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1.
Front Pharmacol ; 13: 978587, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091773

RESUMO

Background: Neuroinflammation plays a crucial role in the pathogenesis and progression of various neurodegenerative diseases, including Alzheimer's disease. The Ginkgo biloba leaf extract (GBE) has been widely used to treat cerebral and peripheral blood circulation disorders. However, its potential targets and underlying mechanisms regarding neuroinflammation have not yet been characterized. Aims: The purpose of this study was to investigate and validate the anti-neuroinflammatory properties of GBE against lipopolysaccharide (LPS)-mediated inflammation and to determine the underlying molecular mechanisms. Methods: The effect of GBE on LPS-induced release of inflammatory cytokines was examined using ELISA and western blot assay. The effects of GBE on NF-κB binding activity and translocation were determined via luciferase, streptavidin-agarose pulldown, and immunofluorescence assays. The potential targets of GBE were screened from the GEO and microRNA databases and further identified via qPCR, luciferase, gene mutation, and western blot assays. Results: GBE significantly inhibited LPS-induced pro-inflammatory responses in BV-2 and U87 cells, with no obvious cytotoxicity. GBE significantly induced miR-146b-5p expression, which negatively regulated TRAF6 expression by targeting its 3'-UTR. Thus, due to TRAF6 suppression, GBE decreases the transcriptional activity of NF-κB and the expression of pro-inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, and cyclooxygenase (COX)-2, and finally reverses LPS-induced neuroinflammation. Conclusion: Our study revealed the anti-neuroinflammatory mechanism of GBE through the miR-146b-5p/TRAF6 axis and provided a theoretical basis for its rational clinical application.

2.
Front Chem ; 10: 919192, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092657

RESUMO

The Co3O4 nanoparticle-modified indium tin oxide-coated glass slide (ITO) electrodes are successfully prepared using dicarboxylic acid as the self-assembled monolayer through a surface esterification reaction. The ITO-SAM-Co3O4 (SAM = dicarboxylic acid) are active to electrochemically catalyze oxygen evolution reaction (OER) in acid. The most active assembly, with Co loading at 3.31 × 10-8 mol cm-2, exhibits 374 mV onset overpotential and 497 mV overpotential to reach 1 mA cm-2 OER current in 0.1 M HClO4. The electron transfer rate constant (k) is acquired using Laviron's approach, and the results show that k is not affected by the carbon chain lengths of the SAM (up to 18 -CH2 groups) and that an increase in the average diameter of Co3O4 nanoparticles enhances the k. In addition, shorter carbon chains and smaller Co3O4 nanoparticles can increase the turn-over frequency (TOF) of Co sites toward OER. The Co3O4 nanoparticles tethered to the ITO surface show both a higher number of electrochemically active Co sites and a higher TOF of OER than the Co3O4 nanoparticles bound to ITO using Nafion.

3.
Artigo em Inglês | MEDLINE | ID: mdl-36097408

RESUMO

Patients with coronavirus disease 2019 (COVID-19) has been isolated in hospital-managed isolation hotels under a policy of the Taiwan government. Centrally isolation patients are more likely to experience psychological symptoms. The purpose of the study was to investigate emotional disturbance during their isolation period and then pinpoint the factors during their isolation period associated with the emotional disturbance. We retrospectively analysed the medical charts of the patients confined to a Banqiao isolation hotel between May 28 and July 3, 2021. The 5-item brief symptom rating scale (BSRS-5) was used to evaluate emotional disturbance levels. Descriptive and logistic regression was used for the data analysis. In total, 197 complete medical records were reviewed, and of these 84 (42.6%) showed emotional disturbance. The majority of them reported only minor disturbance (n = 49, 58.3%). After controlling for confounding factors, being satisfied about medical information was the only protective factor associated with emotional disturbance (OR = 0.2, P = 0.018). Being a male patient (OR = 3.0, P = 0.005), worrying about stigmatization (OR = 2.2, P = 0.041) and being unable to contact family members (OR = 2.9, P = 0.018) increased the risk of experiencing emotional disturbance. Patients with clinical symptoms, namely sore throat (OR = 3.4, P = 0.013) and muscle aches (OR = 6.3, P = 0.005), were also found to be more likely to report emotional disturbance. Mental disturbance commonly occurs among patient with COVID-19 who are isolated in a hospital-managed hotel. Being a male patient, having symptoms, namely a sore throat and muscle pain, being unable to contact family and/or a failure to receive sufficient medical information were found to be associated with emotional disturbance. In order to help isolated patients, government officials should provide a clear rationale for isolation and recognize the patients' efforts to follow the government's policy, which will help to minimize social stigma.

