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1.
Int J Paediatr Dent ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38725105

RESUMEN

BACKGROUND: Changes in healthy and inflamed pulp on periapical radiographs are traditionally so subtle that they may be imperceptible to human experts, limiting its potential use as an adjunct clinical diagnostic feature. AIM: This study aimed to investigate the feasibility of an image-analysis technique based on the convolutional neural network (CNN) to detect irreversible pulpitis in primary molars on periapical radiographs (PRs). DESIGN: This retrospective study was performed in two health centres. Patients who received indirect pulp therapy at Peking University Hospital for Stomatology were retrospectively identified and randomly divided into training and validation sets (8:2). Using PRs as input to an EfficientNet CNN, the model was trained to categorise cases into either the success or failure group and externally tested on patients who presented to our affiliate institution. Model performance was evaluated using sensitivity, specificity, accuracy and F1 score. RESULTS: A total of 348 PRs with deep caries were enrolled from the two centres. The deep learning model achieved the highest accuracy of 0.90 (95% confidence interval: 0.79-0.96) in the internal validation set, with an overall accuracy of 0.85 in the external test set. The mean greyscale value was higher in the failure group than in the success group (p = .013). CONCLUSION: The deep learning-based model could detect irreversible pulpitis in primary molars with deep caries on PRs. Moreover, this study provides a convenient and complementary method for assessing pulp status.

2.
Chem Commun (Camb) ; 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38726610

RESUMEN

For the first time, a novel donor-acceptor structured COF with excellent photothermal conversion and mono-dispersity in various oils without any further modification is reported; it realized responsive friction reduction, excellent antiwear and long-time lubrication.

3.
J Phys Chem Lett ; : 5618-5624, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758202

RESUMEN

Iodine-doped bromide perovskite single crystals (IBPSCs) have important applications in optoelectronic fields, such as in solar cells. Currently, much research has aimed to study the phase separation phenomenon and device performance improvements in IBPSCs. However, important intrinsic photoexcited carrier dynamics are often overlooked in IBPSCs. Here, we explored the photoexcited carrier dynamics in typical iodine-doped MAPbBr3 single crystals using the excitation intensity-dependent steady-state photoluminescence (PL) and time-resolved photoluminescence (TRPL) technique. We found that the trap state density changes with an increase in the amount of doped iodine. Further, we noticed that there is an influence of carrier diffusion on the photoexcited carrier dynamics, and then, we evaluated the carrier diffusion coefficients and recombination constants via numerical simulations of the PL kinetics. Consequently, we found that the electron shallow trap-related carrier behaviors substantially impacted the PL kinetics. Our results greatly facilitate a deeper understanding of the fundamental characteristics of mixed halide perovskite material.

4.
Plants (Basel) ; 13(9)2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38732492

RESUMEN

Tomato yellow leaf curl virus (TYLCV) is a prominent viral pathogen that adversely affects tomato plants. Effective strategies for mitigating the impact of TYLCV include isolating tomato plants from the whitefly, which is the vector of the virus, and utilizing transgenic lines that are resistant to the virus. In our preliminary investigations, we observed that the use of growth retardants increased the rate of TYLCV infection and intensified the damage to the tomato plants, suggesting a potential involvement of gibberellic acid (GA) in the conferring of resistance to TYLCV. In this study, we employed an infectious clone of TYLCV to inoculate tomato plants, which resulted in leaf curling and growth inhibition. Remarkably, this inoculation also led to the accumulation of GA3 and several other phytohormones. Subsequent treatment with GA3 effectively alleviated the TYLCV-induced leaf curling and growth inhibition, reduced TYLCV abundance in the leaves, enhanced the activity of antioxidant enzymes, and lowered the reactive oxygen species (ROS) levels in the leaves. Conversely, the treatment with PP333 exacerbated TYLCV-induced leaf curling and growth suppression, increased TYLCV abundance, decreased antioxidant enzyme activity, and elevated ROS levels in the leaves. The analysis of the gene expression profiles revealed that GA3 up-regulated the genes associated with disease resistance, such as WRKYs, NACs, MYBs, Cyt P450s, and ERFs, while it down-regulated the DELLA protein, a key agent in GA signaling. In contrast, PP333 induced gene expression changes that were the opposite of those caused by the GA3 treatment. These findings suggest that GA plays an essential role in the tomato's defense response against TYLCV and acts as a positive regulator of ROS scavenging and the expression of resistance-related genes.

