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1.
J Colloid Interface Sci ; 677(Pt A): 378-389, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39096706

RESUMO

HYPOTHESIS: Nanoparticle-stabilized foams are extremely stable, and flame retardant inorganic nanoparticles should be able to add sealing capacity of firefighting foams on flammable liquid fuels, and hence enhance fire extinguishment performance on liquid fuel fire. In practice, how do flame retardant nanoparticles resist the destructive effect of oil molecules on foam and tune foam properties? EXPERIMENTS: We have prepared a nanoparticle-enhanced foam comprising of hydrocarbon surfactant, short-chain fluorocarbon surfactant, and nanoparticles. The interactions among nanoparticles and surfactant molecules were characterized by using dynamic surface tension and conductivity. Stability, rheology, and oil resistivity on liquid fuel of the nanoparticle-enhanced foam were evaluated systematically. Fire suppression effectiveness of the foams was verified based on a standard experiment. FINDINGS: Foam stability and oil resistivity were enhanced due to self-assembled network structures formed by jammed aggregates composed by nanoparticles and surfactants in Plateau borders and bubble films, providing structural recoverability and enhanced viscoelasticity within foam. Foams containing nano-SiO2, nano-CaCO3, nano-Al(OH)3, and nano-Mg(OH)2 show difference in fire extinguishment due to different ability to enhance foam properties. Foam containing nano-Al(OH)3 shows the strongest adaptation and could shorten fire extinguishing time by 2 times and prolong burn-back time by 2.3 times compared with commercial product.

2.
Physiol Plant ; 176(4): e14432, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38981735

RESUMO

WRKYs play important roles in plant stress resistance. However, the role of WRKYs in non-heading Chinese cabbage (Brassica campestris ssp. chinensis) against Botrytis cinerea (B. cinerea) remains poorly understood. Herein, the expression of BcWRKY1 was induced by B. cinerea. Further, the role of BcWRKY1 in B. cinerea infection was identified. Silencing of BcWRKY1 in non-heading Chinese cabbage enhanced plant resistance to B. cinerea. After B. cinerea inoculation, BcWRKY1-silencing plants exhibited lower reactive oxygen species (ROS) content, higher jasmonic acid (JA) content, and the expression level of JA biosynthesis genes, BcOPR3, BcLOX3-1 and BcLOX3-2 were upregulated. Overexpression of BcWRKY1 in Arabidopsis exhibited a complementary phenotype. By directly targeting W-boxes in the promoter of BcLOX3-2, BcWRKY1 inhibited the transcription of this gene. In addition, 13 candidate interacting proteins of BcWRKY1 were identified by yeast two-hybrid (Y2H) screening, and the interaction between BcWRKY1 and BcCaM6 weakened the inhibition of BcLOX3-2. In summary, our findings suggest that BcWRKY1 interacts with BcCaM6 to negatively regulate disease resistance.


Assuntos
Botrytis , Brassica , Ciclopentanos , Resistência à Doença , Regulação da Expressão Gênica de Plantas , Oxilipinas , Doenças das Plantas , Proteínas de Plantas , Botrytis/fisiologia , Botrytis/patogenicidade , Ciclopentanos/metabolismo , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Oxilipinas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Resistência à Doença/genética , Brassica/microbiologia , Brassica/genética , Brassica/metabolismo , Arabidopsis/microbiologia , Arabidopsis/genética , Arabidopsis/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Plantas Geneticamente Modificadas
3.
Sci Rep ; 14(1): 15324, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961143

RESUMO

Diabetic cardiomyopathy (DCM) is a common cardiovascular complication of diabetes, which may threaten the quality of life and shorten life expectancy in the diabetic population. However, the molecular mechanisms underlying the diabetes cardiomyopathy are not fully elucidated. We analyzed two datasets from Gene Expression Omnibus (GEO). Differentially expressed and weighted gene correlation network analysis (WGCNA) was used to screen key genes and molecules. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) network analysis were constructed to identify hub genes. The diagnostic value of the hub gene was evaluated using the receiver operating characteristic (ROC). Quantitative real-time PCR (RT-qPCR) was used to validate the hub genes. A total of 13 differentially co-expressed modules were selected by WGCNA and differential expression analysis. KEGG and GO analysis showed these DEGs were mainly enriched in lipid metabolism and myocardial hypertrophy pathway, cytomembrane, and mitochondrion. As a result, six genes were identified as hub genes. Finally, five genes (Pdk4, Lipe, Serpine1, Igf1r, and Bcl2l1) were found significantly changed in both the validation dataset and experimental mice with DCM. In conclusion, the present study identified five genes that may help provide novel targets for diagnosing and treating DCM.


