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1.
Cell Death Dis ; 15(10): 725, 2024 Oct 02.
Article de Anglais | MEDLINE | ID: mdl-39358349

RÉSUMÉ

Pancreatic cancer is one of the leading causes of cancer-associated mortality, with a poor treatment approach. Previous study has shown that inducing pyroptosis in pancreatic ductal adenocarcinoma (PDAC) slows the growth of PDACs, implying that pyroptosis inducers are potentially effective for PDAC therapy. Here, we found that Dronedarone hydrochloride (DH), an antiarrhythmic drug, induces pyroptosis in pancreatic cancer cells and inhibits PDAC development in mice. In PANC-1 cells, DH caused cell death in a dosage- and time-dependent manner, with only pyroptosis inhibitors and GSDMD silencing rescuing the cell death, indicating that DH triggered GSDMD-dependent pyroptosis. Further work revealed that DH increased mitochondrial stresses and caused mitochondrial DNA (mtDNA) leakage, activating the cytosolic STING-cGAS and pyroptosis pathways. Finally, we assessed the anti-cancer effects of DH in a pancreatic cancer mouse model and found that DH treatment suppressed pancreatic tumor development in vivo. Collectively, our investigation demonstrates that DH triggers pyroptosis in PDAC and proposes its potential effects on anti-PDAC growth.


Sujet(s)
ADN mitochondrial , Dronédarone , Tumeurs du pancréas , Pyroptose , Pyroptose/effets des médicaments et des substances chimiques , Animaux , Tumeurs du pancréas/traitement médicamenteux , Tumeurs du pancréas/anatomopathologie , Tumeurs du pancréas/métabolisme , Tumeurs du pancréas/génétique , Humains , Dronédarone/pharmacologie , ADN mitochondrial/métabolisme , ADN mitochondrial/génétique , Souris , Lignée cellulaire tumorale , Carcinome du canal pancréatique/traitement médicamenteux , Carcinome du canal pancréatique/anatomopathologie , Carcinome du canal pancréatique/métabolisme , Carcinome du canal pancréatique/génétique , Souris nude
2.
J Cardiovasc Pharmacol ; 84(3): 347-355, 2024 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-39240730

RÉSUMÉ

ABSTRACT: Guidelines on antiplatelet recommendation for CYP2C19 intermediate metabolizer (IM) have not come to an agreement. This study aimed to evaluate the clinical benefit of ticagrelor when compared with high-dose clopidogrel in CYP2C19 IM after percutaneous coronary intervention for acute coronary syndromes. Patients were enrolled according to CYP2C19 genotype and individual antiplatelet therapy. Patient characteristics and clinical outcomes were collected through electronic medical record system. The primary outcome was major adverse cardiac and cerebrovascular event (MACCE), namely a composite of death from cardiovascular causes, myocardial infarction, stroke, and stent thrombosis within 12 months. The secondary outcome was Bleeding Academic Research Consortium scale bleeding events within 12 months. The Cox proportional hazards regression model was performed, with inverse probability treatment weighting (IPTW) adjusting for potential confounders. A total of 532 CYP2C19 IM were enrolled in this retrospective single-center study. No statistically significant difference in incidence rate of MACCE was found between patients receiving ticagrelor versus clopidogrel (7.01 vs. 9.52 per 100 patient-years; IPTW-adjusted hazard ratio 0.71; 95% confidence interval: 0.32-1.58; adjusted log-rank P = 0.396), but the incidence rate of Bleeding Academic Research Consortium type 2, 3, or 5 bleeding events was statistically higher in the loss of function-ticagrelor group than in the loss of function-clopidogrel group (13.53 vs. 6.16 per 100 patient-years; IPTW-adjusted hazard ratio: 2.29; 95% confidence interval: 1.10-4.78; adjusted log-rank P = 0.027). Ticagrelor treatment in CYP2C19 IM resulted in a statistically higher risk of bleeding compared with high-dose clopidogrel, whereas a clear association between treatments and MACCE warrants further investigations.