5.
Heliyon ; 10(9): e29652, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38707449

RESUMEN

Background: Current treatments for primary Sjögren's Syndrome (pSS) are with limited effect, partially due to the heterogeneity and uncleared mechanism. Methods: We got GSE40568 (Japan) and GSE40611 (USA), and analyzed them with WGCNA to find key Differentially expressed genes (DEGs) between pSS and healthy salivary glands (SG). Key pSS genes (KPGs) were further selected through 3 machine-learning methods. The expression of KPGs was validated via two other GEO datasets (GSE127952 and GSE154926). Infiltrated immune cells, ceRNA network, and potential compounds were explored. Results: Our study identified 376 DEGs from the pSS patients, with 186 genes located in the "plum2" module, showing the strongest correlation with clinical characteristics. SAMD9 and IFIT3 emerged as KPGs with excellent diagnostic potential. SAMD9 demonstrated close association with immune cell infiltration. We constructed a lncRNA-miRNA-mRNA network comprising 2 KPGs, 12 miRNAs, 124 lncRNAs, and potential therapeutic targets. Conclusion: In the investigation of pSS public datasets, our study revealed two potential critical mediators in the pathological process of pSS salivary glands, namely SAMD9 and IFIT3. Furthermore, we put forth a hypothesis regarding the ceRNA network and made predictions regarding potential therapeutic drugs targeting these two genes.

6.
Int J Biol Macromol ; 269(Pt 1): 131994, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38697431

RESUMEN

Nowadays, dye water pollution is becoming increasingly severe. Composite of MXene, ZnS, and chitosan-cellulose material (MX/ZnS/CC) was developed to remove anionic dyes through the synergistic effect of adsorption and photocatalytic degradation. MXene was introduced as the cocatalyst to form Schottky heterostructure with ZnS for improving the separation efficiency of photocarriers and photocatalytic performance. Chitosan-cellulose material mainly served as the dye adsorbent, while also could improve material stability and assist in generation of free radicals for dye degradation. The physics and chemistry properties of MX/ZnS/CC composite were systematically inspected through various characterizations. MX/ZnS/CC composite exhibited good adsorption ability to anionic dyes with adsorption capacity up to 1.29 g/g, and excellent synergistic effects of adsorption and photodegradation with synergistic removal capacity up to 5.63 g/g. MX/ZnS/CC composite performed higher synergistic removal ability and better optical and electrical properties than pure MXene, ZnS, chitosan-cellulose material, and MXene/ZnS. After compounding, the synergistic removal percentage of dyes increased by a maximum of 309 %. MX/ZnS/CC composite mainly adsorbs anionic dyes through electrostatic interactions and catalyzes the generation of •O2-, h+, and •OH to degrade dyes, which has been successfully used to remove anionic dyes from environmental water, achieving a 100 % removal of 50 mg/L dye.

7.
J Psychiatr Res ; 175: 20-28, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38701608

RESUMEN

Cell-free DNA (cfDNA) has been found to be elevated in patients with schizophrenia (SZ), potentially derived from activated apoptosis, but the underlying mechanisms remain unknown. Moreover, whether the concentrations of cfDNA are altered with disease stage has not been investigated, which limits its clinical application as an auxiliary diagnostic marker for SZ. Using an improved fluorescence correlation spectroscopy (FCS) method that does not require DNA extraction, we measured the molar concentrations of cfDNA in plasma samples of 191 patients with SZ, 78 patients with mood disorders (MD) and 65 healthy controls (HC). We also analyzed the cfDNA composition from either the nucleus or mitochondria, oxidation markers and biochemical indexes to explore the potential mechanistic associations of the increased cfDNA levels. We found that in SZ patients, the cfDNA levels were significantly increased (P = 0.003) regardless of the different disease stages or antipsychotic medication use. Furthermore, qPCR revealed that cell-free nuclear DNA (cf-nDNA) (P = 0.041) but not cell-free mitochondrial DNA (cf-mtDNA) was elevated in SZ patients. Moreover, decreased SOD activity in SZ patients (P = 0.005) was negatively correlated with cfDNA levels (P = 0.047), and fasting blood glucose was positively correlated with cfDNA levels in SZ patients (P = 0.013). Our study provides evidence to support that the elevated cfDNA may be a convenient, effective and stable trait indicator of SZ. Further analysis showed that it mainly came from nucleus, suggesting increased apoptosis, and potentially related to oxidative stress and high blood glucose levels in patients.