Assuntos
Biologia Computacional , Cardiomiopatias Diabéticas , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Cardiomiopatias Diabéticas/genética , Biologia Computacional/métodos , Animais , Camundongos , Mapas de Interação de Proteínas/genética , Humanos , Inibidor 1 de Ativador de Plasminogênio/genética , Perfilação da Expressão Gênica , Receptor IGF Tipo 1/genética , Ontologia Genética , Regulação da Expressão Gênica
4.
Sci Rep ; 14(1): 15627, 2024 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972909

RESUMO

Apparently, understanding airway management status may help to reduce risk and improve clinical practice. Given these facts, our team conducted a second survey on the current status of airway management for mainland China following our 2016 national airway survey. The national survey was conducted from November 7 to November 28, 2022. An electronic survey was sent to the New Youth Anesthesia Forum, where Chinese anesthesiologists completed the questionnaire via WeChat. A total of 3783 respondents completed the survey, with a response rate of 72.14%. So far, in 2022, 34.84% of anesthesiologists canceled or delayed surgery at least once due to difficult airway. For the anticipated difficult airway management, 66.11% of physicians would choose awake intubation under sedation and topical anesthesia, while the percentage seeking help has decreased compared to the 2016 survey. When encountering an emergency, 74.20% of respondents prefer to use the needle cricothyrotomy, albeit less than a quarter have actually performed it. Anesthesiologists with difficult airway training experience reached 72.96%, with a significant difference in participation between participants in Tier 3 hospitals and those in other levels of hospitals (P < 0.001). The videolaryngoscope, laryngeal mask, and flexible intubation scope were equipped at 97.18%, 95.96%, and 62.89%, respectively. Additionally, the percentage of brain damage or death caused by difficult airways was significantly decreased. The study may be the best reference for understanding the current status of airway management in China, revealing the current advancements and deficiencies. The future focus of airway management remains on training and education.


Assuntos
Manuseio das Vias Aéreas , Humanos , China , Manuseio das Vias Aéreas/métodos , Manuseio das Vias Aéreas/estatística & dados numéricos , Inquéritos e Questionários , Intubação Intratraqueal/estatística & dados numéricos , Intubação Intratraqueal/métodos , Masculino , Anestesiologistas , Feminino , Adulto , Máscaras Laríngeas
5.
Front Endocrinol (Lausanne) ; 15: 1385167, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948526

RESUMO

Background: Thyroid nodules, increasingly prevalent globally, pose a risk of malignant transformation. Early screening is crucial for management, yet current models focus mainly on ultrasound features. This study explores machine learning for screening using demographic and biochemical indicators. Methods: Analyzing data from 6,102 individuals and 61 variables, we identified 17 key variables to construct models using six machine learning classifiers: Logistic Regression, SVM, Multilayer Perceptron, Random Forest, XGBoost, and LightGBM. Performance was evaluated by accuracy, precision, recall, F1 score, specificity, kappa statistic, and AUC, with internal and external validations assessing generalizability. Shapley values determined feature importance, and Decision Curve Analysis evaluated clinical benefits. Results: Random Forest showed the highest internal validation accuracy (78.3%) and AUC (89.1%). LightGBM demonstrated robust external validation performance. Key factors included age, gender, and urinary iodine levels, with significant clinical benefits at various thresholds. Clinical benefits were observed across various risk thresholds, particularly in ensemble models. Conclusion: Machine learning, particularly ensemble methods, accurately predicts thyroid nodule presence using demographic and biochemical data. This cost-effective strategy offers valuable insights for thyroid health management, aiding in early detection and potentially improving clinical outcomes. These findings enhance our understanding of the key predictors of thyroid nodules and underscore the potential of machine learning in public health applications for early disease screening and prevention.


