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1.
Int J Mol Sci ; 25(13)2024 Jun 30.
Article de Anglais | MEDLINE | ID: mdl-39000343

RÉSUMÉ

Mesenchymal stem cells (MSCs) have shown great potential for the treatment of liver injuries, and the therapeutic efficacy greatly depends on their homing to the site of injury. In the present study, we detected significant upregulation of hepatocyte growth factor (HGF) in the serum and liver in mice with acute or chronic liver injury. In vitro study revealed that upregulation of miR-9-5p or miR-221-3p promoted the migration of human MSCs (hMSCs) toward HGF. Moreover, overexpression of miR-9-5p or miR-221-3p promoted hMSC homing to the injured liver and resulted in significantly higher engraftment upon peripheral infusion. hMSCs reduced hepatic necrosis and inflammatory infiltration but showed little effect on extracellular matrix (ECM) deposition. By contrast, hMSCs overexpressing miR-9-5p or miR-221-3p resulted in not only less centrilobular necrosis and venous congestion but also a significant reduction of ECM deposition, leading to obvious improvement of hepatocyte morphology and alleviation of fibrosis around central vein and portal triads. Further studies showed that hMSCs inhibited the activation of hepatic stellate cells (HSCs) but could not decrease the expression of TIMP-1 upon acute injury and the expression of MCP-1 and TIMP-1 upon chronic injury, while hMSCs overexpressing miR-9-5p or miR-221-3p led to further inactivation of HSCs and downregulation of all three fibrogenic and proinflammatory factors TGF-ß, MCP-1, and TIMP-1 upon both acute and chronic injuries. Overexpression of miR-9-5p or miR-221-3p significantly downregulated the expression of α-SMA and Col-1α1 in activated human hepatic stellate cell line LX-2, suggesting that miR-9-5p and miR-221-3p may partially contribute to the alleviation of liver injury by preventing HSC activation and collagen expression, shedding light on improving the therapeutic efficacy of hMSCs via microRNA modification.


Sujet(s)
Cellules étoilées du foie , Transplantation de cellules souches mésenchymateuses , Cellules souches mésenchymateuses , microARN , microARN/génétique , microARN/métabolisme , Humains , Cellules souches mésenchymateuses/métabolisme , Cellules étoilées du foie/métabolisme , Animaux , Souris , Transplantation de cellules souches mésenchymateuses/méthodes , Lésions hépatiques dues aux substances/métabolisme , Lésions hépatiques dues aux substances/thérapie , Lésions hépatiques dues aux substances/génétique , Mâle , Tétrachloro-méthane/effets indésirables , Facteur de croissance des hépatocytes/métabolisme , Facteur de croissance des hépatocytes/génétique , Souris de lignée C57BL , Mouvement cellulaire
2.
Org Lett ; 2024 Jul 11.
Article de Anglais | MEDLINE | ID: mdl-38989859

RÉSUMÉ

A novel Ag-catalyzed ring opening of unsymmetric cyclopropenones for the stereoselective synthesis of a diverse range of α-alkylidene lactones has been developed. In this protocol, two different C-C(O) bonds were distinguished, demonstrating selective C-C bond activation. This reaction features a wide substrate scope, good functional group compatibility, and high atom economy, providing a versatile and general approach to the construction of α-alkylidene lactones.