8.
Bioact Mater ; 38: 399-410, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38774457

RESUMEN

Mesenchymal stem cell (MSC) migration determines the healing capacity of bone and is crucial in promoting bone regeneration. Migration of MSCs is highly dependent on degradation of extracellular matrix by proteolytic enzymes. However, the underlying mechanisms of how enzymolysis paves the way for MSCs to migrate from their niche to the defect area is still not fully understood. Here, this study shows that high-temperature requirement A3 (HtrA3) overcomes the physical barrier and provides anchor points through collagen IV degradation, paving the way for MSC migration. HtrA3 is upregulated in MSCs at the leading edge of bone defect during the early stage of healing. HtrA3 degrades the surrounding collagen IV, which increases the collagen network porosity and increases integrin ß1 expression. Subsequently, integrin ß1 enhances the mechanotransduction of MSCs, thus remodeling the cytoskeleton, increasing cellular stiffness and nuclear translocation of YAP, eventually promoting the migration and subsequent osteogenic differentiation of MSCs. Local administration of recombinant HtrA3 in rat cranial bone defects significantly increases new bone formation and further validates the enhancement of MSC migration. This study helps to reveal the novel roles of HtrA3, explore potential targets for regenerative medicine, and offer new insights for the development of bioactive materials.

9.
J Ethnopharmacol ; : 118372, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38777084

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Neovessels represent a crucial therapeutic target and strategy for repairing ischemic tissue. Taohong Siwu Decoction (THSWD) exhibits potential in promoting angiogenesis to address ischemic stroke (IS). However, its impact on neovessel structure and function, alongside the underlying molecular mechanisms, remains elusive. AIM OF THE STUDY: Our aim is to investigate the protective effects of THSWD on neovessel structure and function, as well as the associated molecular mechanisms, utilizing an integrative pharmacological approach. MATERIALS AND METHODS: We initially employed behavioral tests, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Haematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), Laser Doppler flowmetry (LDF), Evans blue staining, and immunofluorescence to evaluate the protective effects of THSWD on neovascular structure and function in middle cerebral artery occlusion/reperfusion (MCAO/R) rats. Subsequently, we utilized network pharmacology, metabolomics, and experimental validation to elucidate the underlying molecular mechanisms of THSWD in enhancing neovascular structure and function. RESULT: In addition to significantly reducing neurological deficits and cerebral infarct volume, THSWD mitigated pathological damage, blood-brain barrier (BBB) leakage, and cerebral blood flow disruption. Moreover, it preserved neovascular structure and stimulated angiogenesis. THSWD demonstrated potential in ameliorating cerebral microvascular metabolic disturbances including lipoic acid metabolism, fructose and mannose metabolism, purine metabolism, and ether lipid metabolism. Consequently, it exhibited multifaceted therapeutic effects, encompassing anti-inflammatory, antioxidant, energy metabolism modulation, and antiplatelet aggregation properties. CONCLUSION: THSWD exhibited protective effects on cerebral vascular structure and function and facilitated angiogenesis by rectifying cerebral microvascular metabolic disturbances in MCAO/R rats. Furthermore, integrated pharmacology offers a promising approach for studying the intricate traditional Chinese medicine (TCM) system in IS treatment.