4.
J Hazard Mater ; 441: 129884, 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36084465

RESUMO

The removal of trivalent arsenic (As (III)) from water has received extensive attention from researchers. Iron electrocoagulation (Fe-EC) is an efficient technology for arsenic removal. However, electrode passivation hinders the development and application of Fe-EC. In this work, an innovative Fe-EC route was developed to remove As (III) through an electrochemical-siderite packed column (ESC). Ferrous ions were produced from siderite near the anode, and hydroxide was generated near the cathode during the electrochemical decomposition of siderite. As a result, an effect of Fe-EC-like was obtained. The results showed that an excellent removal performance of As (III) (>99%) was obtained by adjusting the parameters (As (III) concentration at 10 mg/L, pH at 7, Na2SO4 at 10 mM and the hydraulic retention time at 30 min) and the oxidation rate of As (III) reached 84.12%. The mechanism analysis indicated that As (III) was oxidized to As (Ⅴ) by the produced active oxide species and electrode, and then was removed by capturing on the iron oxide precipitates. As (III) was likely to be oxidized in two ways, one by the reactive oxygen species (possibly •OH, Fe(IV) and •O2- species), and another directly by the anode. The long-term effectiveness of arsenic removal demonstrated that ESC process based on the electrochemical-siderite packed column was an appropriate candidate for treating As (III) pollution.

5.
PLoS One ; 17(9): e0272667, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36103559

RESUMO

In the context of global warming, although the coordinated development of tourism has led to regional economic growth, the high energy consumption-driven effects of such development have also led to environmental degradation. This research combines the undesired output of the Super-SBM model and social network analysis methods to determine the eco-efficiency of provincial tourism in China from 2010-2019 and analyzes its spatial correlation characteristics as well as its influencing factors. The aim of the project is to improve China's regional tourism eco-efficiency and promote cross-regional tourism correlation. The results show that (1) the mean value of provincial tourism eco-efficiency in China is maintained at 0.405~0.612, with an overall fluctuating upward trend. The tourism eco-efficiency of eastern China is higher than that of central, western and northeastern China, but the latter three regions have not formed a stable spatial distribution pattern. (2) The spatial network of provincial tourism eco-efficiency in China is multithreaded, dense and diversified. Throughout the network, affiliations are becoming closer, and network structure robustness is gradually improving, although the "hierarchical" spatial network structure remains. In individual networks, Jiangsu, Guangdong and Shandong provinces in eastern China have higher centrality degrees, closeness centrality and betweenness centrality than other provinces, which means they are dominant in the network. Hainan Province, also located in eastern China, has not yet built a "bridge" for tourism factor circulation. In the core-periphery model, the core-periphery areas of China's provincial tourism eco-efficiency are distributed in clusters, and the number of "core members" has increased. (3) The economic development level, information technology development level, and tourism technology level collectively drive the development and evolution of China's provincial tourism eco-efficiency spatial network.


Assuntos
Carbono , Turismo , China , Desenvolvimento Econômico , Eficiência
6.
J Am Coll Surg ; 235(4): 666-676, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36106868

RESUMO

BACKGROUND: Previous studies on how complete mesocolic excision (CME) affects prognosis indicate fundamental limitations that prevent the procedure from being completely accepted in practice. This study evaluated 5-year survival in colon cancer patients who underwent CME in a strict quality-controlled trial. STUDY DESIGN: A prospective, nonrandomized, double-blind, controlled trial recruited patients who underwent open radical resection for colon cancer between November 2012 and November 2017. Third-party experts evaluated whether patients had undergone mesocolic dissection and/or central ligation by looking at photographs of both surgical field and specimen, and then divided patients into CME and non-CME (NCME) groups. The primary outcome was the 5-year local recurrence-free survival rate. Clinicopathological and follow-up data were recorded. RESULTS: There were 261 patients with a median follow-up time of 57 months assigned to the CME group, and 129 patients with a median follow-up time of 59 months were assigned to the NCME group. The 5-year local recurrence-free survival rate of patients with Union Internationale Contre le Cancer stage I to III cancer did not differ significantly between the groups. For stage I to III cancer and stage III cancer, the absolute risk reduction of 5-year cumulative death and disease progression after CME were 9.1% (95% CI 1% to 17%; p = 0.033) and 16.1% (95% CI 1% to 31%; p = 0.040), respectively. Meanwhile, CME also could reduce 14% 5-year cumulative incidence recurrence for Union Internationale Contre le Cancer stage III cancer compared with NCME (CME, 27.3% vs NCME, 41.3%; p = 0.042) after adjusting for the effect of non-cancer-related death. CONCLUSIONS: CME should be considered as a standard surgical procedure in affected patients.


