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1.
Biomed Mater ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38574669

RESUMO

Recently, in vitro models of intestinal mucosa have become important tools for drug screening and studying the physiology and pathology of the intestine. These models enable the examination of cellular behavior in diseased states or in reaction to alterations in the microenvironment, potentially serving as alternatives to animal models. One of the major challenges in constructing physiologically relevant in vitro models of intestinal mucosa is the creation of three-dimensional (3D) microstructures that accurately mimic the integration of intestinal epithelium and vascularized stroma. Here, core-shell alginate (Alg) microspheres were generated to create the compartmentalized extracellular matrix (ECM) microenvironment needed to simulate the epithelial and vascularized stromal compartments of the intestinal mucosa. We demonstrated that NIH-3T3 and human umbilical vein endothelial cells (HUVECs) embedded in the core of the microspheres can proliferate and develop a vascular network, while human colorectal adenocarcinoma cells (Caco-2) can form an epithelial monolayer in the shell. Compared to Caco-2 monolayer encapsulated within the shell, the presence of the vascularized stroma enhances their proliferation and functionality. As such, our core-shell Alg microspheres provide a valuable method for generating in vitro models of vascularized intestinal mucosa with epithelial and vascularized stroma arranged in a spatially relevant manner and demonstrating near-physiological functionality.

2.
Nat Mater ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38594486

RESUMO

DNA origami is capable of spatially organizing molecules into sophisticated geometric patterns with nanometric precision. Here we describe a reconfigurable, two-dimensional DNA origami with geometrically patterned CD95 ligands that regulates immune cell signalling to alleviate rheumatoid arthritis. In response to pH changes, the device reversibly transforms from a closed to an open configuration, displaying a hexagonal pattern of CD95 ligands with ~10 nm intermolecular spacing, precisely mirroring the spatial arrangement of CD95 receptor clusters on the surface of immune cells. In a collagen-induced arthritis mouse model, DNA origami elicits robust and selective activation of CD95 death-inducing signalling in activated immune cells located in inflamed synovial tissues. Such localized immune tolerance ameliorates joint damage with no noticeable side effects. This device allows for the precise spatial control of cellular signalling, expanding our understanding of ligand-receptor interactions and is a promising platform for the development of pharmacological interventions targeting these interactions.

4.
Front Cardiovasc Med ; 11: 1335912, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38440209

RESUMO

We report a 42-year-old male patient who was diagnosed with acute myocardial infarction (AMI), and subsequently underwent percutaneous coronary intervention (PCI) for revascularization. The patient was transferred to the cardiac intensive care unit for intra-aortic balloon pump (IABP) due to frequent malignant arrhythmia after PCI. Then the patient experienced the most severe complications of IABP, including multiple organ embolism and intestinal necrosis. This report highlights the rare serious complications of IABP and the challenges encountered in handling this complex case.

5.
Sci Total Environ ; 921: 171078, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38382615

RESUMO

Decreased snow depth resulting from global warming has the potential to significantly impact biogeochemical cycles in cold forests. However, the specific mechanisms of how snow reduction affects litter decomposition and the underlying microbial processes remain unclear, this knowledge gap limits our ability to precisely predict ecological processes within cold forest ecosystems under climate change. Hence, a field experiment was conducted in a subalpine forest in southwestern China, involving a gradient of snow reduction levels (control, 50 %, 100 %) to investigate the effects of decreased snow on litter decomposition, as well as microbial biomass and activity, specifically focused on two common species: red birch (Betula albosinensis) and masters larch (Larix mastersiana). After one year of incubation, the decomposition rate (k-value) of the two types of litter ranged from 0.12 to 0.24 across three snow treatments. A significant lower litter mass loss, microbial biomass and enzyme activity were observed under decreased snow depth in winter. Furthermore, a hysteresis inhibitory effect of snow reduction on hydrolase activity was observed in the following growing season. Additionally, the high initial quality (lower C/N ratio) of red birch litter facilitated the colonization by a greater quantity of microorganisms, making it more susceptible to snow reduction compared to the low-quality masters larch litter. Structural equation models indicated that decreased snow depth hindered litter decomposition by altering the biological characterization of litter (e.g., microbial biomass and enzyme activity) and environmental variables (e.g., mean temperature and moisture content). The findings suggest that the potential decline in snow depth could inhibit litter decomposition by reducing microbial biomass and activity, implying that the future climate change may alter the material cycling processes in subalpine forest ecosystems.