3.
Ther Drug Monit ; 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38967521

RÉSUMÉ

BACKGROUND: To determine the associations among self-reported vitamin D (VD) supplementation, measured serum 25-hydroxyvitamin D (25[OH]D) concentrations, and all-cause and cause-specific mortality risks. METHODS: Self-reported VD supplementation, serum 25(OH)D concentration, and all-cause and cause-specific mortality data from the National Health and Nutrition Examination Survey 2007-2018 were examined for 10,793 adults ≥20 years from the United States. VD dosage was categorized as <800 or ≥800 IU/d. The mortality status and causes of mortality up to 2019 were determined using the National Death Index. The relationships among VD, 25(OH)D levels, and mortality were analyzed using Cox regression before and after propensity score matching (PSM). RESULTS: Over a median of 6.6 years, 915 deaths were recorded, 230 because of cardiovascular disease (CVD), 240 because of cancer, and 445 because of other specific causes. Mortality risk did not differ between VD <800 IU/d and ≥800 IU/d before or after PSM. However, serum 25(OH)D concentrations were statistically different before and after PSM. The upper 2 quartiles of 25(OH)D levels were associated with lower all-cause mortality, and the fourth quartile was associated with reduced other-specific mortality before and after PSM. No correlation was found between the 25(OH)D concentration and CVD- or cancer-specific mortality after PSM. The inverse 25(OH)D-mortality relationship was consistent across subgroups. CONCLUSIONS: Based on this large cohort study, higher 25(OH)D levels are robustly associated with reduced all-cause and other specific mortality but not CVD- or cancer-specific mortality. These findings support the benefits of maintaining adequate VD status for longevity. Further research is required to elucidate these mechanisms and define the optimal VD concentration to reduce mortality. These results underscore the importance of public health strategies for preventing VD deficiency.

4.
Ann Am Thorac Soc ; 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38959407

RÉSUMÉ

RATIONALE: Home mechanical ventilation (HMV) is an advanced medical therapy offered to children with medical complexity. Despite the growing pediatric HMV population in North America, there are limited studies describing healthcare utilization and predictors of highest costs using robust health administrative data. OBJECTIVES: To describe patterns of healthcare utilization and costs in children receiving HMV over a 14-year period in Ontario, Canada. METHODS: We conducted a retrospective population-based cohort study (April 1, 2003 to March 31, 2017) of children aged 0-18 years receiving HMV via invasive mechanical ventilation (IMV) or non-invasive ventilation (NIV). Paired t-tests compared healthcare system utilization and costs two years before and two years after HMV approval. We developed linear models to analyze variables associated with children in the top quartile of health service utilization and costs. RESULTS: We identified 835 children receiving HMV. In the two years after HMV approval compared to the 2 years prior, children had decreased hospitalization days (median 9 (IQR 3-30) versus 29 (6-99), p<0.0001) and ICU admission days (6.6 (1.9-18.0) versus 17.1 (3.3-70.9), p<0.0001) but had increased homecare service approvals (195 (24-522) versus 40 (12-225), p<0.0001) and outpatient Pulmonology visits (3 (1-4) versus 2 (1-3), p<0.0001). Total healthcare costs were higher in the two years after HMV approval (mean $164,892 (SD $214,187) versus $128,941 ($194,199), p<0.0001). However, all-cause hospital admission costs were reduced ($66,546 ($142,401) versus $81,578 ($164,672), p<0.0001). Highest total 2-year costs were associated with IMV (OR 3.45, 95% CI 2.24-5.31; reference NIV), number of medical devices at home (OR 1.63, 95% CI 1.35-1.96; reference no technology), and increased healthcare costs in the year prior to HMV initiation (OR 2.23, 95% CI 1.84-2.69). CONCLUSIONS: Children progressing to the need for HMV represent a worsening in their respiratory status that will undoubtedly increase healthcare utilization and costs. We found that the initiation of HMV in these children can reduce inpatient healthcare utilization and costs but can still increase overall healthcare expenditures, especially in the outpatient setting.

5.
J Sci Food Agric ; 2024 Jul 03.
Article de Anglais | MEDLINE | ID: mdl-38961686

RÉSUMÉ

Hyacinth bean [Lablab purpureus (L.) Sweet], a plant belonging to the leguminous family and traditionally used for medicinal purposes in China, is a valuable resource with a wide range of health benefits. This review examines the bioactive compounds, health-promoting properties and functional food potential of hyacinth bean, highlighting its role in protecting against metabolic diseases and the underlying molecular mechanisms. According to existing research, hyacinth bean contains a diverse array of bioactive compounds, Consumption of hyacinth beans and hyacinth bean-related processed food products, as well as their use in medicines, is associated with a variety of health benefits that are increasingly favoured by the scientific community. In light of these findings, we posit that hyacinth bean holds great promise for further research and food application. © 2024 Society of Chemical Industry.