Assuntos
Aprendizado de Máquina , Nódulo da Glândula Tireoide , Nódulo da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/epidemiologia , Nódulo da Glândula Tireoide/diagnóstico por imagem , Humanos , Feminino , Masculino , China/epidemiologia , Estudos Transversais , Pessoa de Meia-Idade , Adulto , Detecção Precoce de Câncer/métodos , Idoso , Programas de Rastreamento/métodos , Ultrassonografia/métodos
6.
Int J Chron Obstruct Pulmon Dis ; 19: 1457-1469, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38948909

RESUMO

Purpose: This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide. Methods: We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events. Results: We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc. Conclusion: Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.


Assuntos
Administração Intranasal , Sistemas de Notificação de Reações Adversas a Medicamentos , Bases de Dados Factuais , Farmacovigilância , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Administração por Inalação , Estados Unidos/epidemiologia , Fatores de Risco , Idoso , Medição de Risco , Adulto , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , United States Food and Drug Administration , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/diagnóstico
7.
Minerva Anestesiol ; 90(7-8): 607-617, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39021136

RESUMO

BACKGROUND: Novel airway devices are becoming widely available, yet it is unclear whether the techniques or preferences of airway practitioners for airway management have been impacted. Given these facts, a cross-sectional study of the current status of airway management in mainland China was conducted and compared with previous survey findings. METHODS: The national survey was conducted from November 7th to November 28th, 2022. An electronic survey was sent to the New Youth Anesthesia Forum to examine the availability of airway devices, preference for front-of-neck access (FONA) techniques, the incidence of adverse airway events, and the status of airway management training. RESULTS: Questionnaires were completed by 3783 respondents, with a response rate of 72.14%. So far, the availability of optical airway devices has improved dramatically, with the availability of videolaryngoscopes reaching 97.18%. When encountering "cannot intubate, cannot ventilate" (CICV) scenarios, the majority of respondents would prefer needle cricothyrotomy to establish FONA. However, less than a quarter of respondents had actually performed it. Moreover, the incidence of airway adverse events from 2016 to 2022 was 11.48%, of which 5.13% were brain damage or death. Multivariate logistic regression analysis revealed that the ability to perform FONA techniques (odds ratio [OR] 0.23, 95% CI: 0.16, 0.32; P<0.001) and the availability of difficult airway management carts or kits (OR 0.59, 95% CI 0.41, 0.85; P=0.005) were associated with a lower incidence of airway adverse events. CONCLUSIONS: Optical airway devices can overcome some of the challenges posed by difficult airways, yet the CICV scenario remains a major obstacle. The future focus of airway management should be training, particularly for complicated emergency airway techniques.


Assuntos
Manuseio das Vias Aéreas , Humanos , Estudos Transversais , Manuseio das Vias Aéreas/métodos , China , Feminino , Masculino , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/métodos , Adulto , Inquéritos e Questionários
8.
J Pineal Res ; 76(5): e12995, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39073181

RESUMO

Melatonin (MT) has been implicated in the plant response to phosphorus (P) stress; however, the precise molecular mechanisms involved remain unclear. This study investigated whether MT controls internal P distribution and root cell wall P remobilization in rice. Rice was treated with varying MT and P levels and analyzed using biochemical and molecular techniques to study phosphorus utilization. The results demonstrated that low P levels lead to a rapid increase in endogenous MT levels in rice roots. Furthermore, the exogenous application of MT significantly improved rice tolerance to P deficiency, as evidenced by the increased biomass and reduced proportion of roots to shoots under P-deficient conditions. MT application also mitigated the decrease in P content regardless in both the roots and shoots. Mechanistically, MT accelerated the reutilization of P, particularly in the root pectin fraction, leading to increased soluble P liberation. In addition, MT enhanced the expression of OsPT8, a gene involved in root-to-shoot P translocation. Furthermore, we observed that MT induced the production of nitric oxide (NO) in P-deficient rice roots and that the mitigating effect of MT on P deficiency was compromised in the presence of the NO inhibitor, c-PTIO, implying that NO is involved in the MT-facilitated mitigation of P deficiency in rice. Overall, our findings highlight the potential of MT as a promising strategy for enhancing rice tolerance to P deficiency and improving P use efficiency in agricultural practices.