Assuntos
Ecossistema , Neve , Biomassa , Florestas , China , Folhas de Planta/química , Solo/química
6.
ACS Appl Mater Interfaces ; 16(9): 11251-11262, 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38394459

RESUMO

Nanozyme has been proven to be an attractive and promising candidate to alleviate the current pressing medical problems. However, the unknown clinical safety and limited function beyond the catalysis of the most reported nanozymes cannot promise an ideal therapeutic outcome in further clinical application. Herein, we find that ferric maltol (FM), a clinically approved iron supplement synthesized through a facile scalable method, exhibits excellent peroxidase-like activity than natural horseradish peroxidase-like (HRP) and commonly reported Fe-based nanozymes, and also shows high antibacterial performance for methicillin-resistant Staphylococcus aureus (MRSA) elimination (100%) and wound disinfection. In addition, with added effects inherited from contained maltol, FM can accelerate skin barrier recovery. Therefore, the exploration of FM as a safe and desired nanozyme provides a timely alternative to current antibiotic therapy against drug-resistant bacteria.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Pironas , Desinfecção , Compostos Férricos/farmacologia , Peroxidase do Rábano Silvestre , Catálise , Antibacterianos/farmacologia , Peróxido de Hidrogênio , Peroxidase
7.
Food Chem ; 444: 138678, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38330598

RESUMO

Conventional "all-in-one" methods for multi-component active packaging systems are not wholly adequate for fresh food. Given the need for multifunctional properties, introducing halloysite nanotubes (HNTs) could be a promising way to achieve controllable release of active ingredients while endowing with pH-sensitive performance. Here, we pioneered a GRAS composite with multifunctional properties, employing natural HNTs as a nanocarrier, citral (Cit) as an active antimicrobial agent, and myricetin (Myr) for monitoring freshness. The Cit-HNTs-Myr had excellent DPPH, ABTS and ·OH radical scavenging capacity, dual-model (contact and fumigant) antibacterial properties, and pH-sensitive performance. Subsequently, a smart tag prepared by dipping cellulose fibers into Cit-HNTs-Myr, which extended the shelf life of shrimp and blueberries, and provided freshness information for the shrimp. These results demonstrate the applicability of Cit-HNTs-Myr in the preservation of perishable goods and freshness monitoring.


Assuntos
Anti-Infecciosos , Nanotubos , Argila/química , Antibacterianos/farmacologia , Nanotubos/química , Conservação de Alimentos , Embalagem de Alimentos
8.
Toxicol Mech Methods ; : 1-12, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38390772

RESUMO

Irinotecan-induced severe diarrhea (IISD) not only limits irinotecan's application but also significantly affects patients' quality of life. However, existing animal models often inadequately represent the dynamics of IISD development, progression, and resolution across multiple chemotherapy cycles, yielding non-reproducible and highly variable response with limited clinical translation. Our studies aim to establish a reproducible and validated IISD model that better mimics the pathophysiology progression observed in patients, enhancing translational potential. We investigated the impact of dosing regimens (including different dose, infusion time, and two cycles of irinotecan administration), sex, age, tumor-bearing conditions, and irinotecan formulation on the IISD incidence and severity in mice and rats. Lastly, we investigated above factors' impact on pharmacokinetics of irinotecan, intestinal injury, and carboxylesterase activities. In summary, we successfully established a standard model establishment procedure for an optimized IISD model with highly reproducible severe diarrhea incidence rate (100%) and a low mortality rate (11%) in F344 rats. Additionally, the rats tolerated at least two cycles of irinotecan chemotherapy treatment. In contrast, the mouse model exhibited suboptimal IISD incidence rates (60%) and an extremely high mortality rate (100%). Notably, dosing regimen, age and tumor-bearing conditions of animals emerged as critical factors in IISD model establishment. In conclusion, our rat IISD model proves superior in mimicking pathophysiology progression and characteristics of IISD in patients, which stands as an effective tool for mechanism and efficacy studies in future chemotherapy-induced gut toxicity research.