10.
Clinics (Sao Paulo) ; 79: 100372, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38733688

RESUMEN

OBJECTIVE: This study aims to analyze the relationship between the Kelch-like ECH-associated protein 1 (Keap1)/Nuclear factor-erythroid 2-related factor 2 (Nrf2) and Epilepsy (EP), as well as its mechanism of action. METHODS: Thirty Wistar rats were divided into a control group (without treatment), a model group (EP modeling), and an inhibition group (EP modeling + intervention by Keap1/Nrf2 signaling pathway inhibitor ATRA) and subject to Morris water maze experiment. Then, the expression of Oxidative Stress (OS) markers, ferroptosis-associated proteins and Keap1/Nrf2 pathway in rat hippocampus was measured. In addition, rat hippocampal neuronal cell HT22 was purchased and treated accordingly based on the results of grouping, and cell proliferation and apoptosis in the three groups were determined. RESULTS: Compared with rats in the model group, those in the inhibition group showed shorter escape latency and an increased number of platform crossings (p < 0.05). Significant OS and neuron ferroptosis, increased apoptosis rate, elevated Keap1 expression, and decreased Nrf2 expression were observed in the model group compared to the control group (p < 0.05). The inhibition group exhibited notably improved OS and ferroptosis, as well as enhanced neuronal viability (p < 0.05). CONCLUSION: Inhibition of the Keap1/Nrf2 pathway can reverse the OS and neuron viability in EP rats.


Asunto(s)
Epilepsia , Ferroptosis , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2 , Neuronas , Estrés Oxidativo , Ratas Wistar , Transducción de Señal , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/fisiología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Estrés Oxidativo/fisiología , Transducción de Señal/fisiología , Ferroptosis/fisiología , Ferroptosis/efectos de los fármacos , Neuronas/metabolismo , Epilepsia/metabolismo , Epilepsia/fisiopatología , Masculino , Hipocampo/metabolismo , Apoptosis/fisiología , Ratas , Progresión de la Enfermedad , Modelos Animales de Enfermedad
11.
Microbiol Res ; 285: 127748, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38735241

RESUMEN

The rhizosphere system of plants hosts a diverse consortium of bacteria that confer beneficial effects on plant, such as plant growth-promoting rhizobacteria (PGPR), biocontrol agents with disease-suppression activities, and symbiotic nitrogen fixing bacteria with the formation of root nodule. Efficient colonization in planta is of fundamental importance for promoting of these beneficial activities. However, the process of root colonization is complex, consisting of multiple stages, including chemotaxis, adhesion, aggregation, and biofilm formation. The secondary messenger, c-di-GMP (cyclic bis-(3'-5') dimeric guanosine monophosphate), plays a key regulatory role in a variety of physiological processes. This paper reviews recent progress on the actions of c-di-GMP in plant beneficial bacteria, with a specific focus on its role in chemotaxis, biofilm formation, and nodulation.

12.
Langmuir ; 40(19): 10059-10069, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38700229

RESUMEN

Due to its ultrahigh theoretical capacitance, vanadium pentoxide (V2O5) is considered to be a valid candidate for advanced supercapacitors. However, because of the low electron/electrolyte transfer rate, the capacitive performance still remains to be improved. In this report, Cu doping is adopted to improve the capacitive performance by a two-steps strategy consisting of microwave-assisted solvothermal and postannealing treatments. The electrochemical results indicate that the Cu doping was beneficial for improving the specific capacitance, extending the potential window, and improving the rate ability and long-term stability of V2O5. Furthermore, the mechanism for the performance improvement is explained in detail by combining theoretical calculation and experiments. The results indicated that, compared with that of undoped V2O5, the larger interplanar spacing, better electrical conductivity, a larger proportion of V3+/V4+, and more abundant oxygen vacancies result in an improved capacitive performance. Our proposed Cu-doped V2O5 (Cu-V2O5) can be used as both a positive electrode and a negative electrode for the assembly of the symmetric supercapacitor, which can be used as an energy storage device for light emitting diode lamps.