Sujet(s)
Syndrome coronarien aigu , Clopidogrel , Cytochrome P-450 CYP2C19 , Hémorragie , Intervention coronarienne percutanée , Variants pharmacogénomiques , Antiagrégants plaquettaires , Ticagrélor , Humains , Cytochrome P-450 CYP2C19/génétique , Cytochrome P-450 CYP2C19/métabolisme , Ticagrélor/effets indésirables , Ticagrélor/administration et posologie , Clopidogrel/effets indésirables , Clopidogrel/administration et posologie , Syndrome coronarien aigu/thérapie , Syndrome coronarien aigu/mortalité , Syndrome coronarien aigu/diagnostic , Mâle , Intervention coronarienne percutanée/effets indésirables , Intervention coronarienne percutanée/mortalité , Femelle , Antiagrégants plaquettaires/effets indésirables , Antiagrégants plaquettaires/administration et posologie , Adulte d'âge moyen , Sujet âgé , Études rétrospectives , Résultat thérapeutique , Hémorragie/induit chimiquement , Facteurs de risque , Facteurs temps , Appréciation des risques , Phénotype
3.
J Youth Adolesc ; 2024 Sep 09.
Article de Anglais | MEDLINE | ID: mdl-39251471

RÉSUMÉ

The adversity faced by left-behind children due to parental migration affects their depressive symptoms, but little is known about the mechanism underlying this association and protective factors from a dynamic perspective. The present study examined the association between family adversity and the developmental trajectory of depressive symptoms, and the potential mediating and moderating role of personal growth initiative in this association among left-behind children. A total of 363 left-behind children (48.8% female; Mage = 12.97 at T1, SDage = 0.55) from five rural middle schools in the Hunan Province of China participated in this three-wave study, employing one-year intervals between assessments. The results indicated the initial level of personal growth initiative mediated the association between family adversity at T1 and the development of depressive symptoms, while the growth rate of personal growth initiative both mediated and moderated this association, with consistent effects across sexes. These findings underscore the critical role of personal growth initiative in the association between family adversity and depressive symptoms among left-behind children.

4.
Cell Signal ; 124: 111378, 2024 Sep 04.
Article de Anglais | MEDLINE | ID: mdl-39241901

RÉSUMÉ

Crosstalk between cancer-associated fibroblasts (CAFs) and tumour cells plays a critical role in multiple cancers, including hepatocellular carcinoma (HCC). CAFs contribute to tumorigenesis by secreting growth factors, modifying the extracellular matrix, supporting angiogenesis, and suppressing antitumor immune responses. However, effect and mechanism of CAF-mediated promotion of hepatocellular carcinoma cells are still unclear. In study, we demonstrated CAFs promoted the proliferation and inhibited the apoptosis of HCC cells by secreting interleukin-6 (IL-6), which induced autocrine insulin-like growth factor-1 (IGF-1) in HCC. IGF-1 promoted the progression and chemoresistance of HCC. IGF-1 receptor (IGF-1R) inhibitor NT157 abrogated the effect of CAF-derived IL-6 and autocrine IGF-1 on HCC. Mechanistic studies revealed that NT157 decreased IL-6-induced IGF-1 expression by inhibiting STAT3 phosphorylation and led to IRS-1 degradation, which mediated the proliferation of tumour by activating AKT signalling in ERK-dependent manner. Inhibition of IGF-1R also enhanced the therapeutic effect of sorafenib on HCC, especially chemoresistant tumours. STATEMENT OF SIGNIFICANCE: Our study showed IL-6-IGF-1 axis played crucial roles in the crosstalk between HCC and CAFs, providing NT157 inhibited of STAT3 and IGF-1R as a new targeted therapy in combination with sorafenib.

5.
Pancreatology ; 2024 Sep 14.
Article de Anglais | MEDLINE | ID: mdl-39327124

RÉSUMÉ

OBJECTIVES: To evaluate the efficacy of quantitative parameters from dual-energy CT (DECT) and basic CT features in predicting the postoperative early recurrence (ER) of pancreatic ductal adenocarcinoma (PDAC). METHODS: In this study, patients with PDAC who underwent radical resection and DECT from 2018 to 2022 were enrolled and categorised into ER and non-ER groups. The clinical data, basic CT features and DECT parameters of all patients were analyzed. Independent predictors of ER were identified with Logistic regression analyses. Three models (model A: basic CT features; model B: DECT parameters; model C: basic CT features + DECT parameters) were established. Receiver operating characteristic curve analysis was utilized to evaluate predictive performance. RESULTS: A total of 150 patients were enrolled (ER group: n = 63; non-ER group: n = 87). Rim enhancement (odds ratio [OR], 3.32), peripancreatic strands appearance (OR, 2.68), electron density in the pancreatic parenchymal phase (P-Rho; OR, 0.90), arterial enhancement fraction (AEF; OR, 0.05) and pancreatic parenchyma fat fraction in the delayed phase (OR, 1.25) were identified as independent predictors of ER. Model C showed the highest area under the curve of 0.898. In addition, the corresponding ER risk factors were identified separately for resectable and borderline resectable PDAC subgroups. CONCLUSIONS: DECT quantitative parameters allow for the noninvasive prediction of postoperative ER in patients with PDAC, and the combination of DECT parameters and basic CT features shows a high prediction efficiency. Our model can help to identify patients with high-risk factors to guide preoperative decision making.