9.
Food Funct ; 15(3): 1402-1416, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38214586

RESUMO

Fructooligosaccharides (FOS) and inulin are beneficial for human health. However, their benefits differ in individuals who consume prebiotics. Several factors contribute to this variation, including host genetics and differences in the gut microbiota. Bifidobacterium and Bacteroides are strong carbohydrate-utilizing bacteria in the gut, and the level of the Bacteroides/Bifidobacterium (Ba/Bi) ratio in the gut is closely related to the body's ability to utilize prebiotics. However, how to select the type of prebiotics more beneficial for populations with specific Ba/Bi backgrounds and the underlying regulatory mechanisms remain unclear. Here, we explored the dynamics of the gut microbiota and metabolic functions during the in vitro fermentation of FOS and inulin in two different groups: Bacteroides/Bifidobacterium high (H) and Bacteroides/Bifidobacterium low (L). This study revealed that the baseline Ba/Bi ratio had a greater impact on the gut microbiota compared to prebiotic species. Noticeable differences were observed between the two groups after prebiotic intervention, with the H group being more likely to benefit from the prebiotic intervention. Compared to the L group, the H group exhibited significantly higher microbial α-diversity; the co-abundance response group 1 (CARG1) members Ruminococcus gnavus and Blautia involved in the synthesis of propionic and butyric acids increased significantly, the abundance of pathogenic bacteria such as Escherichia Shigella decreased significantly, and the ability to degrade carbohydrates and synthesize fatty acids was greater. Regression modeling showed that the key microbiota could predict the short-chain fatty acid (SCFA) levels, with FOS associated with the ecological roles of CARG2 and CARG7 and inulin associated with CARG4, which provides the basis for the use of prebiotics in nutritional applications and the stratification of populations based on pertinent microbiota profiles to explain the incongruent health effects in human intervention studies.


Assuntos
Microbioma Gastrointestinal , Inulina , Humanos , Inulina/metabolismo , Fezes/microbiologia , Oligossacarídeos/metabolismo , Prebióticos , Bactérias/genética , Bactérias/metabolismo , Fermentação , Bifidobacterium/metabolismo
10.
Int J Mol Med ; 53(2)2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38063237

RESUMO

Iron overload and ferroptosis are associated with intervertebral disc degeneration (IDD); however, the mechanism underlying the regulation of iron homeostasis remains to be elucidated. Nuclear factor erythroid 2­related factor 2 (Nrf2) has been reported to regulate cellular iron homeostasis; however, its impact on IDD pathology and the underlying mechanism of action requires further investigation. In the present study, immunohistochemistry analysis of Nrf2 expression in the cartilage endplate (CEP) was conducted and it was demonstrated that Nrf2 expression was increased in the CEP at the early stages of the development of IDD, whereas it was decreased at the late stages of the development of IDD. The results of western blot analysis indicated that the inadequate activation of Nrf2 may aggravate mitochondrial dysfunction and oxidative stress, thus promoting CEP chondrocyte degeneration and calcification. It was also revealed that Nrf2 was involved in TNF­α­induced CEP chondrocyte iron metabolism dysfunction and ferroptosis. Inhibition of Nrf2 expression using Nrf2 small interfering RNA could enhance the process of nuclear receptor coactivator 4 (NCOA4)­mediated ferritinophagy and increase ferrous ion content, which may promote CEP chondrocyte ferroptotic cell death and extracellular matrix degradation. Furthermore, a decrease in cellular iron concentration may inhibit CEP chondrocyte ferroptosis, and CEP degeneration and calcification. The present study highlights the role of the Nrf2/NCOA4 axis in chondrocyte ferroptosis and IDD pathogenesis, thus suggesting that activation of Nrf2 may be a promising strategy for IDD treatment.