13.
ACS Nano ; 18(20): 13249-13265, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38720584

RESUMEN

The therapeutic application of mesenchymal stem cells (MSCs) has good potential as a treatment strategy for systemic lupus erythematosus (SLE), but traditional MSC therapy still has limitations in effectively modulating immune cells. Herein, we present a promising strategy based on dexamethasone liposome-integrated MSCs (Dexlip-MSCs) for treating SLE via multiple immunomodulatory pathways. This therapeutic strategy prolonged the circulation time of dexamethasone liposomes in vivo, restrained CD4+T-cell proliferation, and inhibited the release of proinflammatory mediators (IFN-γ and TNF-α) by CD4+T cells. In addition, Dexlip-MSCs initiated cellular reprogramming by activating the glucocorticoid receptor (GR) signaling pathway to upregulate the expression of anti-inflammatory factors such as cysteine-rich secretory protein LCCL-containing domain 2 (CRISPLD2) and downregulate the expression of proinflammatory factors. In addition, Dexlip-MSCs synergistically increased the anti-inflammatory inhibitory effect of CD4+T cells through the release of dexamethasone liposomes or Dex-integrated MSC-derived exosomes (Dex-MSC-EXOs). Based on these synergistic biological effects, we demonstrated that Dexlip-MSCs alleviated disease progression in MRL/lpr mice more effectively than Dexlip or MSCs alone. These features indicate that our stem cell delivery strategy is a promising therapeutic approach for clinical SLE treatment.


Asunto(s)
Dexametasona , Lupus Eritematoso Sistémico , Células Madre Mesenquimatosas , Animales , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Dexametasona/farmacología , Dexametasona/química , Lupus Eritematoso Sistémico/terapia , Lupus Eritematoso Sistémico/inmunología , Ratones , Liposomas/química , Trasplante de Células Madre Mesenquimatosas , Proliferación Celular/efectos de los fármacos , Femenino , Ratones Endogámicos MRL lpr , Humanos , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Antiinflamatorios/farmacología , Antiinflamatorios/química
14.
Sci Total Environ ; 932: 172927, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38719057

RESUMEN

Tire-derived rubber crumbs (RC), as a new type of microplastics (MPs), harms both the environment and human health. Excessive use of plastic, the decomposition of which generates microplastic particles, in current agricultural practices poses a significant threat to the sustainability of agricultural ecosystems, worldwide food security and human health. In this study, the application of biochar, a carbon-rich material, to soil was explored, especially in the evaluation of synthetic biochar-based community (SynCom) to alleviate RC-MP-induced stress on plant growth and soil physicochemical properties and soil microbial communities in peanuts. The results revealed that RC-MPs significantly reduced peanut shoot dry weight, root vigor, nodule quantity, plant enzyme activity, soil urease and dehydrogenase activity, as well as soil available potassium, and bacterial abundance. Moreover, the study led to the identification highly effective plant growth-promoting rhizobacteria (PGPR) from the peanut rhizosphere, which were then integrated into a SynCom and immobilized within biochar. Application of biochar-based SynCom in RC-MPs contaminated soil significantly increased peanut biomass, root vigor, nodule number, and antioxidant enzyme activity, alongside enhancing soil enzyme activity and rhizosphere bacterial abundance. Interestingly, under high-dose RC-MPs treatment, the relative abundance of rhizosphere bacteria decreased significantly, but their diversity increased significantly and exhibited distinct clustering phenomenon. In summary, the investigated biochar-based SynCom proved to be a potential soil amendment to mitigate the deleterious effects of RC-MPs on peanuts and preserve soil microbial functionality. This presents a promising solution to the challenges posed by contaminated soil, offering new avenues for remediation.


Asunto(s)
Arachis , Carbón Orgánico , Microplásticos , Microbiología del Suelo , Contaminantes del Suelo , Suelo , Carbón Orgánico/química , Arachis/microbiología , Contaminantes del Suelo/análisis , Suelo/química , Microbiota , Rizosfera , Restauración y Remediación Ambiental/métodos
15.
Int J Rheum Dis ; 27(5): e15166, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38720417