Assuntos
Parede Celular , Melatonina , Óxido Nítrico , Oryza , Fósforo , Raízes de Plantas , Oryza/metabolismo , Fósforo/metabolismo , Melatonina/metabolismo , Melatonina/farmacologia , Raízes de Plantas/metabolismo , Raízes de Plantas/efeitos dos fármacos , Parede Celular/metabolismo , Parede Celular/efeitos dos fármacos , Óxido Nítrico/metabolismo
9.
Int J Ophthalmol ; 17(6): 1094-1101, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895688

RESUMO

AIM: To investigate botulinum toxin A (BTXA) efficacy on small-angle (≤25Δ) acute acquired concomitant esotropia (AACE) in early-stage patients. METHODS: The electronic medical record data of AACE patients during March 2019 and June 2023 were collected in this retrospective and hospital-based cohort study. A total of 72 small-angle AACE patients received BTXA extraocular muscle injection. Patients were grouped by onset-to-treatment time (Group A: ≤6mo, Group B: >6mo). Deviation of esotropia, eye alignment and stereopsis were analyzed at the period of pre/post-injection (1wk, 1, 3, and 6mo). Orthophoria rate at 6mo (horizontal deviation <10Δ and binocular single vision) were considered as outcome index. RESULTS: There were no significant baseline differences (P>0.05) between two groups except onset-to-treatment time (2mo vs 11mo, P<0.001). Higher orthophoria rates were in Group A at last follow-up (94.74% vs 73.53%, P=0.013). Post-BTXA deviations of two groups at 1mo showed no difference (P>0.05); while in 3 and 6mo Group A was significantly smaller than group B (all P<0.001). No statistically significant differences were observed among all post-BTXA deviations of near and distance in Group A. In Group B, deviation at 3mo (near: 2Δ vs 0, P<0.001; distance: 4Δ vs 0, P<0.001) and 6mo (near: 6Δ vs 0, P<0.001; distance: 6Δ vs 0, P<0.001) was significant increased compared to deviation at 1wk after treatment. Group A showed better stereopsis recovery in last follow-up compared to Group B (80″ vs 200″, P=0.002). Both groups obtained improved stereopsis after treatment (Group A: 80″ vs 300″, P<0.001; Group B: 200″ vs 300″, P=0.037). CONCLUSION: BTXA is effective for AACE with small deviation (≤25Δ) in early stage. Delayed treatment (>6mo) may reduce BTXA efficacy. Early BTXA intervention benefits long-term eye alignment and stereopsis recovery.

11.
Ann Surg Open ; 5(2): e429, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38911666

RESUMO

Objective: To determine whether certain patients are vulnerable to errant triage decisions immediately after major surgery and whether there are unique sociodemographic phenotypes within overtriaged and undertriaged cohorts. Background: In a fair system, overtriage of low-acuity patients to intensive care units (ICUs) and undertriage of high-acuity patients to general wards would affect all sociodemographic subgroups equally. Methods: This multicenter, longitudinal cohort study of hospital admissions immediately after major surgery compared hospital mortality and value of care (risk-adjusted mortality/total costs) across 4 cohorts: overtriage (N = 660), risk-matched overtriage controls admitted to general wards (N = 3077), undertriage (N = 2335), and risk-matched undertriage controls admitted to ICUs (N = 4774). K-means clustering identified sociodemographic phenotypes within overtriage and undertriage cohorts. Results: Compared with controls, overtriaged admissions had a predominance of male patients (56.2% vs 43.1%, P < 0.001) and commercial insurance (6.4% vs 2.5%, P < 0.001); undertriaged admissions had a predominance of Black patients (28.4% vs 24.4%, P < 0.001) and greater socioeconomic deprivation. Overtriage was associated with increased total direct costs [$16.2K ($11.4K-$23.5K) vs $14.1K ($9.1K-$20.7K), P < 0.001] and low value of care; undertriage was associated with increased hospital mortality (1.5% vs 0.7%, P = 0.002) and hospice care (2.2% vs 0.6%, P < 0.001) and low value of care. Unique sociodemographic phenotypes within both overtriage and undertriage cohorts had similar outcomes and value of care, suggesting that triage decisions, rather than patient characteristics, drive outcomes and value of care. Conclusions: Postoperative triage decisions should ensure equality across sociodemographic groups by anchoring triage decisions to objective patient acuity assessments, circumventing cognitive shortcuts and mitigating bias.