Assuntos
Calcinose , Degeneração do Disco Intervertebral , Fator 2 Relacionado a NF-E2 , Humanos , Calcinose/metabolismo , Cartilagem/metabolismo , Condrócitos/metabolismo , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/metabolismo , Ferro/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Coativadores de Receptor Nuclear/metabolismo
11.
BMC Gastroenterol ; 23(1): 430, 2023 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066428

RESUMO

BACKGROUND: There is no study evaluating the association between exercise and functional dyspepsia (FD) based on the Rome IV criteria. We aimed to investigate the prevalence of FD and evaluate the association between exercise and FD based on Rome IV criteria among a sample of Chinese armed police recruits. METHODS: An on-site questionnaire survey on FD among a sample of Chinese armed police recruits was conducted based on the Rome IV criteria in 2021. Potential confounders included age, body mass index (BMI), race, marriage, education, smoking, and drinking variables were adjusted. RESULTS: A total of 2594 recruits were enrolled, including 46 FD participants and 2548 non-FD participants. In the model adjusted for all demographic variables among participants excluding irritable bowel syndrome (IBS) and functional constipation (FC), compared with no exercise participants, 1 h < each exercise time ≤ 2 h (OR = 0.15, 95% CI: 0.03-0.77, P = 0.0230) was inversely associated with FD and compared with no exercise participants, mild exercise (OR = 0.09, 95% CI: 0.01-0.71, P = 0.0220) was significantly inversely associated with FD. CONCLUSIONS: The incidence rate of FD in this sample Chinese armed police recruits was 1.77%, and 1 h < each exercise time ≤ 2 h and mild intensity exercise were independently inversely associated with FD. However, the causal relationship needs to be verified by further randomized controlled trials.


Assuntos
Dispepsia , Síndrome do Intestino Irritável , Humanos , Masculino , Dispepsia/complicações , Polícia , Síndrome do Intestino Irritável/complicações , Constipação Intestinal/complicações , Inquéritos e Questionários , Prevalência , China/epidemiologia
12.
Genet Test Mol Biomarkers ; 27(12): 370-383, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38156909

RESUMO

Purpose: The aim of this study was to characterize key biomarkers associated with pyroptosis in atopic dermatitis (AD). Materials and methods: To identify the differentially expressed pyroptosis-related genes (DEPRGs), the gene expression profiles GSE16161 and GSE32924 from the Gene Expression Omnibus (GEO) database were utilized. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to determine the potential biological functions and involved pathways. Furthermore, protein-protein interaction network analyses were performed to identify hub genes. The types and proportions of infiltrating immune cells were detected by immune filtration analysis using CIBERSORT. A 12-axis competing endogenous RNA (ceRNA) network was constructed utilizing the miRNet database. Immunohistochemistry (IHC) further validated the differential expression of a key gene IRF1 in the skin tissues collected from AD patients. The collection of skin tissue from human subjects in this study were reviewed and approved by the IRB of Yueyang Integrated Chinese and Western Medicine Hospital (KYSKSB2020-125). Results: The study identified a total of 76 DEPRGs, which were enriched in genes associated with the inflammatory response and immune regulation. There was a higher percentage of activated dendritic cells and a lower percentage of resting mast cells in AD samples. PVT1 expression was associated with upregulation of hub genes including CXCL8, IRF1, MKI67, and TP53 in the ceRNA network and was correlated with activated dendritic cells in AD. As a transcription factor, IRF1 could regulate the production of downstream inflammatory factors. The IHC study revealed that IRF1 was overexpressed in the skin tissues of AD patients, which were consistent with the results of the bioinformatic study. Conclusions: IRF1 and its related genes were identified as key pyroptosis-related biomarkers in AD, which is a crucial pathway in the pathogenesis of AD.


Assuntos
Dermatite Atópica , Fator Regulador 1 de Interferon , Piroptose , Humanos , Biologia Computacional , Dermatite Atópica/genética , Fator Regulador 1 de Interferon/genética , Prognóstico , Piroptose/genética
13.
Anal Chem ; 95(46): 16958-16966, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37942854