Assuntos
Neoplasias do Colo , Mesocolo , Colectomia/métodos , Neoplasias do Colo/patologia , Humanos , Mesocolo/patologia , Mesocolo/cirurgia , Prognóstico , Estudos Prospectivos
7.
Acad Radiol ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36117128

RESUMO

OBJECTIVES: To develop and validate an 18F-FDG PET/CT-based radiomics nomogram and evaluate the value of the 18F-FDG PET/CT-based radiomics nomogram for the diagnosis of bone marrow involvement (BMI) in pediatric neuroblastoma. MATERIALS AND METHODS: A total of 144 patients with neuroblastoma (100 in the training cohort and 44 in the validation cohort) were retrospectively included. The PET/CT images of patients were visually assessed. The results of bone marrow aspirates or biopsies were used as the gold standard for BMI. Radiomics features and conventional PET parameters were extracted using the 3D slicer. Features were selected by the least absolute shrinkage and selection operator regression, and radiomics signature was constructed. Univariate and multivariate logistic regression analyses were applied to identify the independent clinical risk factors and construct the clinical model. Other different models, including the conventional PET model, combined PET-clinical model and combined radiomics model, were built using logistic regression. The combined radiomics model was based on clinical factors, conventional PET parameters and radiomics signature, which was presented as a radiomics nomogram. The diagnostic performance of the different models was evaluated by receiver operating characteristic (ROC) curves and decision curve analysis (DCA). RESULTS: By visual assessment, BMI was observed in 80 patients. Four conventional PET parameters (SUVmax, SUVmean, metabolic tumor volume, and total lesion glycolysis) were extracted. And 15 radiomics features were selected to build the radiomics signature. The 11q aberration, neuron-specific enolase and vanillylmandelic acid were identified as the independent clinical risk factors to establish the clinical model. The radiomics nomogram incorporating the radiomics signature, the independent clinical risk factors and SUVmean demonstrated the best diagnostic value for identifying BMI, with an area under the curve (AUC) of 0.963 and 0.931 in the training and validation cohorts, respectively. And the DCA demonstrated that the radiomics nomogram was clinically useful. CONCLUSION: The 18F-FDG PET/CT-based radiomics nomogram which incorporates radiomics signature, independent clinical risk factors and conventional PET parameters could improve the diagnostic performance for BMI of pediatric neuroblastoma without additional medical costs and radiation exposure.

8.
ACS Omega ; 7(36): 32401-32409, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36120080

RESUMO

Approximately 70% steam-assisted gravity drainage (SAGD) wellpairs have entered into the production phase in China, while due to the fluvial sedimentation environment with strong reservoir heterogeneity, only 53% of the horizontal well section develops a steam chamber. In order to massively recover the bypassed oil and expand the steam chamber along the horizontal section, downhole electrical heating was proposed, and its mechanisms of high temperature-induced rock mechanics change and influence factors are investigated in this study using laboratory experiments and electrical steam hybrid numerical simulation. It is found that the electrical heating-assisted SAGD has four key mechanisms, namely, localized temperature elevation, development of a fixed point steam chamber, localized oil gravity drainage, and petrophysical property improvement. The influence factors include the static and operational factors, in which the permeability ratio is the primary factor for choosing SAGD wellpairs, while the steam injection rate, steam chamber operational pressure, injector and producer pressure difference, adjacent SAGD steam chamber pressure differential, heater surface temperature, and electrical heating period integrally influence the incremental production performance. Through carefully modifying the parameters, the typical SAGD wellpair steam chamber could expand from 67 to 100% along the horizontal section, with an incremental oil rate of 3-5 m3/day, and the cumulative steam/oil ratio decreases from 6.67 to 4.17. The downhole electrical heating is particularly efficient in improving steam chamber conformance in heterogeneous reservoirs and also has significant potential in similar reservoirs developed by horizontal wells.