6.
J Am Chem Soc ; 146(39): 27022-27029, 2024 Oct 02.
Article de Anglais | MEDLINE | ID: mdl-39292646

RÉSUMÉ

Chemical synapse completes the signaling through neurotransmitter-mediated ion flux, the emulation of which has been a long-standing obstacle in neuromorphic exploration. Here, we report metal-organic framework (MOF) nanofluidic synapses in which conjugated MOFs with abundant ionic storage sites underlie the ionic hysteresis and simultaneously serve as catalase mimetics that sensitively respond to neurotransmitter glutamate (Glu). Various neurosynaptic patterns with adaptable weights are realized via Glu-mediated chemical/ionic coupling. In particular, nonlinear Hebbian and anti-Hebbian learning in millisecond time ranges are achieved, akin to those of chemical synapses. Reversible biochemical in-memory encoding via enzymatic Glu clearance is also accomplished. Such results are prerequisites for highly bionic electrolytic computers.


Sujet(s)
Acide glutamique , Réseaux organométalliques , Synapses , Réseaux organométalliques/composition chimique , Acide glutamique/composition chimique , Synapses/composition chimique , Synapses/métabolisme , Nanotechnologie/méthodes , Catalase/composition chimique , Catalase/métabolisme
7.
BMC Neurol ; 24(1): 313, 2024 Sep 04.
Article de Anglais | MEDLINE | ID: mdl-39232681

RÉSUMÉ

BACKGROUND: There is still a lack of knowledge about the relationship between metabolic syndrome (MetS) and Parkinson's disease (PD). This study aimed to determine whether MetS increases PD risk. METHODS: To identify relevant clinical studies, databases such as PubMed, Embase, and the Cochrane Library were searched in depth from the inception of databases until March 31, 2024. The study evaluated the correlation between MetS and the likelihood of developing PD through the computation of aggregated relative risks (RR) and their respective 95% confidence intervals (CIs) utilizing selnRR and lnRR. RESULTS: Seven studies were included in our systematic review. The meta-analysis revealed that patients with MetS have a 0.3-fold increased risk of developing PD (p = 0.001). Furthermore, the analysis revealed a positive correlation between central obesity and the incidence of PD, with an RR of 1.19 (95% CI, 1.16-1.22; p = 0.001), as well as a greater risk of PD in patients with elevated blood pressure, with an RR of 1.13 (95% CI, 1.07-1.19; p = 0.001); elevated serum triglyceride levels, with an RR of 1.09 (95% CI, 1.02-1.15; p = 0.001); lower serum HDL cholesterol levels, with an RR of 1.21 (95% CI, 1.15-1.28; p = 0.001); and elevated plasma fasting glucose levels, with an RR of 1.18 (95% CI, 1.11-1.26; p = 0.001). CONCLUSION: MetS can contribute to the incidence of Parkinson's disease, with individual components of MetS demonstrating comparable effects.


Sujet(s)
Syndrome métabolique X , Maladie de Parkinson , Maladie de Parkinson/épidémiologie , Maladie de Parkinson/sang , Humains , Syndrome métabolique X/épidémiologie , Facteurs de risque
8.
Water Res ; 267: 122453, 2024 Sep 16.
Article de Anglais | MEDLINE | ID: mdl-39306934

RÉSUMÉ

H2O2 as a green oxidant plays a crucial role in numerous green chemical reactions. However, how to improve its activation and utilization efficiency as well as regulate the distribution of ROS remains a pressing challenge. In this work, a sulfur quantum dots (SQDs) modified zero-valent iron (SQDs@ZVI) was delicately designed and prepared, whose iron sites can coordinate with strongly electronegative sulfur atoms to construct highly reactive Fe-S dual active sites, for high-efficient selective H2O2 activation and utilization with potent •OH production. Experimental tests, in situ FTIR/Raman spectra and theoretical calculations demonstrated that SQDs modulates the local coordination structure and electronic density of iron centers, thus effectively enhancing its Fenton reactivity and promoting the rate-limiting H2O2 adsorption and subsequent barrierless dissociation of peroxyl bonds into •OH via the formation of bridged S-O-O-Fe complexes. Consequently, substantial generated surface-bound •OH induced by the highly reactive Fe-S dual sites enabled excellent degradation of miscellaneous organic pollutants over a broad pH range (3.0-9.0). The developed device-scale Fenton filter realized durable performance (up to 200 h), verifying the vast potential of SQDs@ZVI with diatomic sites for practical application. This work presents a promising strategy to construct metal-nonmetal diatomic active sites toward boosting selective activation and effective utilization of H2O2, which may inspire the design of efficient heterogeneous Fenton reaction for water decontamination.