RESUMO

Developing signal tracers (STAs) with large size, multifunctionality, and high retention bioaffinity is believed to be a potential solution for achieving high-performance immunochromatographic assays (ICAs). However, the size limitations of STAs on strips are always a challenge because of the serious steric hindrance. Here, based on metal-quinone coordination and further metal etching, hollow micron-tubular STAs formed by natural alizarin and Fe3+ ions (named ALIFe) are produced to break through size limitations, provide more active sites, and achieve three-mode ICAs (ALIFe STAs-ICAs). Thanks to the special tubular morphology, ALIFe can successfully pass through the strip and provide an ideal signal intensity within 7 min at low mAb and probe dosages to achieve stable ICA analysis. Importantly, ALIFe shows excellent antibody enrichment and bioaffinity retention capability. With a proof-of-concept for streptomycin, the ALIFe STAs-ICAs showed the limit of detection (LOD) at 0.39 ng mL-1 for colorimetric mode, 0.32 ng mL-1 for catalytic mode, and 0.016 ng mL-1 for photothermal mode with total recoveries ranging from 80.46 to 121.59% in mike and honey samples. We anticipate that our study will help expand the ideas for the design of high-performance STAs with large size and broaden the practical application of ICA.


Assuntos
Antibacterianos , Nanopartículas Metálicas , Cromatografia de Afinidade/métodos , Limite de Detecção , Nanopartículas Metálicas/química
14.
Food Chem Toxicol ; 182: 114171, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37956707

RESUMO

To identify additional genetic markers contributing to variability in CPT-11 disposition and toxicity, we assessed impact of the multiple drug-resistant transporters 1, 2, and 3 (MRP1, MRP2, and MRP3) on the intestinal toxicity, pharmacokinetics, tissue distribution and biliary excretion of CPT-11 using a knockout mouse model. Mrp1/3 knockout had minor impact on intestinal toxicity of CPT-11, tissue distribution, biliary excretion, and PK parameter of its active metabolites SN38. Conversely, Mrp2-/- mice, with low carboxylesterase activity, displayed insensitivity to CPT-11 toxicity due to reduced intestinal exposure to SN38. In PK studies, Mrp1/2 knockout significantly increased the AUC of CPT-11 compared to their AUC in FVB mice. However, the AUC of SN38 in Mrp2 -/- mice was decreased by 3.25-fold. Mrp3 knockout only slightly increased SN38 plasma exposure. Lastly, Mrp2/3 knockout increased biliary excretion amount of CPT-11 by 67.2% and 48.5% compared to wild-type mice, respectively. Consequently, Mrp1/3 deficiency didn't change SN38 tissue distribution. Finally, correlation analysis demonstrated that tissue exposure to SN38 was better correlated with toxicity than plasma AUC of SN38. Mrp1/2/3 deficiency showed a minor impact on PK, biliary excretion, distribution and intestinal exposure of SN38, and as a result, did not affect the intestinal toxicity of CPT-11.


Assuntos
Camptotecina , Intestinos , Camundongos , Animais , Irinotecano , Camptotecina/toxicidade , Distribuição Tecidual
15.
Food Res Int ; 174(Pt 1): 113598, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37986462

RESUMO

Prebiotics are known to modulate the gut microbiota, but there is host variability, mainly due to differences in carbohydrate-utilisation by gut microbiota. Bifidobacterium and Bacteroides are powerful carbohydrate-utilising bacteria, and the ratio of both is closely related to the utilisation of prebiotics. However, the differential impact of prebiotics on the composition and function of the gut microbiota and its metabolites in participants with different Bacteroides/Bifidobacterium (Ba/Bi) ratios have not been studied. Here, we conducted a 4-week randomised double-blind, parallel four-arm trial using two prebiotics (oligofructose and inulin) in two populations with high Ba/Bi (H) and low Ba/Bi (L). The response to prebiotics in both populations was influenced by the baseline microbiota background specificity. Notably, at an overall level, FOS was slightly better than inulin in modulating the gut microbiota. Difference in gut microbiota regulation by FOS across microbiota contexts were significant between the two groups. Butyric acid-producing bacteria were significantly more abundant in H and further elevated butyric acid and related metabolite levels, with H more likely to benefit from the FOS intervention. The two groups showed only metabolic differences in their response to inulin, with L showing a significant increase in propionic acid and being enriched in glycolysis functions, whereas H was enriched in amino acids and aminoglycolysis functions. Overall, these results provide a basis for selecting appropriate prebiotics for participants with different gut backgrounds.