12.
Artigo em Inglês | MEDLINE | ID: mdl-38922587

RESUMO

In vitro investigations have established metformin's capacity to downregulate PCSK9 expression, suggesting a potential beneficial effect on atherogenic lipoprotein particles when combined with metformin therapy. Our objective was to assess whether metformin could mitigate statin-induced adverse effects on PCSK9, thereby improving lipid profiles in patients with coronary artery disease (CAD) but without diabetes. Employing an open-label, placebo-controlled, randomized trial, we randomized patients with CAD but without diabetes into CLA (Cholesterol-Lowering Agents alone: atorvastatin+/-ezetimibe, n=38) and Met+CLA groups (metformin plus CLA, n=33) at a 1:1 ratio. The primary endpoint was the therapeutic impact of one-month metformin combination treatment on LDL-C and PCSK9 levels. Baseline LDL-C and PCSK9 levels were 76.18 mg·dL-1 and 80.54 ng·mL-1, respectively. After one month, metformin significantly reduced LDL-C (-20.81%, P<0.001), enabling 72% of patients to attain guideline-recommended LDL-C goals. Noteworthy reductions in PCSK9 levels (-15.03%, P<0.001) were observed. Moreover, Met+CLA markedly reduced LDL particle number more than CLA alone (-10.65% vs 1.45%, P=0.009), primarily due to diminished small-dense LDL particle count. Mechanistically, our study demonstrated metformin's inhibition of statin-induced PCSK9 expression in human hepatocellular cells. In summary, a one-month metformin combination regimen reduced LDL-C levels in patients with CAD but without diabetes by inhibiting PCSK9 expression.

13.
Exp Cell Res ; 440(1): 114137, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38897410

RESUMO

Glaucoma is characterized by pathological elevation of intraocular pressure (IOP) due to dysfunctional trabecular meshwork (TM), which is the primary cause of irreversible vision loss. There are currently no effective treatment strategies for glaucoma. Mitochondrial function plays a crucial role in regulating IOP within the TM. In this study, primary TM cells treated with dexamethasone were used to simulate glaucomatous changes, showing abnormal cellular cytoskeleton, increased expression of extracellular matrix, and disrupted mitochondrial fusion and fission dynamics. Furthermore, glaucomatous TM cell line GTM3 exhibited impaired mitochondrial membrane potential and phagocytic function, accompanied by decreased oxidative respiratory levels as compared to normal TM cells iHTM. Mechanistically, lower NAD + levels in GTM3, possibly associated with increased expression of key enzymes CD38 and PARP1 related to NAD + consumption, were observed. Supplementation of NAD + restored mitochondrial function and cellular viability in GTM3 cells. Therefore, we propose that the aberrant mitochondrial function in glaucomatous TM cells may be attributed to increased NAD + consumption dependent on CD38 and PARP1, and NAD + supplementation could effectively ameliorate mitochondrial function and improve TM function, providing a novel alternative approach for glaucoma treatment.


Assuntos
Glaucoma , Mitocôndrias , NAD , Malha Trabecular , Malha Trabecular/metabolismo , Malha Trabecular/efeitos dos fármacos , Malha Trabecular/patologia , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Glaucoma/metabolismo , Glaucoma/patologia , Glaucoma/tratamento farmacológico , NAD/metabolismo , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Pressão Intraocular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , ADP-Ribosil Ciclase 1/metabolismo , ADP-Ribosil Ciclase 1/genética , Linhagem Celular , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli(ADP-Ribose) Polimerase-1/genética , Dexametasona/farmacologia , Células Cultivadas
14.
J Biol Eng ; 18(1): 36, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845032

RESUMO

Exosomes are nanovesicles with multiple components used in several applications. Mesenchymal stem cells (MSCs) are well known for their great potential in clinical applications. MSC-derived exosomes (MSC-Exos) have been shown to mediate tissue regeneration in various diseases, including neurological, autoimmune, and inflammatory diseases, cancer, ischemic heart disease, lung injury, and liver fibrosis. They can modulate the immune response by interacting with immune effector cells in the presence of anti-inflammatory compounds and are involved in intercellular communication through various types of cargo. This review summarizes the MSC-Exos-mediated tissue regeneration in various diseases, including neurological, cardiovascular, liver, kidney, articular cartilage, and oral tissue applications. In addition, we discuss the challenges and prospects of MSC-Exos in tissue regeneration.