9.
Food Chem ; 401: 134156, 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36099826

RESUMO

Influences of conventional thermal and innovative non-thermal extraction methods on the physicochemical characteristics and properties of pectic polysaccharides from Choerospondias axillaris peels were investigated. Results showed that ultrasound-assisted extracted polysaccharides (UP) had a heterogeneous nature with lower molecular weight (127.7 kDa) and lower neutral sugar content (35.1%) but higher contents of protein (4.8%) and phenolic compounds (5.1%) than those of polysaccharides extracted by hot water (HP). Additionally, the monosaccharide composition results showed that glucose (77.8%) was the most abundant monosaccharide in HP, while arabinose (67.1%) was the most abundant monosaccharide in UP. The ultrasound significantly induced the degradation of polysaccharide chains but reduced the thermal degradation of phenolics. Finally, we found that UP had higher apparent viscosity, interfacial, emulsifying and antioxidant activity but lower α-glucosidase inhibition activity than those of HP. The results indicated that we could obtain polysaccharides with different functional and biological properties by using different extraction methods.

10.
Biomed Pharmacother ; 153: 113437, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36076489

RESUMO

BACKGROUND: Anxiety is a common comorbidity of cardiovascular diseases, which deteriorated cardiac function. Chaihujialonggumulitang (BFG) was reported to have antioxidant properties, alleviate myocardial ischemia injury and improve anxiety-like behavior. The Nuclear factor erythroid 2-related factor 2 (Nrf2) /heme oxygenase-1 (HO-1) pathway is the main mechanism to defend against oxidative stress, and improve cardiac function. This study was to investigate the possible mechanism of BFG in the treatment of psycho-cardiology. METHODS: AMI with comorbid anxiety rat model was established by ligation of the left anterior descending coronary artery combined with uncertain empty bottle stimulation, followed by the administration of BFG (1 mL/100 g/d by gavage) or Dimethyl fumarate (DMF, 10 mg/kg/d by intraperitoneal injection) for 6 days. Echocardiography, myocardial injury markers, H&E, and Masson staining were employed to evaluate cardiac function. Behavioral tests and hippocampus neurotransmitters were applied to record anxiety-like behavior. We employed immunohistochemistry, RT-PCR, western blotting, and biochemical analysis to detect the protein and gene expression of Nrf2/HO-1 pathway-related factors, and oxidative stress and apoptosis parameters. RESULTS: Rats in the AMI and complex groups showed cardiac function deterioration, as well as anxiety-like behavior. BFG improved echocardiography indicators, reduced myocardial injury markers, and attenuated myocardial pathological changes. BFG also ameliorated anxiety-like behaviors and elevated neurotransmitters levels. BFG promoted the activation of Nrf2/HO-1 pathway, increased antioxidant enzyme activities, reduced lipid peroxidation levels, and alleviated oxidative damage and apoptosis. DMF showed therapeutic effects and molecular mechanisms similar to BFG. CONCLUSION: BFG may possess a psycho-cardiology therapeutic effect on AMI with comorbid anxiety by the activation of the Nrf2/HO-1 pathway and suppression of oxidative stress and apoptosis.


Assuntos
Cardiologia , Infarto do Miocárdio , Animais , Antioxidantes/farmacologia , Ansiedade , Apoptose , Comorbidade , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Heme Oxigenase (Desciclizante) , Heme Oxigenase-1/metabolismo , Infarto do Miocárdio/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
11.
Artigo em Inglês | MEDLINE | ID: mdl-36114966

RESUMO

Water-based drilling cuttings (WDC) generated during shale gas development will endanger human health and ecological security. The modern analytical techniques are used to analyze the organic pollutants in WDC, and the human health and ecological security risks of harmful pollutants in WDC under specific scenarios are evaluated. The results showed that the content of organic pollutants in WDC was evaluated by human health and safety risk assessment. The comprehensive carcinogenic risks of all exposure pathways of single pollutant benzo(a)anthracene, benzo(a)pyrene, benzo(k)fluoranthene, and indeno(1,2,3-cd)pyrene were acceptable. However, the cumulative carcinogenic risk of exposure to dibenzo(a,h)anthracene particles via skin exposure was not acceptable. It was considered that only dibenzo(a,h)anthracene had carcinogenic effect, and the risk control limit of dibenzo(a,h)anthracene in WDC was 1.8700 mg/kg by calculation. As well as, the "WDC-cement" gel composite structure was deeply analyzed, and the physical and chemical properties and mechanism of organic pollutants in cement solidified WDC were analyzed, which provided theoretical support for the study of WDC pavement cushion formula. Based on the above conclusions and combined with the actual site, by studying and adjusting the formula of WDC pavement cushion, the WDC pavement cushion was finally designed by 6% cement + 50% WDC + 44% crushed stone. The 7d unconfined compressive strength met the requirements of the Chinese standard "Technical Guidelines for Construction of Highway Roadbases" (JTG/T F20-2015). Also, the process route of WDC as road cushion product was sampled and analyzed. In addition, the leaching concentration of main pollutants all met the relevant standards of China. Therefore, this study can provide a favorable way for the efficient, safe, and environmentally friendly utilization of WDC, and ensure the ecological environment safety and human health safety of WDC in resource utilization.