6.
Sci Total Environ ; 943: 173727, 2024 Sep 15.
Article de Anglais | MEDLINE | ID: mdl-38839016

RÉSUMÉ

Vegetation dynamics is essential for characterizing surface biogeophysical parameters. Speeds of vegetation development and senescence are well documented, however, the effects of vegetation growth rates on surface parameters during different growth stages remains unclear. By using such methods as trend analyses and correlation analyses, this study examines the variations and interactive relationships of leaf area index (LAI) and surface parameters including Albedo, evapotranspiration (ET), and land surface temperature (LST), derived from Moderate Resolution Imaging Spectroradiometer (MODIS), during the intra-growing season (April-October, GS) on the Mongolian Plateau (MP). Generally, LAI exhibited a significant upward trend across GS months. Significant changes in VLAI (the difference in LAI between 2 consecutive months) in April-May and September-October indicated that the vegetation change rates were accelerated in the early GS (April-June) and late GS (September-October). The effect of vegetation activity on surface parameters varies over time and space. The effects of VLAI on the speed of surface parameters were inconsistent during the intra-GS. As a result of the significant changes in LAI, VET (the difference in ET between 2 consecutive months) displayed a significant upward trend during the early GS but a significant downward trend during the late GS. With acceleration of vegetation activity, the effects of VET and VAlbedo (the difference in Albedo between 2 consecutive months) on LST could offset each other at different stages of the GS. In addition, the effect of VLAI on the speed of surface parameters varied significantly by vegetation types. Our findings imply that clarifying the impact of vegetation activity on surface parameters at different growth stages can advance our understanding of vegetation responses and feedbacks to climate change.


Sujet(s)
Développement des plantes , Mongolie , Saisons , Surveillance de l'environnement , Température , Écosystème , Feuilles de plante/croissance et développement , Plantes , Changement climatique
7.
Front Mol Biosci ; 11: 1410004, 2024.
Article de Anglais | MEDLINE | ID: mdl-38855325

RÉSUMÉ

Identification of novel therapeutic targets for type 2 diabetes is a key area of contemporary research. In this study, we screened differentially expressed genes in type 2 diabetes through the GEO database and sought to identify the key virulence factors for type 2 diabetes through a transcription factor regulatory network. Our findings may help identify new therapeutic targets for type 2 diabetes. Data pertaining to the humoral (whole blood) gene expression profile of diabetic patients were obtained from the NCBI's GEO Datasets database and gene sets with differential expression were identified. Subsequently, the TRED transcriptional regulatory element database was integrated to build a gene regulatory network for type 2 diabetes. Functional analysis (GO-Analysis) and Pathway-analysis of differentially expressed genes were performed using the DAVID database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Finally, gene-disease correlation analysis was performed using the DAVID online annotation tool. A total of 236 pathogenic genes, four transcription factors related to the pathogenic genes, and 261 corresponding target genes were identified. A transcription factor-target gene regulatory network for type 2 diabetes was constructed. Most of the key factors of the transcription factor-target gene regulatory network for type 2 diabetes were found closely related to the immune metabolic system and the functions of cell proliferation and transformation.