15.
Cell Death Dis ; 15(6): 389, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830896

RESUMO

Apolipoprotein O (APOO) plays a critical intracellular role in regulating lipid metabolism. Here, we investigated the roles of APOO in metabolism and atherogenesis in mice. Hepatic APOO expression was increased in response to hyperlipidemia but was inhibited after simvastatin treatment. Using a novel APOO global knockout (Apoo-/-) model, it was found that APOO depletion aggravated diet-induced obesity and elevated plasma cholesterol levels. Upon crossing with low-density lipoprotein receptor (LDLR) and apolipoprotein E (APOE) knockout hyperlipidemic mouse models, Apoo-/- Apoe-/- and Apoo-/- Ldlr-/- mice exhibited elevated plasma cholesterol levels, with more severe atherosclerotic lesions than littermate controls. This indicated the effects of APOO on cholesterol metabolism independent of LDLR and APOE. Moreover, APOO deficiency reduced cholesterol excretion through bile and feces while decreasing phospholipid unsaturation by inhibiting NRF2 and CYB5R3. Restoration of CYB5R3 expression in vivo by adeno-associated virus (AAV) injection reversed the reduced degree of phospholipid unsaturation while decreasing blood cholesterol levels. This represents the first in vivo experimental validation of the role of APOO in plasma cholesterol metabolism independent of LDLR and elucidates a previously unrecognized cholesterol metabolism pathway involving NRF2/CYB5R3. APOO may be a metabolic regulator of total-body cholesterol homeostasis and a target for atherosclerosis management. Apolipoprotein O (APOO) regulates plasma cholesterol levels and atherosclerosis through a pathway involving CYB5R3 that regulates biliary and fecal cholesterol excretion, independently of the LDL receptor. In addition, down-regulation of APOO may lead to impaired mitochondrial function, which in turn aggravates diet-induced obesity and fat accumulation.


Assuntos
Colesterol , Fator 2 Relacionado a NF-E2 , Receptores de LDL , Animais , Receptores de LDL/metabolismo , Colesterol/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos , Camundongos Knockout , Camundongos Endogâmicos C57BL , Metabolismo dos Lipídeos , Masculino , Aterosclerose/metabolismo , Apolipoproteínas/metabolismo , Apolipoproteínas/genética , Humanos , Fígado/metabolismo , Apolipoproteínas E/metabolismo , Hiperlipidemias/metabolismo
17.
Phytomedicine ; 129: 155694, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38733904

RESUMO

BACKGROUND: Ulcerative colitis (UC) is associated with intestinal macrophage infiltration due to disruption of the mucosal barrier and bacterial invasion. Therefore, it is crucial to identify therapeutic agents capable of attenuating the macrophage-induced inflammatory response to preserve mucosal homeostasis and immune tolerance. The modified Zhenwu decoction (CDD-2103) is a novel herbal formulation developed based on the principles of Traditional Chinese medicine. To date, there are no clinically approved herbal formulations for UC with a well-known mechanism of action on macrophages. PURPOSE: The objective of this study was to systematically investigate the inhibitory effect of the active fraction of CDD-2103 in a mouse model of chronic colitis and delineate the mechanisms underlying its inhibitory action. METHODS: CDD-2103 was extracted into four fractions using organic solvents with increasing polarity. A chronic 49-day dextran sulfate sodium (DSS)-induced colitis mice model, closely resembling human clinical conditions, was used to examine the effect of CDD-2103 on chronic colitis. To confirm the effect of CDD-2103 on macrophages in this chronic colitis model, adoptive macrophage transfer and CCL2 supplementation were conducted. The mechanisms of action of CDD-2103 were further elucidated utilizing bone marrow-derived macrophages (BMDMs). Transcriptome analysis was conducted to gain insights into the underlying mechanism of action of CDD-2103 in BMDMs. RESULTS: Our in vitro and in vivo findings demonstrated that the ethanol-enriched fraction of CDD-2103 exhibited significant anti-inflammatory effects, leading to the suppression of colitis severity. This effect was associated with diminished accumulation of colonic macrophages in the lamina propria of CDD-2103-intervened colitis mice. Specifically, CDD-2103 inhibited CCR2/L2-mediated proinflammatory macrophage infiltration into the colon without affecting macrophage proliferation. Mechanistically, CDD-2103 inhibited Fyn expression-mediated p38 MAPK activation and subsequently suppressed CCR2 expression in BMDMs. CONCLUSIONS: Collectively, our study supports the potential use of CDD-2103 to limit macrophage infiltration, thereby reducing inflammation during UC treatment. CDD-2103 and the components in the ethanolic fraction are promising candidates for the development of novel drugs for UC management. Additionally, our study underscores Fyn-mediated CCR2 expression as a potential therapeutic target for the management of UC.


