwhile, macrophage-specific knockout of ALKBH5 inhibits Ang II-induced MMT, and subsequently ameliorates cardiac fibrosis and dysfunction. Mechanistically, RNA immunoprecipitation sequencing identifies interlukin-11 (IL-11) mRNA as a target for ALKBH5-mediated m6A demethylation, leading to increased IL-11 mRNA stability and protein levels. By contrast, overexpression of IL11 in circulating macrophages reverses the phenotype in ALKBH5-deficient mice and macrophage. Lastly, targeted delivery of ALKBH5 or IL-11 receptor α (IL11RA1) siRNA to monocytes/macrophages attenuates MMT and cardiac fibrosis under hypertensive stress. Our results thus suggest that the ALKBH5/IL-11/IL11RA1/MMT axis alters cardiac macrophage and contributes to hypertensive cardiac fibrosis and dysfunction in mice, and thereby identify potential targets for cardiac fibrosis therapy in patients.


Assuntos
Adenina , Hipertensão , Interleucina-11 , Animais , Humanos , Camundongos , Adenina/análogos & derivados , Homólogo AlkB 5 da RNA Desmetilase , Angiotensina II , Cardiotônicos , Macrófagos , Miofibroblastos , RNA
17.
J Wound Care ; 33(Sup2a): xx-xxvii, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38324420

RESUMO

OBJECTIVE: Negative pressure wound therapy (NPWT) is considered to be an effective technique to promote the healing of various wounds. The aim of this study was to evaluate different wound dressings combined with NPWT in treating wounds in Wuzhishan pigs. METHOD: Excisions were made in the backs of the pigs and were covered with polyvinyl alcohol (PVA) dressing, polyurethane (PU) dressing or PU dressing with non-adherent membrane (PU-non-ad). NPWT was applied to the wound site. In the control group, basic occlusive dressing (gauze) without NPWT was applied. On days 0, 3, 7, 14, 21 and 28 post-surgery, the wound size was measured during dressing change, and wound healing rate (WHR) was calculated. In addition, blood perfusion within 2cm of the surrounding wound was measured by laser doppler flowmetry. Dressing specimen was collected and microbiology was analysed. Granulation tissues from the central part of the wounds were analysed for histology, vascular endothelial growth factor (VEGF) and cluster of differentiation 31 (CD31) mRNA expression. RESULTS: The PU-non-ad-NPWT significantly (p<0.01) accelerated wound healing in the pigs. Further pathological analysis revealed that the non-adherent membrane effectively protected granulation tissue formation in PU-NPWT treated wounds. The blood perfusion analysis suggested that the non-adherent membrane improved the blood supply to the wound area. Microbiological analysis showed that non-adherent membrane decreased the bacterial load in the PU-NPWT dressing. VEGF and CD31 mRNA expression was upregulated in the wound tissue from the PU-non-ad-NPWT treated groups. CONCLUSION: In this study, the PU dressing with non-adherent membrane was an ideal dressing in NPWT-assisted wound healing.


Assuntos
Tratamento de Ferimentos com Pressão Negativa , Animais , Suínos , Tratamento de Ferimentos com Pressão Negativa/métodos , Poliuretanos , Fator A de Crescimento do Endotélio Vascular , Bandagens , RNA Mensageiro
18.
Heliyon ; 10(4): e24985, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38370262

RESUMO

Background: During the regression of hypertrophic scars, autophagy and apoptosis are the main ways of cell death. Recent investigations demonstrated effective inhibition of resveratrol on hypertrophic scar fibroblasts (HSFs). But its therapeutic value is limited by chemical instability and hydrophobicity, as well as the mechanism of its role in regulation of autophagy and apoptosis remains unknown. Aim of the study: We prepared a mesoporous silica nanoparticle laden with resveratrol (MSN@Res) which can effectively improve the solubility and stability of resveratrol. The purpose of this study was to investigate whether MSN@Res regulate autophagy and apoptosis of HSFs via inhibition of ROS/p38/HIF-1α/p53 signaling axis, as to reveal its pharmacological action and target. Materials and methods: Network pharmacology, molecular docking, and in vitro assays were carried out in this study. An in vitro model of fibroblasts cultivated in hypoxic and ischemic situations was established to simulate the scar in the proliferative phase. Results: MSN@Res surpresses HSFs by reducing physiological autophagy and inducing apoptosis, autosis may be another cell death involed in this process. According to the network pharmacological analysis and molecular docking, the mechanism by which MSN@Res alleviates hypertrophic scar may be closely related to the MAPK signaling pathway. MSN@Res significantly downregulate the expression of HIF-1α and p53 through the inhibition of ROS induced p38-MAPK phosphorylation with corresponding changes in the expression of autophagy and apoptosis related protein. Conclusion: MSN@Res is a novel drug delivery system with excellent chemical stability and drug release performance. It can inhibit protective autophagy of fibroblasts in hypoxic environment, and induce the apoptosis and autosis via the ROS -mediated p38-MAPK/HIF-1α/p53 signaling axis.