8.
Plant Commun ; : 100999, 2024 Jun 08.
Article de Anglais | MEDLINE | ID: mdl-38853433

RÉSUMÉ

Grain weight, a key determinant of yield in rice (Oryza sativa L.), is governed primarily by genetic factors, whereas grain chalkiness, a detriment to grain quality, is intertwined with environmental factors such as mineral nutrients. Nitrogen (N) is recognized for its impact on grain chalkiness, yet the underlying molecular mechanisms remain elusive. This study revealed the pivotal role of rice NODULE INCEPTION-LIKE PROTEIN 3 (OsNLP3) in simultaneously regulating grain weight and grain chalkiness. Our investigation showed that the loss of OsNLP3 leads to a reduction in both grain weight and dimension, in contrast to the enhancement observed with OsNLP3 overexpression. OsNLP3 directly suppresses the expression of OsCEP6.1 and OsNF-YA8, which were identified as negative regulators associated with grain weight. Consequently, two novel regulatory modules, OsNLP3-OsCEP6.1 and OsNLP3-OsNF-YA8, were identified as key players in grain weight regulation. Notably, the OsNLP3-OsNF-YA8 module not only augments grain weight but also mitigates grain chalkiness in response to N. This research clarifies the molecular mechanisms orchestrating grain weight through the OsNLP3-OsCEP6.1 and OsNLP3-OsNF-YA8 modules, underscoring the pivotal role of the OsNLP3-OsNF-YA8 module in alleviating grain chalkiness. These findings offer potential targets for concurrently enhancing rice yield and quality.

9.
Arch Rheumatol ; 39(2): 213-220, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38933718

RÉSUMÉ

Objectives: This study aimed to analyze the risk factors for mortality of idiopathic inflammatory myopathy (IIM) patients admitted with interstitial lung disease (ILD) to guide rapid and accurate judgment of clinical prognosis. Patients and methods: This retrospective, single-center cohort study was conducted with 135 participants (37 males, 98 females; mean age: 54.8±11.1 years; range, 24 to 85 years) between June 1, 2016, and June 30, 2021. The participants were categorized into the survival group (n=111) and nonsurvivors (n=24) according to whether they survived during the one-year follow-up. The independent risk factors for mortality in one year after discharge were analyzed. Receiver operating characteristic curve analysis was used to determine the accuracy of oxygenation index at baseline combined with pulmonary infection (PI) at follow-up to indicate death in IIM-ILD patients. Results: Compared to the survival group, nonsurvivors were older (p=0.006) and had a higher proportion of anti-MDA5 (melanoma differentiation-associated protein 5) positivity (p<0.001). The ILD duration was shorter (p=0.006), the oxygenation index was lower (p<0.001), and the intensive care unit occupancy rate (p<0.001) and ventilator utilization rate (p<0.001) were elevated in nonsurvivors compared to the survival group. Oxygenation index at baseline (odds ratio [OR]=1.021, 95% confidence interval [CI]: 1.001-1.023, p=0.040) and PI (clinical judgment) at follow-up (OR=16.471, 95% CI: 1.565-173.365, p=0.020) were found as independent risk factors for death in the year after discharge in IIM inpatients with ILD. An oxygenation index ≤279 mmHg at baseline combined with PI at follow-up exhibited a promising predictive value for all-cause death in IIM-ILD patients within one year. Conclusion: Oxygenation index at baseline and PI during follow-up were independent risk factors for death of IIM-ILD patients within one year after discharge. Patients with an oxygenation index ≤279 mmHg at baseline had an increased risk of death once they developed PI during the one-year follow-up.

10.
Poult Sci ; 103(8): 103896, 2024 May 23.
Article de Anglais | MEDLINE | ID: mdl-38889568

RÉSUMÉ

In recent years, a series of public health issues caused by the spread of antibiotic resistance have been widely concerned. The indoor air of livestock and poultry houses is considered to be one of the main sources of environmental contamination of ARGs. This study characterized the micro-organisms and ARGs in the air particulate matter of chicken houses using metagenomics. The study successfully detected 761 different subtypes of resistance genes including aminoglycosides, tetracyclines, MLSB etc., 4 types of mobile genetic elements, and various pathogenic microorganisms from the aerosols in the chicken coop environment. The results showed that the abundance of ARGs in the air of the chicken coop was at a relatively high level, correlation network analysis showed that multiple types of ARGs could promote the emergence of antibiotic-resistant bacteria.