9.
Antiviral Res ; 231: 106007, 2024 Sep 17.
Article de Anglais | MEDLINE | ID: mdl-39299548

RÉSUMÉ

Respiratory syncytial virus (RSV) is a significant cause of acute lower respiratory tract infections, particularly in vulnerable populations such as neonates, infants, young children, and the elderly. Among infants, RSV is the primary cause of bronchiolitis and pneumonia, contributing to a notable proportion of child mortality under the age of 5. In this study, we focused on investigating the pathogenicity of a lethal RSV strain, GZ08-18, as a model for understanding mechanisms of hypervirulent RSV. Our findings indicate that the heightened pathogenicity of GZ08-18 stems from compromised activation of intrinsic apoptosis, as evidenced by aberration of mitochondrial membrane depolarization in host cells. We thus hypothesized that enhancing intrinsic apoptosis could potentially attenuate the virulence of RSV strains and explored the effects of Rotenone, a natural compound known to stimulate the intrinsic apoptosis pathway, on inhibiting RSV infection. Our results demonstrate that Rotenone treatment significantly improved mouse survival rates and mitigated lung pathology following GZ08-18 infection. These findings suggest that modulating the suppressed apoptosis induced by RSV infection represents a promising avenue for antiviral intervention strategies.

10.
Sci Rep ; 14(1): 19903, 2024 08 27.
Article de Anglais | MEDLINE | ID: mdl-39191828

RÉSUMÉ

Yaks live in the Qinghai-Tibet Plateau for a long time where oxygen is scarce, but can ensure the smooth development of testis and spermatogenesis. The key lies in the functional regulation of the Sertoli cells under hypoxia. In this study, we sequenced yak Sertoli cells cultured in normal oxygen concentration (Normoxia) and treated with low oxygen concentration (Hypoxia) by whole transcriptomics, and screened out 194 differentially expressed mRNAs (DEmRNAs), 934 differentially expressed LncRNAs (DELncRNAs) and 129 differentially expressed miRNAs (DEmiRNAs). GO and KEGG analysis showed that these differential genes were mainly concentrated in PI3K-AKT, MAPK, RAS, and other signaling pathways, and were associated with glucose metabolism, tight junction, steroid hormone synthesis, cell fusion, and immunity of yak Sertoli cells. We constructed the gene interaction network of yak Sertoli cells in hypoxia and screened out the relationship pairs related to glucose metabolism and tight junction. The results suggested that the changes in energy metabolism, tight junction, and immune regulation of yak Sertoli cells under hypoxia might provide favorable conditions for spermatogenesis. This study provides data for further study on the role of non-coding RNA in testis development and spermatogenesis of yak.


Sujet(s)
Hypoxie cellulaire , Réseaux de régulation génique , Cellules de Sertoli , Cellules de Sertoli/métabolisme , Animaux , Mâle , Bovins , Hypoxie cellulaire/génétique , Transcriptome , Analyse de profil d'expression de gènes , ARN long non codant/génétique , microARN/génétique , microARN/métabolisme , Spermatogenèse/génétique , ARN messager/génétique , ARN messager/métabolisme , Transduction du signal , Cellules cultivées , Régulation de l'expression des gènes
11.
ACS Appl Mater Interfaces ; 16(36): 48342-48351, 2024 Sep 11.
Article de Anglais | MEDLINE | ID: mdl-39216006

RÉSUMÉ

A series of slide-ring polyrotaxanes (SRPs) have been constructed by the solvent-free blending of a ditopic pillar[5]arene (DP5A) and polyisoprene (PIP) after thermal annealing. Solid-state 13C NMR experiments supported the fact that the pillar[5]arene rings of DP5A were threaded by PIP chains to afford physically interlocked networks. Tensile tests revealed that 1% of DP5A can improve the elongation at break from 50 to 239%, the tensile modulus from 2.1 to 3.9 MPa, and the toughness from 0.35 to 4.5 MJ/m3. Impact and puncture resistance experiments show that the DP5A-doped materials exhibit remarkable enhancement of protective and impalement-resistant performance. The samples can be also recycled repeatedly due to their physical crosslinking nature. The important stress delocalization effects have been attributed to the pulley effect of DP5A in the SRP materials, which represents a supramolecular approach for improving the performance of PIP elastomers.