19.
Sci Rep ; 14(1): 4180, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378747

RESUMO

A precise, scalable, and computationally efficient mathematical framework is proposed for region-wide autonomous electric vehicle (AEV) fleet management, sizing and infrastructure planning for urban ride-hailing services. A comprehensive techno-economic analysis in New York City is conducted not only to calculate the societal costs but also to quantify the environmental and health benefits resulting from reduced emissions. The results reveal that strategic fleet management can reduce fleet size and unnecessary cruising mileage by up to 40% and 70%, respectively. This alleviates traffic congestion, saves travel time, and further reduces fleet sizes. Besides, neither large-battery-size AEVs nor high-power charging infrastructure is necessary to achieve efficient service. This effectively alleviates financial and operational burdens on fleet operators and power systems. Moreover, the reduced travel time and emissions resulting from efficient fleet autonomy create an economic value that exceeds the total capital investment and operational costs of fleet services.

20.
J Lipid Res ; 65(2): 100499, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38218337

RESUMO

Ferroptosis is a novel cell death mechanism that is mediated by iron-dependent lipid peroxidation. It may be involved in atherosclerosis development. Products of phospholipid oxidation play a key role in atherosclerosis. 1-palmitoyl-2-glutaroyl-sn-glycero-3-phosphocholine (PGPC) is a phospholipid oxidation product present in atherosclerotic lesions. It remains unclear whether PGPC causes atherosclerosis by inducing endothelial cell ferroptosis. In this study, human umbilical vein endothelial cells (HUVECs) were treated with PGPC. Intracellular levels of ferrous iron, lipid peroxidation, superoxide anions (O2•-), and glutathione were detected, and expression of fatty acid binding protein-3 (FABP3), glutathione peroxidase 4 (GPX4), and CD36 were measured. Additionally, the mitochondrial membrane potential (MMP) was determined. Aortas from C57BL6 mice were isolated for vasodilation testing. Results showed that PGPC increased ferrous iron levels, the production of lipid peroxidation and O2•-, and FABP3 expression. However, PGPC inhibited the expression of GPX4 and glutathione production and destroyed normal MMP. These effects were also blocked by ferrostatin-1, an inhibitor of ferroptosis. FABP3 silencing significantly reversed the effect of PGPC. Furthermore, PGPC stimulated CD36 expression. Conversely, CD36 silencing reversed the effects of PGPC, including PGPC-induced FABP3 expression. Importantly, E06, a direct inhibitor of the oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine IgM natural antibody, inhibited the effects of PGPC. Finally, PGPC impaired endothelium-dependent vasodilation, ferrostatin-1 or FABP3 inhibitors inhibited this impairment. Our data demonstrate that PGPC impairs endothelial function by inducing endothelial cell ferroptosis through the CD36 receptor to increase FABP3 expression. Our findings provide new insights into the mechanisms of atherosclerosis and a therapeutic target for atherosclerosis.


Assuntos
Aterosclerose , Cicloexilaminas , Ferroptose , Fenilenodiaminas , Animais , Camundongos , Humanos , Fosfolipídeos , Fosforilcolina , Éteres Fosfolipídicos/metabolismo , Éteres Fosfolipídicos/farmacologia , Camundongos Endogâmicos C57BL , Células Endoteliais da Veia Umbilical Humana/metabolismo , Endotélio/metabolismo , Glutationa/metabolismo , Ferro/metabolismo , Proteína 3 Ligante de Ácido Graxo
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