RESUMEN

OBJECTIVES: To identify the effectiveness and safety of inactivated SARS-CoV-2 vaccines in rheumatic and musculoskeletal diseases (RMDs) patients. METHODS: RMD patients with COVID-19 in Jiangsu Province were polled between December 8, 2022, and February 1, 2023. Information on demographics, disease characteristics, antirheumatic drug use, vaccination status and survival state were collected. COVID-19-associated pneumonia was the primary outcome. The effect of COVID-19 immunization on RMD patients was assessed using multivariate logistic regression, and the adverse events (AEs) following vaccination were evaluated. RESULTS: Among 592 RMD patients with COVID-19, 276 (46.6%) individuals experienced COVID-19-associated pneumonia, and 290 (49.0%) patients were injected with inactivated vaccines. In multivariate logistic regression analysis, vaccines reduced the incidence of COVID-19-associated pneumonia, and receiving booster vaccine was an independent protective factor for COVID-19-associated pneumonia in RMD patients (OR 0.64, 95% CI 0.41-0.98, p = .034). In particular, inactivated vaccines have a protective impact on RMD patients with a high risk of developing pneumonia, including those aged 45 years and older (OR 0.53, 95% CI 0.34-0.83), and who have lung involvement (OR 0.43, 95% CI 0.23-0.82). The total AEs rate of vaccines was 13.9% (40/290), only 11 (3.8%) experienced the recurrence or deterioration of RMDs, and no serious AEs occurred. CONCLUSION: Inactivated COVID-19 vaccines were safe and effective in reducing the risk of COVID-19-associated pneumonia of RMD patients in China.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Enfermedades Musculoesqueléticas , Enfermedades Reumáticas , Vacunas de Productos Inactivados , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Enfermedades Reumáticas/inmunología , Enfermedades Reumáticas/tratamiento farmacológico , Enfermedades Reumáticas/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , Enfermedades Musculoesqueléticas/diagnóstico , Enfermedades Musculoesqueléticas/epidemiología , Vacunas de Productos Inactivados/efectos adversos , Anciano , Adulto , SARS-CoV-2/inmunología , China/epidemiología , Eficacia de las Vacunas , Resultado del Tratamiento , Factores de Riesgo
16.
Int J Rheum Dis ; 27(5): e15164, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38706209

RESUMEN

BACKGROUND: JAK inhibitors are well known for the treatment of rheumatoid arthritis (RA), but whether they can be used to treat pulmonary fibrosis, a common extra-articular disease of RA, remains to be clarified. METHODS: A jak2 inhibitor, CEP33779 (CEP), was administered to a rat model of RA-associated interstitial lung disease to observe the degree of improvement in both joint swelling and pulmonary fibrosis. HFL1 cells were stimulated with TGF-ß1 to observe the expression of p-JAK2. Then, different concentrations of related gene inhibitors (JAK2, TGFß-R1/2, and p-STAT3) or silencers (STAT3, JAK2) were administered to HFL1 cells, and the expression levels of related proteins were detected to explore the underlying mechanisms of action. RESULTS: CEP not only reduced the degree of joint swelling and inflammation in rats but also improved lung function, inhibited the pro-inflammatory factors IL-1ß and IL-6, reduced lung inflammation and collagen deposition, and alleviated lung fibrosis. CEP decreased the expression levels of TGFß-R2, p-SMAD, p-STAT3, and ECM proteins in rat lung tissues. TGF-ß1 induced HFL1 cells to highly express p-JAK2, with the most pronounced expression at 48 h. The levels of p-STAT3, p-SMAD3, and ECM-related proteins were significantly reduced after inhibition of either JAK2 or STAT3. CONCLUSION: JAK2 inhibitors may be an important and novel immunotherapeutic drug that can improve RA symptoms while also delaying or blocking the development of associated pulmonary fibrotic disease. The mechanism may be related to the downregulation of p-STAT3 protein via inhibition of the JAK2/STAT signaling pathway, which affects the phosphorylation of SMAD3.