12.
Zhongguo Zhong Yao Za Zhi ; 49(14): 3894-3900, 2024 Jul.
Article de Chinois | MEDLINE | ID: mdl-39099363

RÉSUMÉ

This study explored the effect of Tianma Gouteng Decoction on oxidative stress induced by angiotensin Ⅱ(AngⅡ) in vascular smooth muscle cell(VSMC) and its molecular mechanism. Primary rat VSMC were cultured using tissue block method, and VSMC were identified by α-actin immunofluorescence staining. AngⅡ at a concentration of 1×10~(-6) mol·L~(-1) was used as the stimulating factor, and Sprague Dawley(SD) rats were orally administered with Tianma Gouteng Decoction to prepare drug serum. Rat VSMC were divided into normal group, model group, Chinese medicine group, and inhibitor(3-methyladenine, 3-MA) group. Cell counting kit-8(CCK-8) assay was used to detect cell proliferation activity. Bromodeoxyuridine(BrdU) flow cytometry was used to detect cell cycle. Transwell assay was used to detect cell migration ability. Enzyme-linked immunosorbent assay(ELISA) was used to detect the activity of superoxide dismutase(SOD), catalase(CAT), and malondialdehyde(MDA) in VSMC. The intracellular reactive oxygen species(ROS) fluorescence intensity was detected using DCFH-DA fluorescent probe. Western blot was used to detect the expression of PTEN-induced putative kinase 1(PINK1), Parkin, p62, and microtubule-associated protein 1A/1B-light chain 3(LC3-Ⅱ) proteins in VSMC. The results showed that Tianma Gouteng Decoction-containing serum at a concentration of 8% could significantly inhibit VSMC growth after 48 hours of intervention. Compared with the normal group, the model group showed significantly increased cell proliferation activity and migration, significantly decreased levels of SOD and CAT, significantly increased levels of MDA, significantly enhanced ROS fluorescence intensity, significantly decreased expression of PINK1, Parkin, and LC3-Ⅱ proteins, and significantly increased expression of p62 protein. Compared with the model group, the Chinese medicine group showed significantly reduced cell proliferation activity and migration, significantly increased levels of SOD and CAT, significantly decreased levels of MDA, significantly weakened ROS fluorescence intensity, significantly increased expression of PINK1, Parkin, and LC3-Ⅱ proteins, and significantly decreased expression of p62 protein. Compared with the Chinese medicine group, the addition of the mitochondrial autophagy inhibitor 3-MA could block the intervention of Tianma Gouteng Decoction-containing serum on VSMC proliferation, migration, mitochondrial autophagy, and oxidative stress levels, with statistically significant differences. In summary, Tianma Gouteng Decoction has good antioxidant activity and can inhibit cell proliferation and migration. Its mechanism of action may be related to the activation of the mitochondrial autophagy PINK1/Parkin signaling pathway.


Sujet(s)
Angiotensine-II , Prolifération cellulaire , Médicaments issus de plantes chinoises , Muscles lisses vasculaires , Stress oxydatif , Protein kinases , Rat Sprague-Dawley , Ubiquitin-protein ligases , Animaux , Médicaments issus de plantes chinoises/pharmacologie , Stress oxydatif/effets des médicaments et des substances chimiques , Rats , Muscles lisses vasculaires/effets des médicaments et des substances chimiques , Muscles lisses vasculaires/cytologie , Muscles lisses vasculaires/métabolisme , Mâle , Prolifération cellulaire/effets des médicaments et des substances chimiques , Ubiquitin-protein ligases/métabolisme , Ubiquitin-protein ligases/génétique , Protein kinases/métabolisme , Protein kinases/génétique , Myocytes du muscle lisse/effets des médicaments et des substances chimiques , Myocytes du muscle lisse/métabolisme , Espèces réactives de l'oxygène/métabolisme , Mouvement cellulaire/effets des médicaments et des substances chimiques , Transduction du signal/effets des médicaments et des substances chimiques , Cellules cultivées , Superoxide dismutase/métabolisme
13.
J Vis Exp ; (209)2024 Jul 26.
Article de Anglais | MEDLINE | ID: mdl-39141532

RÉSUMÉ

Due to the limited accessibility of the human retina, retinal organoids (ROs) are the best model for studying human retinal disease, which could reveal the mechanism of retinal development and the occurrence of retinal disease. Microglia (MG) are unique resident macrophages in the retina and central nervous system (CNS), serving crucial immunity functions. However, retinal organoids lack microglia since their differentiation origin is the yolk sac. The specific pathogenesis of microglia in these retinal diseases remains unclear; therefore, the establishment of a microglia-incorporated retinal organoid model turns out to be necessary. Here, we successfully constructed a co-cultured model of retinal organoids with microglia derived from human stem cells. In this article, we differentiated microglia and then co-cultured to retinal organoids in the early stage. As the incorporation of immune cells, this model provides an optimized platform for retinal disease modeling and drug screening to facilitate in-depth research on the pathogenesis and treatment of retinal and CNS-related diseases.