Assuntos
Sulfato de Dextrana , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Macrófagos , Camundongos Endogâmicos C57BL , Receptores CCR2 , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Masculino , Camundongos , Doença Crônica , Colite/tratamento farmacológico , Colite/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Macrófagos/efeitos dos fármacos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Receptores CCR2/metabolismo , Transdução de Sinais/efeitos dos fármacos
18.
Nanoscale ; 16(21): 10448-10457, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38752569

RESUMO

With continuous advances in medical technology, non-invasive embolization has emerged as a minimally invasive treatment, offering new possibilities in cancer therapy. Fluorescent labeling can achieve visualization of therapeutic agents in vivo, providing technical support for precise treatment. This paper introduces a novel in situ non-invasive embolization composite material, Au NPs@(mPEG-PLGTs), created through the electrostatic combination of L-cysteine-modified gold nanoparticles (Au NPs) and methoxy polyethylene glycol amine-poly[(L-glutamic acid)-(L-tyrosine)] (mPEG-PLGTs). Experiments were undertaken to confirm the biocompatibility, degradability, stability and performance of this tumor therapy. The research results demonstrated a reduction in tumor size as early as the fifth day after the initial injection, with a significant 90% shrinkage in tumor volume observed after a 20-day treatment cycle, successfully inhibiting tumor growth and exhibiting excellent anti-tumor effects. Utilizing near-infrared in vivo imaging, Au NPs@(mPEG-PLGTs) displayed effective fluorescence tracking within the bodies of nude BALB-c mice. This study provides a novel direction for the further development and innovation of in situ non-invasive embolization in the field, highlighting its potential for rapid, significant therapeutic effects with minimal invasiveness and enhanced safety.


Assuntos
Ouro , Nanopartículas Metálicas , Camundongos Endogâmicos BALB C , Camundongos Nus , Polietilenoglicóis , Ouro/química , Animais , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Camundongos , Polietilenoglicóis/química , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Embolização Terapêutica , Ácido Poliglutâmico/química , Ácido Poliglutâmico/análogos & derivados
20.
Front Immunol ; 15: 1346587, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38690261

RESUMO

Extracellular vesicles (EVs) are important cell-to-cell communication mediators. This paper focuses on the regulatory role of tumor-derived EVs on macrophages. It aims to investigate the causes of tumor progression and therapeutic directions. Tumor-derived EVs can cause macrophages to shift to M1 or M2 phenotypes. This indicates they can alter the M1/M2 cell ratio and have pro-tumor and anti-inflammatory effects. This paper discusses several key points: first, the factors that stimulate macrophage polarization and the cytokines released as a result; second, an overview of EVs and the methods used to isolate them; third, how EVs from various cancer cell sources, such as hepatocellular carcinoma, colorectal carcinoma, lung carcinoma, breast carcinoma, and glioblastoma cell sources carcinoma, promote tumor development by inducing M2 polarization in macrophages; and fourth, how EVs from breast carcinoma, pancreatic carcinoma, lungs carcinoma, and glioblastoma cell sources carcinoma also contribute to tumor development by promoting M2 polarization in macrophages. Modified or sourced EVs from breast, pancreatic, and colorectal cancer can repolarize M2 to M1 macrophages. This exhibits anti-tumor activities and offers novel approaches for tumor treatment. Therefore, we discovered that macrophage polarization to either M1 or M2 phenotypes can regulate tumor development. This is based on the description of altering macrophage phenotypes by vesicle contents.


Assuntos
Vesículas Extracelulares , Ativação de Macrófagos , Macrófagos , Neoplasias , Animais , Humanos , Comunicação Celular/imunologia , Citocinas/metabolismo , Vesículas Extracelulares/imunologia , Vesículas Extracelulares/metabolismo , Ativação de Macrófagos/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Neoplasias/imunologia , Neoplasias/terapia , Neoplasias/patologia , Neoplasias/metabolismo , Microambiente Tumoral/imunologia
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