Asunto(s)
Modelos Animales de Enfermedad , Regulación hacia Abajo , Isoquinolinas , Janus Quinasa 2 , Pulmón , Fibrosis Pulmonar , Piridinas , Pirroles , Transducción de Señal , Proteína smad3 , Animales , Proteína smad3/metabolismo , Fibrosis Pulmonar/tratamiento farmacológico , Fibrosis Pulmonar/metabolismo , Janus Quinasa 2/metabolismo , Janus Quinasa 2/antagonistas & inhibidores , Fosforilación , Transducción de Señal/efectos de los fármacos , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Pulmón/enzimología , Masculino , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/metabolismo , Humanos , Ratas Sprague-Dawley , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/uso terapéutico , Línea Celular , Inhibidores de Proteínas Quinasas/farmacología , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/metabolismo , Artritis Experimental/enzimología , Antiinflamatorios/farmacología , Ratas
17.
Artículo en Inglés | MEDLINE | ID: mdl-38701878

RESUMEN

BACKGROUND: Anhedonia, a core symptom of major depressive disorder (MDD), manifests in two forms: anticipatory and consummatory, reflecting a diminished capacity to anticipate or enjoy pleasurable activities. Prior studies suggest that brain-derived neurotrophic factor (BDNF) and interleukin-10 (IL-10) may play key roles in the emergence of anhedonia in MDD. The specific relationships between these biomarkers and the two forms of anhedonia remain unclear. This study investigated the potential links between BDNF, IL-10, and both forms of anhedonia in MDD patients. METHODS: This study included 43 participants diagnosed with MDD and 58 healthy controls. It involved detailed assessments of depression and anxiety levels, anticipatory and consummatory pleasure, cognitive functions, and a broad spectrum of plasma biomarkers, such as C-reactive protein, various interleukins, and BDNF. Using partial correlation, variables related to pleasant experiences were identified. Stepwise multiple linear regression analysis was applied to pinpoint the independent predictors of anhedonia in the MDD group. RESULTS: Demographically, both groups were comparable in terms of age, sex, body mass index, educational year, and marital status. Individuals with MDD displayed markedly reduced levels of anticipatory and consummatory pleasure, higher anxiety, and depression scores compared to healthy controls. Additionally, cognitive performance was notably poorer in the MDD group. These patients also had lower plasma diamine oxidase levels. Analysis linked anhedonia to impaired delayed memory. Regression results identified IL-10 and BDNF as independent predictors of anticipatory and consummatory anhedonia, respectively. CONCLUSION: These findings demonstrate that anticipatory and consummatory anhedonia are influenced by independent factors, thereby providing critical insights into the distinct neuroimmunological mechanisms that underlie various forms of anhedonia. Clinicl Trial Registration Number: NCT03790085.

18.
Cell ; 187(10): 2359-2374.e18, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38653240

RESUMEN

Brown adipose tissue (BAT) is best known for thermogenesis. Rodent studies demonstrated that enhanced BAT thermogenesis is tightly associated with increased energy expenditure, reduced body weight, and improved glucose homeostasis. However, human BAT is protective against type 2 diabetes, independent of body weight. The mechanism underlying this dissociation remains unclear. Here, we report that impaired mitochondrial catabolism of branched-chain amino acids (BCAAs) in BAT, by deleting mitochondrial BCAA carriers (MBCs), caused systemic insulin resistance without affecting energy expenditure and body weight. Brown adipocytes catabolized BCAA in the mitochondria as nitrogen donors for the biosynthesis of non-essential amino acids and glutathione. Impaired mitochondrial BCAA-nitrogen flux in BAT resulted in increased oxidative stress, decreased hepatic insulin signaling, and decreased circulating BCAA-derived metabolites. A high-fat diet attenuated BCAA-nitrogen flux and metabolite synthesis in BAT, whereas cold-activated BAT enhanced the synthesis. This work uncovers a metabolite-mediated pathway through which BAT controls metabolic health beyond thermogenesis.


Asunto(s)
Tejido Adiposo Pardo , Aminoácidos de Cadena Ramificada , Resistencia a la Insulina , Mitocondrias , Nitrógeno , Termogénesis , Tejido Adiposo Pardo/metabolismo , Animales , Aminoácidos de Cadena Ramificada/metabolismo , Ratones , Nitrógeno/metabolismo , Mitocondrias/metabolismo , Masculino , Humanos , Metabolismo Energético , Ratones Endogámicos C57BL , Estrés Oxidativo , Insulina/metabolismo , Dieta Alta en Grasa , Adipocitos Marrones/metabolismo , Transducción de Señal
19.
Ophthalmol Ther ; 13(6): 1527-1535, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38581607