Sujet(s)
Techniques de coculture , Microglie , Organoïdes , Rétine , Organoïdes/cytologie , Microglie/cytologie , Rétine/cytologie , Humains , Techniques de coculture/méthodes , Différenciation cellulaire/physiologie
14.
STAR Protoc ; 5(3): 103028, 2024 Sep 20.
Article de Anglais | MEDLINE | ID: mdl-39088323

RÉSUMÉ

COVID-19 casualties vary among different ancestral groups due to a variety of factors. Here, we present a protocol for analyzing publicly available genome-wide association studies (GWASs) to search for ancestry-specific genetic factors related to severe COVID-19. We describe steps for downloading and comparing two COVID-19 GWASs, calculating expression quantitative trait loci, and single-cell gene expression analysis. We demonstrate this approach using GWASs from Host Genetics Initiative; however, it is applicable to other databases such as the UK Biobank. For complete details on the use and execution of this protocol, please refer to Cheng et al.1.


Sujet(s)
COVID-19 , Étude d'association pangénomique , Locus de caractère quantitatif , SARS-CoV-2 , Étude d'association pangénomique/méthodes , Humains , COVID-19/génétique , COVID-19/virologie , SARS-CoV-2/génétique , Locus de caractère quantitatif/génétique , Prédisposition génétique à une maladie/génétique , Polymorphisme de nucléotide simple/génétique
15.
Res Pract Thromb Haemost ; 8(4): 102443, 2024 May.
Article de Anglais | MEDLINE | ID: mdl-38993621

RÉSUMÉ

Background: Salvianolic acid B (SAB) is a major component of Salvia miltiorrhiza root (Danshen), widely used in East/Southeast Asia for centuries to treat cardiovascular diseases. Danshen depside salt, 85% of which is made up of SAB, is approved in China to treat chronic angina. Although clinical observations suggest that Danshen extracts inhibited arterial and venous thrombosis, the exact mechanism has not been adequately elucidated. Objective: To delineate the antithrombotic mechanisms of SAB. Methods: We applied platelet aggregation and coagulation assays, perfusion chambers, and intravital microscopy models. The inhibition kinetics and binding affinity of SAB to thrombin are measured by thrombin enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. We used molecular in silico docking models to predict the interactions of SAB with thrombin. Results: SAB dose-dependently inhibited platelet activation and aggregation induced by thrombin. SAB also reduced platelet aggregation induced by adenosine diphosphate and collagen. SAB attenuated blood coagulation by modifying fibrin network structures and significantly decreased thrombus formation in mouse cremaster arterioles and perfusion chambers. The direct SAB-thrombin interaction was confirmed by enzymatic assays, intrinsic fluorescence spectrophotometry, and isothermal titration calorimetry. Interestingly, SAB shares key structural similarities with the trisubstituted benzimidazole class of thrombin inhibitors, such as dabigatran. Molecular docking models predicted the binding of SAB to the thrombin active site. Conclusion: Our data established SAB as the first herb-derived direct thrombin catalytic site inhibitor, suppressing thrombosis through both thrombin-dependent and thrombin-independent pathways. Purified SAB may be a cost-effective agent for treating arterial and deep vein thrombosis.

16.
BMC Public Health ; 24(1): 1760, 2024 Jul 02.
Article de Anglais | MEDLINE | ID: mdl-38956571

RÉSUMÉ

OBJECTIVE: Adverse childhood experiences (ACEs) have been associated with a range of adverse health outcomes, with pain being potentially one of them. This population-based cross-sectional study aimed to investigate the associations between Adverse Childhood Experiences (ACEs) and pain in Chinese adults and evaluate whether physical activity and demographic and socioeconomic characteristics modify this associations. METHODS: Cross-sectional data from the China Health and Retirement Longitudinal Study (CHARLS), were utilized in this study. A total of 9923 respondents with information on 12 ACE indicators and 15 self-reported body pains were included. Logistic regression models were used to assess associations of the ACEs and pain. Modification of the associations by physical activity, demographic and socioeconomic characteristics was assessed by stratified analyses and tests for interaction. RESULTS: Among the 9923 individuals included in the primary analyses, 5098 (51.4%) males and the mean (SD) age was 61.18 (10·.44) years. Compared with individuals with 0 ACEs, those who with ≥ 5 ACEs had increased risk of single pains and multiple pain. A dose-response association was found between the number of ACEs and the risk of pain (e.g. neck pain for ≥ 5 ACEs vs. none: OR, 1.107; 95% CI, 0.903-1.356; p < 0.001 for trend). In the associations of each body pain with each ACE indicator, most ACE indicators were associated with an increased risk of pain. In addition, physical activity, sociodemographic and socioeconomic characteristics, such as age, sex, educational level, area of residence, childhood economic hardship, did not demonstrate a significant modify on the associations between ACEs and pain. CONCLUSIONS: These findings indicate that cumulative ACE exposure is associated with increased odds of self-reported pain in Chinese adults, regardless of adult physical activity, sociodemographic and socioeconomic characteristics.