11.
Immun Inflamm Dis ; 12(6): e1333, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38934407

RÉSUMÉ

BACKGROUND: Particulate ß-glucans (WGP) are natural compounds with regulatory roles in various biological processes, including tumorigenesis and inflammatory diseases such as allergic asthma. However, their impact on mast cells (MCs), contributors to airway hyperresponsiveness (AHR) and inflammation in asthma mice, remains unknown. METHODS: C57BL/6 mice underwent repeated OVA sensitization without alum, followed by Ovalbumin (OVA) challenge. Mice received daily oral administration of WGP (OAW) at doses of 50 or 150 mg/kg before sensitization and challenge. We assessed airway function, lung histopathology, and pulmonary inflammatory cell composition in the airways, as well as proinflammatory cytokines and chemokines in the bronchoalveolar lavage fluid (BALF). RESULTS: The 150 mg/kg OAW treatment mitigated OVA-induced AHR and airway inflammation, evidenced by reduced airway reactivity to aerosolized methacholine (Mch), diminished inflammatory cell infiltration, and goblet cell hyperplasia in lung tissues. Additionally, OAW hindered the recruitment of inflammatory cells, including MCs and eosinophils, in lung tissues and BALF. OAW treatment attenuated proinflammatory tumor necrosis factor (TNF)-α and IL-6 levels in BALF. Notably, OAW significantly downregulated the expression of chemokines CCL3, CCL5, CCL20, CCL22, CXCL9, and CXCL10 in BALF. CONCLUSION: These results highlight OAW's robust anti-inflammatory properties, suggesting potential benefits in treating MC-dependent AHR and allergic inflammation by influencing inflammatory cell infiltration and regulating proinflammatory cytokines and chemokines in the airways.


Sujet(s)
Asthme , Modèles animaux de maladie humaine , Mastocytes , Souris de lignée C57BL , bêta-Glucanes , Animaux , Asthme/immunologie , Asthme/traitement médicamenteux , Asthme/anatomopathologie , Mastocytes/immunologie , Mastocytes/effets des médicaments et des substances chimiques , Mastocytes/métabolisme , Souris , Administration par voie orale , bêta-Glucanes/pharmacologie , bêta-Glucanes/administration et posologie , Cytokines/métabolisme , Inflammation/traitement médicamenteux , Inflammation/immunologie , Ovalbumine/immunologie , Hypersensibilité respiratoire/traitement médicamenteux , Hypersensibilité respiratoire/immunologie , Liquide de lavage bronchoalvéolaire/immunologie , Poumon/immunologie , Poumon/anatomopathologie , Poumon/effets des médicaments et des substances chimiques
12.
Adv Sci (Weinh) ; : e2400493, 2024 Jun 18.
Article de Anglais | MEDLINE | ID: mdl-38894572

RÉSUMÉ

Non-alcoholic fatty liver disease (NAFLD) is a prominent cause of various chronic metabolic hepatic diseases with limited therapeutics. Rubicon, an essential regulator in lysosomal degradation, is reported to exacerbate hepatic steatosis in NAFLD mice and patients, indicating its probability of being a therapeutic target for NAFLD treatment. In this study, the therapeutic potential of Rubicon blockage is investigated. Lipid nanoparticles carrying Rubicon-specific CRISPR-Cas9 components exhibited liver accumulation, cell internalization, and Rubicon knockdown. A single administration of the nanoparticles results in attenuated lipid deposition and hepatic steatosis, with lower circulating lipid levels and decreased adipocyte size in NAFLD mice. Furthermore, the increase of phosphatidylcholine and phosphatidylethanolamine levels can be observed in the NAFLD mice livers after Rubicon silencing, along with regulatory effects on metabolism-related genes such as CD36, Gpcpd1, Chka, and Lpin2. The results indicate that knockdown of Rubicon improves glycerophospholipid metabolism and thereby ameliorates the NAFLD progression, which provides a potential strategy for NAFLD therapy via the restoration of Rubicon.