RESUMEN

INTRODUCTION: The aim of this work is to investigate the dynamic changes of capsular-intraocular lens (IOL) adhesion in plate-haptic hydrophilic and loop-haptic hydrophobic eyes. METHODS: Cataract eyes that met the inclusion criteria were randomly assigned to receive implantation of a plate-haptic hydrophilic or loop-haptic IOL. The anterior capsular adhesion, posterior capsular adhesion, and the configurations of the capsular bend were evaluated using swept-source optical coherence tomography at 1 day, 1 week, 1 month, and 3 months postoperatively. RESULTS: In total, 66 eyes of 66 patients were eligible for the analysis: 33 in the plate-haptic group and 33 in the loop-haptic group. The contact between the anterior capsule and IOL in the plate-haptic group was earlier than that in the loop-haptic group upon comparing the measurements taken at 1 day and 1 week (p = 0.001, p = 0.003, respectively). The complete attachment of the posterior capsule and IOL in the plate-haptic group was significantly greater at 1 week, 1 month, and 3 months (p = 0.001, p = 0.000, p = 0.001, respectively). The capsular bend index of the plate-haptic group was significantly greater than that of the loop-haptic group at each time points except at 1 day (p = 0.007, p = 0.049, p = 0.005, respectively). Furthermore, a new type of capsular bend, "cocked adhesion," was observed in the plate-haptic eyes. CONCLUSIONS: The plate-haptic IOL demonstrated excellent capsular adhesion compared to the loop-haptic IOL, which was probably attributed to haptic compressibility. A special cocked configuration of the capsular bend in plate-haptic IOL was observed for the first time. Further studies are warranted to confirm the effect of the new type of capsular bend.

20.
Arch Virol ; 169(5): 89, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565720

RESUMEN

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and high mortality in neonatal suckling piglets, leading to significant economic losses to the swine industry. Panax notoginseng saponins (PNS) are bioactive extracts derived from the P. notoginseng plant. In this study, we investigated the anti-PEDV effect of PNS by employing various methodologies to assess their impact on PEDV in Vero cells. Using a CCK-8 (Cell Counting Kit-8) assay, we found that PNS had no significant cytotoxicity below the concentration of 128 µg/mL in Vero cells. Using immunofluorescence assays (IFAs), an enzyme-linked immunosorbent assay (ELISA), and plaque formation assays, we observed a dose-dependent inhibition of PEDV infection by PNS within 24-48 hours postinfection. PNS exerts its anti-PEDV activity specifically at the genome replication stage, and mRNA-seq analysis demonstrated that treatment with PNS resulted in increased expression of various genes, including IFIT1 (interferon-induced protein with tetratricopeptide repeats 1), IFIT3 (interferon-induced protein with tetratricopeptide repeats 3), CFH (complement factor H), IGSF10 (immunoglobulin superfamily member 10), ID2 (inhibitor of DNA binding 2), SPP1 (secreted phosphoprotein 1), PLCB4 (phospholipase C beta 4), and FABP4 (fatty acid binding protein 4), but it resulted in decreased expression of IL1A (interleukin 1 alpha), TNFRSF19 (TNF receptor superfamily member 19), CDH8 (cadherin 8), DDIT3 (DNA damage inducible transcript 3), GADD45A (growth arrest and DNA damage inducible alpha), PTPRG (protein tyrosine phosphatase receptor type G), PCK2 (phosphoenolpyruvate carboxykinase 2), and ADGRA2 (adhesion G protein-coupled receptor A2). This study provides insights into the potential mechanisms underlying the antiviral effects of PNS. Taken together, the results suggest that the PNS might effectively regulate the defense response to the virus and have potential to be used in antiviral therapies.


Asunto(s)
Infecciones por Coronavirus , Panax notoginseng , Virus de la Diarrea Epidémica Porcina , Saponinas , Enfermedades de los Porcinos , Chlorocebus aethiops , Animales , Porcinos , Saponinas/farmacología , Células Vero , Virus de la Diarrea Epidémica Porcina/genética , Interferones , Antivirales/farmacología , Enfermedades de los Porcinos/tratamiento farmacológico
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