Sujet(s)
Expériences défavorables de l'enfance , Douleur , Humains , Mâle , Femelle , Chine/épidémiologie , Études longitudinales , Expériences défavorables de l'enfance/statistiques et données numériques , Adulte d'âge moyen , Études transversales , Sujet âgé , Douleur/épidémiologie , Exercice physique , Facteurs socioéconomiques , Facteurs de risque
17.
Int Endod J ; 2024 Jun 21.
Article de Anglais | MEDLINE | ID: mdl-39031653

RÉSUMÉ

AIM: This study investigated the effects of the inflammatory microenvironment of moderate pulpitis on biological properties of human dental pulp stem cells (DPSCs) and further explored the mechanism involved in osteo-/odontogenic induction of the inflammatory microenvironment. METHODOLOGY: Healthy DPSCs (hDPSCs) and inflammatory DPSCs (iDPSCs) were isolated from human-impacted third molars free of caries and clinically diagnosed with moderate pulpitis, respectively. Healthy DPSCs were treated with lipopolysaccharides (LPS) to mimic iDPSCs in vitro. The surface markers expressed on hDPSCs and iDPSCs were detected by flow cytometry. A CCK-8 assay was performed to determine cell proliferation. Flow cytometric analysis was used to evaluate cell apoptosis. The osteo-/odontogenic differentiation of DPSCs was evaluated by western blot, alkaline phosphatase staining, and Alizarin Red S staining. The functions of the genes of differentially expressed mRNAs of hDPSCs and iDPSCs were analysed using gene set enrichment analysis. Transmission electron microscopy and western blot were used to evaluate the autophagy changes of LPS-treated DPSCs. RESULTS: Compared with hDPSCs, iDPSCs showed no significant difference in proliferative capacity but had stronger osteo-/odontogenic potential. In addition, the mRNAs differentially expressed between iDPSCs and hDPSCs were considerably enriched in autophagosome formation and assembly-related molecules. In vitro mechanism studies further found that low concentrations of LPS could upregulate DPSC autophagy-related protein expression and autophagosome formation and promote its odontogenic/osteogenic differentiation, whereas the inhibition of DPSC autophagy led to the weakening of the odontogenic/osteogenic differentiation induced by LPS. CONCLUSIONS: This explorative study showed that DPSCs isolated from teeth with moderate pulpitis possessed higher osteo-/odontogenic differentiation capacity, and the mechanism involved was related to the inflammatory microenvironment-mediated autophagy of DPSCs. This helps to better understand the repair potential of inflamed dental pulp and provides the biological basis for pulp preservation and hard tissue formation in minimally invasive endodontics.

18.
Proc Natl Acad Sci U S A ; 121(28): e2403143121, 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38959041

RÉSUMÉ

Currently, the nanofluidic synapse can only perform basic neuromorphic pulse patterns. One immediate problem that needs to be addressed to further its capability of brain-like computing is the realization of a nanofluidic spiking device. Here, we report the use of a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate membrane to achieve bionic ionic current-induced spiking. In addition to the simulation of various electrical pulse patterns, our synapse could produce transmembrane ionic current-induced spiking, which is highly analogous to biological action potentials with similar phases and excitability. Moreover, the spiking properties could be modulated by ions and neurochemicals. We expect that this work could contribute to biomimetic spiking computing in solution.


Sujet(s)
Potentiels d'action , Polystyrènes , Synapses , Potentiels d'action/physiologie , Synapses/physiologie , Polystyrènes/composition chimique , Nanotechnologie/méthodes , Nanotechnologie/instrumentation
19.
Zhen Ci Yan Jiu ; 49(7): 777-786, 2024 Jul 25.
Article de Anglais, Chinois | MEDLINE | ID: mdl-39020497