15.
Cell Biol Int ; 48(8): 1111-1123, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38741282

RÉSUMÉ

Polycystic ovary syndrome (PCOS) is the primary cause of female infertility with a lack of universal therapeutic regimen. Although osthole exhibits numerous pharmacological activities in treating various diseases, its therapeutic effect on PCOS is undiscovered. The present study found that application of osthole improved the symptoms of PCOS mice through preventing ovarian granulosa cells (GCs) production of more estrogen and alleviating the liberation of pro-inflammatory cytokine interleukin (IL)-1ß, IL-6, and tumor necrosis factor alpha. Meanwhile, osthole enhanced ovarian antioxidant capacity and alleviated intracellular reactive oxygen species (ROS) accumulation with a concurrent attenuation for oxidative stress, while intervention of antioxidant enzymic activity and glutathione (GSH) synthesis neutralized the salvation of osthole on GCs secretory disorder and chronic inflammation. Further analysis revealed that osthole restored the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and forkhead box O 1 (Foxo1) whose repression antagonized the amelioration of osthole on the insufficiency of antioxidant capacity and accumulation of ROS. Moreover, Nrf2 served as an intermedium to mediate the regulation of osthole on Foxo1. Additionally, osthole restricted the phosphorylation of IκBα and nuclear factor kappa B (NF-κB) subunit p65 by DHEA and weakened the transcriptional activity of NF-κB, but this effectiveness was abrogated by the obstruction of Nrf2 and Foxo1, whereas adjunction of GSH renewed the redemptive effect of osthole on NF-κB whose activation caused an invalidation of osthole in rescuing the aberration of GCs secretory function and inflammation response. Collectively, osthole might relieve the symptoms of PCOS mice via Nrf2-Foxo1-GSH-NF-κB pathway.


Sujet(s)
Coumarines , Protéine O1 à motif en tête de fourche , Glutathion , Facteur-2 apparenté à NF-E2 , Facteur de transcription NF-kappa B , Stress oxydatif , Syndrome des ovaires polykystiques , Espèces réactives de l'oxygène , Transduction du signal , Animaux , Syndrome des ovaires polykystiques/métabolisme , Syndrome des ovaires polykystiques/traitement médicamenteux , Femelle , Facteur-2 apparenté à NF-E2/métabolisme , Souris , Coumarines/pharmacologie , Coumarines/usage thérapeutique , Facteur de transcription NF-kappa B/métabolisme , Protéine O1 à motif en tête de fourche/métabolisme , Transduction du signal/effets des médicaments et des substances chimiques , Glutathion/métabolisme , Stress oxydatif/effets des médicaments et des substances chimiques , Espèces réactives de l'oxygène/métabolisme , Antioxydants/pharmacologie , Cellules de la granulosa/métabolisme , Cellules de la granulosa/effets des médicaments et des substances chimiques , Modèles animaux de maladie humaine
16.
Expert Rev Vaccines ; 23(1): 570-583, 2024.
Article de Anglais | MEDLINE | ID: mdl-38733272

RÉSUMÉ

INTRODUCTION: The mRNA vaccine technologies have progressed rapidly in recent years. The COVID-19 pandemic has accelerated the application of mRNA vaccines, with research and development and clinical trials underway for many vaccines. Application of the quality by design (QbD) framework to mRNA vaccine development and establishing standardized quality control protocols for mRNA vaccines are essential for the continued development of high-quality mRNA vaccines. AREAS COVERED: mRNA vaccines include linear mRNA, self-amplifying mRNA, and circular RNA vaccines. This article summarizes the progress of research on quality control of these three types of vaccines and presents associated challenges and considerations. EXPERT OPINION: Although there has been rapid progress in research on linear mRNA vaccines, their degradation patterns remain unclear. In addition, standardized assays for key impurities, such as residual dsRNA and T7 RNA polymerase, are still lacking. For self-amplifying mRNA vaccines, a key focus should be control of stability in vivo and in vitro. For circular RNA vaccines, standardized assays, and reference standards for determining degree of circularization should be established and optimized.