Assuntos
Microbioma Gastrointestinal , Inulina , Humanos , Bacteroides , Bifidobacterium/metabolismo , Fezes/microbiologia , Bactérias/metabolismo , Ácido Butírico/análise , Ácido Butírico/metabolismo
16.
Elife ; 122023 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-37982489

RESUMO

The MRTF-SRF pathway has been extensively studied for its crucial role in driving the expression of a large number of genes involved in actin cytoskeleton of various cell types. However, the specific contribution of MRTF-SRF in hair cells remains unknown. In this study, we showed that hair cell-specific deletion of Srf or Mrtfb, but not Mrtfa, leads to similar defects in the development of stereocilia dimensions and the maintenance of cuticular plate integrity. We used fluorescence-activated cell sorting-based hair cell RNA-Seq analysis to investigate the mechanistic underpinnings of the changes observed in Srf and Mrtfb mutants, respectively. Interestingly, the transcriptome analysis revealed distinct profiles of genes regulated by Srf and Mrtfb, suggesting different transcriptional regulation mechanisms of actin cytoskeleton activities mediated by Srf and Mrtfb. Exogenous delivery of calponin 2 using Adeno-associated virus transduction in Srf mutants partially rescued the impairments of stereocilia dimensions and the F-actin intensity of cuticular plate, suggesting the involvement of Cnn2, as an Srf downstream target, in regulating the hair bundle morphology and cuticular plate actin cytoskeleton organization. Our study uncovers, for the first time, the unexpected differential transcriptional regulation of actin cytoskeleton mediated by Srf and Mrtfb in hair cells, and also demonstrates the critical role of SRF-CNN2 in modulating actin dynamics of the stereocilia and cuticular plate, providing new insights into the molecular mechanism underlying hair cell development and maintenance.


Assuntos
Citoesqueleto de Actina , Células Ciliadas Auditivas , Células Ciliadas Auditivas/fisiologia , Citoesqueleto de Actina/metabolismo , Estereocílios/metabolismo , Actinas/genética , Actinas/metabolismo , Regulação da Expressão Gênica
17.
Adv Sci (Weinh) ; 10(33): e2303078, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37870181

RESUMO

Strong substrate affinity and high catalytic efficiency are persistently pursued to generate high-performance nanozymes. Herein, with unique surface atomic configurations and distinct d-orbital coupling features of different metal components, a class of highly efficient MnFeCoNiCu transition metal high-entropy nanozymes (HEzymes) is prepared for the first time. Density functional theory calculations demonstrate that improved d-orbital coupling between different metals increases the electron density near the Fermi energy level (EF ) and shifts the position of the overall d-band center with respect to EF , thereby boosting the efficiency of site-to-site electron transfer while also enhancing the adsorption of oxygen intermediates during catalysis. As such, the proposed HEzymes exhibit superior substrate affinities and catalytic efficiencies comparable to that of natural horseradish peroxidase (HRP). Finally, HEzymes with superb peroxidase (POD)-like activity are used in biosensing and antibacterial applications. These results suggest that HEzymes have great potential as new-generation nanozymes.


Assuntos
Peroxidase , Elementos de Transição , Entropia , Peroxidases , Catálise , Corantes
18.
Ecotoxicol Environ Saf ; 266: 115605, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37864966

RESUMO

2-Ethylhexyl diphenyl phosphate (EHDPP) is one of the typical organophosphate flame retardants (OPFRs) and has been widely detected in environmental media. Exposure to EHDPP during pregnancy affects placental development and fetal growth. Liver X receptor α (LXRα) is essential to placental development. However, finite information is available regarding the function of LXRα in placenta damages caused by EHDPP. In present study we investigated to figure out whether LXRα is playing roles in EHDPP-induced placenta toxicity. While EHDPP restrained cell viability, migration, and angiogenesis dose-dependently in HTR-8/SVneo and JEG-3 cells, overexpression or activation by agonist T0901317 of LXRα alleviated the above phenomenon, knockdown or inhibition by antagonist GSK2033 had the opposite effects in vitro. Further study indicated EHDPP decreased LXRα expression and transcriptional activity leading to mRNA, protein expression levels downregulation of viability, migration, angiogenesis-related genes Forkhead box M1 (Foxm1), endothelial nitric oxide synthase (eNos), matrix metalloproteinase-2 (Mmp-2), matrix metalloproteinase-9 (Mmp-9), vascular endothelial growth factor-A (Vegf-a) and upregulation of inflammatory genes interleukin-6 (Il-6), interleukin-1ß (Il-1ß) and tumor necrosis factor-α (Tnf-α) in vitro and in vivo. Moreover, EHDPP caused decreased placental volume and fetal weight in mice, treatment with LXRα agonist T0901317 restored these adverse effects. Taken together, our study unveiled EHDPP-induced placenta toxicity and the protective role of LXRα in combating EHDPP-induced placental dysfunction. Activating LXRα could serve as a therapeutic strategy to reverse EHDPP-induced placental toxicity.