RÉSUMÉ

OBJECTIVES: Scalp acupuncture is a method of treating diseases by dividing and stimulating the corresponding function-oriented cortical scalp areas. It is a commonly used therapy for neurological disorders. However, the specific target selection for scalp acupuncture remains to be explored. This manuscript aims to initiate an attempt to develop/identify scalp acupuncture targets based on neuroimaging findings and noninvasive brain stimulation. METHODS: Neurosynth-based meta-analysis of neuroimaging studies was conducted to identify brain stimulation targets of neurological disorders. The identified target regions were further projected to the scalp. The traditional acupoints and 10-20 EEG system were referenced for the localization of these targets. In this study, the "mild cognitive impairment" (MCI), "Alzheimer's disease" (AD) and "dementia" were used as the retrieval terms respectively, and a unity detection method was used to generate brain maps, with the default FDR (false discovery rate, P<0.01) threshold of Neurosynth set for subsequent exploration of various disease-related brain regions. The literature search was conducted on July 30, 2022. RESULTS: The localization and manipulation suggestions of neuroimage-based scalp acupuncture targets for MCI, AD, and dementia were introduced in the present paper (part 2). Here are 3 target examples for each of these 3 diseases due to word limitation. 1) MCI:Based on the 81 papers retrieved, we identified 6 potential scalp acupuncture points for MCI, their corresponding brain regions, brain functions and the possible resultant effects of the scalp target acupoint stimulation respectively are as below. MCI1:the orbital part of the left inferior frontal gyrus (left Brodmann area [BA]47), related to semantic coding, working memory and episodic memory, improving semantic coding and memory function;MCI2:the anterior motor area/left anterior central gyrus (left BA6), the motor center area, improving MCI motor function;MCI3:the left medial temporal gyrus (left BA21), related to the processing of speech, visual space, language and word understanding, improving language and memory. 2) AD:Based on the 196 papers retrieved, we found 6 potential scalp acupuncture targets for AD, their corresponding brain regions and brain functions of the 3 example targets respectively are as below. AD1:the left medial temporal gyrus (left BA21), participating in language and semantic processing, sentence and word generation, intent expression, deductive reasoning;AD2:the left angular gyrus (left BA39), related to semantic processing, word reading and comprehension, memory retrieval, attention and spatial cognition, reasoning, etc.;AD3:the left fusiform/suboccipital gyrus (left BA37), related to semantic classification, text generation, sign language, phonology processing, etc. 3) Dementia:Based on the 142 papers retrieved, we found 4 potential scalp acupuncture targets for dementia, their corresponding brain regions, brain functions and the possible targets of the proposed scalp stimulation respectively are as below. D1 and D2:the left inferior frontal gyrus (i.e., left BA46, and left BA47, respectively), being closely related to working memory, emotional response regulation, melody and other processing processes, may be suitable for treating memory decline and advanced executive dysfunction in patients with dementia;D3:the left medial temporal gyrus (left BA21), an important brain region for various sensory integration, cognitive processing and memory functions, and emotional processing, may be suitable for temporal dementia. CONCLUSIONS: We identified scalp acupuncture targets for several common neurological disorders based on neuroimaging findings and noninvasive brain stimulation. The proposed targets may also be used for treating these disorders using nerve/brain stimulation methods.


Sujet(s)
Thérapie par acupuncture , Maladies du système nerveux , Neuroimagerie , Cuir chevelu , Humains , Neuroimagerie/méthodes , Maladies du système nerveux/thérapie , Maladies du système nerveux/imagerie diagnostique , Points d'acupuncture , Encéphale/imagerie diagnostique , Encéphale/physiopathologie , Dysfonctionnement cognitif/thérapie , Dysfonctionnement cognitif/imagerie diagnostique , Dysfonctionnement cognitif/physiopathologie , Maladie d'Alzheimer/thérapie , Maladie d'Alzheimer/imagerie diagnostique
20.
Adv Mater ; 36(38): e2405887, 2024 Sep.
Article de Anglais | MEDLINE | ID: mdl-39054924

RÉSUMÉ

Reproducing human visual functions with artificial devices is a long-standing goal of the neuromorphic domain. However, emulating the chemical language communication of the visual system in fluids remains a grand challenge. Here, a "multi-color" hydrogel-based photoelectrochemical retinomorphic synapse is reported with unique chemical-ionic-electrical signaling in an aqueous electrolyte that enables, e.g., color perception and biomolecule-mediated synaptic plasticity. Based on the specific enzyme-catalyzed chromogenic reactions, three multifunctional colored hydrogels are developed, which can not only synergize with the Bi2S3 photogate to recognize the primary colors but also synergize with a given polymeric channel to promote the long-term memory of the system. A synaptic array is further constructed for sensing color images and biomolecule-coded information communication. Taking advantage of the versatile biochemistry, the biochemical-driven reversible photoelectric response of the cone cell is further mimicked. This work introduces rich chemical designs into retinomorphic devices, providing a perspective for replicating the human visual system in fluids.


Sujet(s)
Hydrogels , Synapses , Hydrogels/composition chimique , Humains , Synapses/métabolisme , Processus photochimiques
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