Sujet(s)
Vaccins contre la COVID-19 , COVID-19 , Contrôle de qualité , Vaccins à ARNm , Humains , Vaccins contre la COVID-19/immunologie , Vaccins contre la COVID-19/administration et posologie , Vaccins contre la COVID-19/normes , COVID-19/prévention et contrôle , Vaccins synthétiques/immunologie , Vaccins synthétiques/administration et posologie , Développement de vaccin , Animaux , ARN messager/génétique , ARN messager/immunologie , SARS-CoV-2/immunologie , SARS-CoV-2/génétique
17.
Cell Mol Immunol ; 21(6): 620-633, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38720063

RÉSUMÉ

Peptidyl arginine deiminase 4 (PAD4) plays a pivotal role in infection and inflammatory diseases by facilitating the formation of neutrophil extracellular traps (NETs). However, the substrates of PAD4 and its exact role in inflammatory bowel disease (IBD) remain unclear. In this study, we employed single-cell RNA sequencing (scRNA-seq) and substrate citrullination mapping to decipher the role of PAD4 in intestinal inflammation associated with IBD. Our results demonstrated that PAD4 deficiency alleviated colonic inflammation and restored intestinal barrier function in a dextran sulfate sodium (DSS)-induced colitis mouse model. scRNA-seq analysis revealed significant alterations in intestinal cell populations, with reduced neutrophil numbers and changes in epithelial subsets upon PAD4 deletion. Gene expression analysis highlighted pathways related to inflammation and epithelial cell function. Furthermore, we found that neutrophil-derived extracellular vesicles (EVs) carrying PAD4 were secreted into intestinal epithelial cells (IECs). Within IECs, PAD4 citrullinates mitochondrial creatine kinase 1 (CKMT1) at the R242 site, leading to reduced CKMT1 protein stability via the autophagy pathway. This action compromises mitochondrial homeostasis, impairs intestinal barrier integrity, and induces IECs apoptosis. IEC-specific depletion of CKMT1 exacerbated intestinal inflammation and apoptosis in mice with colitis. Clinical analysis of IBD patients revealed elevated levels of PAD4, increased CKMT1 citrullination, and decreased CKMT1 expression. In summary, our findings highlight the crucial role of PAD4 in IBD, where it modulates IECs plasticity via CKMT1 citrullination, suggesting that PAD4 may be a potential therapeutic target for IBD.


Sujet(s)
Citrullination , Inflammation , Maladies inflammatoires intestinales , Muqueuse intestinale , Souris de lignée C57BL , Granulocytes neutrophiles , Protein-arginine deiminase Type 4 , Animaux , Humains , Mâle , Souris , Colite/anatomopathologie , Colite/induit chimiquement , Sulfate dextran , Modèles animaux de maladie humaine , Inflammation/anatomopathologie , Maladies inflammatoires intestinales/anatomopathologie , Muqueuse intestinale/anatomopathologie , Muqueuse intestinale/métabolisme , Souris knockout , Granulocytes neutrophiles/métabolisme , Granulocytes neutrophiles/immunologie , Protein-arginine deiminase Type 4/métabolisme , Creatine kinase/métabolisme
18.
J Agric Food Chem ; 72(23): 13015-13022, 2024 Jun 12.
Article de Anglais | MEDLINE | ID: mdl-38807413

RÉSUMÉ

The extensive and repeated application of chemical fungicides results in the rapid development of fungicide resistance. Novel antifungal pesticides are urgently required. Natural products have been considered precious sources of pesticides. It is necessary to discover antifungal pesticides by using natural products. Herein, 42 various griseofulvin derivatives were synthesized. Their antifungal activities were evaluated in vitro. Most of them showed good antifungal activity, especially 3d exhibited a very broad antifungal spectrum and the most significant activities against 7 phytopathogenic fungi. In vivo activity results suggested that 3d protected apples and tomatoes from serious infection by phytopathogenic fungi. These proved that 3d had the potential to be a natural product-derived antiphytopathogenic fungi agent. Furthermore, docking analysis suggested that tubulin might be one of the action sites of 3d. It is reasonable to believe that griseofulvin derivatives are worth further development for the discovery of new pesticides.