Assuntos
Metaloproteinase 2 da Matriz , Fosfatos , Feminino , Gravidez , Animais , Camundongos , Receptores X do Fígado/genética , Fator A de Crescimento do Endotélio Vascular , Linhagem Celular Tumoral , Placenta
19.
Expert Rev Vaccines ; 22(1): 900-905, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37843409

RESUMO

BACKGROUND: While studies have demonstrated that certain COVID-19 vaccines administered during pregnancy did not affect neonatal or maternal outcomes significantly, the safety of inactivated SARS-CoV-2 vaccines in China, given during the first trimester, remains to be fully elucidated. METHOD: A retrospective cohort study was conducted involving female participants who gave birth from January to October 2021. The study compared pregnancy, delivery, and neonatal outcomes between subjects who received one or two doses of the inactivated COVID-19 vaccines during their first trimester and unvaccinated control subjects. RESULTS: A total of 2658 pregnant women was recruited. Among them, 2358 (88.7%) reported ongoing pregnancies; 326 (13.8%) of these were vaccinated. Additionally, 277 (10.4%) experienced spontaneous miscarriages between 6 to 20 gestational weeks; 40 (14.4%) of these were vaccinated, yielding an odds ratio of 0.67-1.36 (95% confidence interval) for COVID-19 vaccination. The comparison of neonatal complications, including an Apgar score less than 7, preterm birth, low birth weight, and newborn respiratory complications, between unvaccinated and vaccinated participants revealed no statistical significance. CONCLUSION: The administration of COVID-19 inactivated vaccines during the first trimester of pregnancy is not associated with adverse pregnancy or neonatal outcomes, providing a substantial ground for pertinent health education.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Feminino , Humanos , Recém-Nascido , Gravidez , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/administração & dosagem , Resultado da Gravidez , Primeiro Trimestre da Gravidez , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos , SARS-CoV-2 , Vacinas de Produtos Inativados/efeitos adversos
20.
Nano Lett ; 23(20): 9563-9570, 2023 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-37819937

RESUMO

Traditional disposable personal protective equipment (PPE) only blocks pathogenic bacteria by mechanical filtration, with the risk of recontamination and transmission remaining. Herein, inspired by phenolic-enabled nanotechnology (PEN), we proposed engineered polyphenol coatings by plant-derived aromatic aldehydes and metal involvement, denoted as FQM, to obtain the desired photocatalysis-self-Fenton antibacterial performance. Experiments and theoretical analysis proved the dual mechanism of Fe-induced enhancement: (1) tuning of molecular structure realized improved optical properties; (2) Fe(III)/Fe(II) triggered photocatalytic cascade self-Fenton reaction. Mechanism study reveals FQM killing bacteria by direct-contact ROS attack and gene regulation. Further, the FQM was developed as the ideal antibacterial coating on different fabrics (cloth cotton, polyester, and N95 mask), killing more than 93% of bacteria after 5 cycles of use. Such photocatalysis-self-Fenton coatings based on engineered polyphenols endowed with desirable safety, sustainability, and efficient antibacterial features are promising solutions to meet the challenges of the currently available PPE.


Assuntos
Compostos Férricos , Polifenóis , Polifenóis/farmacologia , Polifenóis/química , Têxteis , Antibacterianos/farmacologia , Antibacterianos/química
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