Sujet(s)
Champignons , Fongicides industriels , Griséofulvine , Maladies des plantes , Griséofulvine/pharmacologie , Griséofulvine/composition chimique , Griséofulvine/synthèse chimique , Fongicides industriels/pharmacologie , Fongicides industriels/synthèse chimique , Fongicides industriels/composition chimique , Maladies des plantes/microbiologie , Relation structure-activité , Champignons/effets des médicaments et des substances chimiques , Simulation de docking moléculaire , Solanum lycopersicum/microbiologie , Tests de sensibilité microbienne , Structure moléculaire , Antifongiques/pharmacologie , Antifongiques/synthèse chimique , Antifongiques/composition chimique
19.
J Colloid Interface Sci ; 671: 336-343, 2024 Oct.
Article de Anglais | MEDLINE | ID: mdl-38815370

RÉSUMÉ

Against the backdrop of advancements in modern multifunctional wearable electronics, there is a growing demand for simple, sustainable, and portable electronic skin (e-skin), posing significant challenges. This study aims to delineate the development of a straightforward, transparent, highly sensitive, and high power-density electronic skin based on a triboelectric nanogenerator(S-TENG), designed for harvesting human body energy and real-time monitoring of the physiological motion status. Our e-skin incorporates thermally treated polyvinylidene fluoride (PVDF) fiber membranes as the contact layer and a film of silver nanowires as the conductive electrodes. The resulting contact-separation type e-skin exhibits an impressive transparency of 80 %, along with a nice sensitivity value, capable of detecting a light touch from a 0.13 g sponge and demonstrating good working stability and breathability. Leveraging the triboelectric effect, our e-skin generates an open-circuit voltage of 301 V and a short-circuit current of 2.7 µA under an extrinsic force of 8 N over an interaction area of 4 × 4 cm2, achieving a power density up to 306 mW/m2. With its signal processing circuitry, the integrated S-TENG showcases nice energy harvesting and signal transmission capabilities. Accordingly, we contend that S-TENG has potential applications in energy capture and real-time human motion state monitoring. This research is anticipated to blaze a novel and practical trail for self-powered wearable devices and personalized health rehabilitation training regimens.


Sujet(s)
Alimentations électriques , Dispositifs électroniques portables , Humains , Nanotechnologie , Monitorage physiologique/instrumentation , Monitorage physiologique/méthodes , Nanofils/composition chimique , Argent/composition chimique , Polyvinyles/composition chimique , Électrodes , Propriétés de surface , Tests d'analyse de l'haleine/instrumentation , Polymères de fluorocarbone
20.
J Food Sci ; 89(6): 3700-3712, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38709880

RÉSUMÉ

The densified powder material is convenient for storage and transportation, with broad market application prospects. In this study, the discrete element model parameters required for simulating gluten densification were calibrated using the Hertz-Mindlin with JKR contact model. Initially, physical testing techniques were utilized to assess the size distribution, density, and angle of repose (AoR) of gluten particles. Following this, the Plackett-Burman test, the steepest ascent test, and the Box-Behnken test were conducted, and the significant factors were obtained: The coefficient of rolling friction (P-P) was 1.038, the coefficient of static friction (P-P) was 0.071, and the surface energy (P-P) was 0.047. Finally, the AoR and densification simulations were performed under the optimal parameter combination, along with validation tests. The results showed that the relative error between the simulated and tested AoR was 0.52%. The compression ratio and compression force curves of simulated and actual were similar.


Sujet(s)
Glutens , Glutens/composition chimique , Glutens/analyse , Calibrage , Poudres/composition chimique , Manipulation des aliments/méthodes , Taille de particule , Friction , Modèles théoriques
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