12.
Chin Herb Med ; 14(2): 273-282, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36117665

RESUMO

Objective: Nonalcoholic fatty liver disease (NAFLD) has become a common chronic liver disease that is harmful to human health. Moreover, there is currently no FDA-approved first-line drug for the treatment of nonalcoholic steatohepatitis (NASH) or NAFLD. Traditional Chinese medicine (TCM) is widely used to ameliorate liver diseases, such as the traditional ancient recipe called Three Flower Tea (TFT), which consists of double rose (Rosa rugosa), white chrysanthemum (Chrysanthemum morifolium), and Daidaihua (Citrus aurantium). However, the mechanisms of the action of TFT are not clear. Therefore, this study aimed to elucidate the mechanisms of TFT against NAFLD in high-fat diet (HFD)-induced rats. Methods: This study utilized bioinformatics and network pharmacology to establish the active and potential ingredient-target networks of TFT. Furthermore, a protein-protein interaction (PPI) network was constructed, and enrichment analysis was performed to determine the key targets of TFT against NAFLD. Furthermore, an animal experiment was conducted to evaluate the therapeutic effect and confirm the key targets of TFT against NAFLD. Results: A total of 576 NAFLD-related genes were searched in GeneCards, and under the screening criteria of oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18, a total of 19 active ingredients and 210 targets were identified in TFT. Network pharmacology analysis suggested that 55 matching targets in PPIs were closely associated with roles for NAFLD treatment. Through the evaluation of network topology parameters, four key central genes, PPARγ, SREBP, AKT, and RELA, were identified. Furthermore, animal experiments indicated that TFT could reduce plasma lipid profiles, hepatic lipid profiles and hepatic fat accumulation, improve liver function, suppress inflammatory factors, and reduce oxidative stress. Through immunoblotting and immunofluorescence analysis, PPARγ, SREBP, AKT, and RELA were confirmed as targets of TFT in HFD-induced rats. Conclusion: In summary, our results indicate that TFT can prevent and treat NAFLD via multiple targets, including lipid accumulation, antioxidation, insulin sensitivity, and inflammation.

13.
Light Sci Appl ; 11(1): 268, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36100587

RESUMO

Secure information retrieval is an essential task in today's highly digitised society. In some applications, it may be necessary that user query's privacy and database content's security are enforced. For these settings, symmetric private information retrieval (SPIR) could be employed, but its implementation is known to be demanding, requiring a private key-exchange network as the base layer. Here, we report for the first time a realisation of provably-secure SPIR supported by a quantum-secure key-exchange network. The SPIR scheme looks at biometric security, offering secure retrieval of 582-byte fingerprint files from a database with 800 entries. Our experimental results clearly demonstrate the feasibility of SPIR with quantum secure communications, thereby opening up new possibilities in secure distributed data storage and cloud computing over the future Quantum Internet.

14.
Front Psychol ; 13: 957426, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110272

RESUMO

Embodied cognition theory posits that concept representations inherently rely on sensorimotor experiences that accompany their acquisitions. This is well established through concrete concepts. However, it is debatable whether representations of abstract concepts are based on sensorimotor representations. This study investigated the causal role of associated motor experiences that accompany concept acquisition in the involvement of the motor system in the abstract verb processing. Through two experiments, we examined the action-sentence compatibility effect, in the test phase after an increase in motor features during the learning phase for abstract verbs with low motor features (Experiment 1) or novel words with no conceptual features at all (Experiment 2). After associated motor experiences were added in the word learning phase, action-sentence compatibility effect was found in the semantic processing tasks during the test phase for abstract verbs (Experiment 1a) and novel words (Experiment 2). This was lacking in the word font color judgment task requiring no semantic processing (Experiment 1b). Coupled with our previous study, these findings suggest that motor features formed during word learning could causally affect embodiment in the motor system for abstract verbs, and reactivation of motor experiences in abstract verb processing depends on a given task's demands. Our study supports the view that conceptual representations, even abstract concepts, can be grounded in sensorimotor experiences.

15.
J Integr Plant Biol ; 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36114789

RESUMO

Clathrin-mediated endocytosis (CME) is the major endocytic pathway in eukaryotic cells that directly regulates abundance of plasma membrane (PM) proteins. Clathrin triskelia are composed of clathrin heavy chains (CHCs) and light chains (CLCs), and the phytohormone auxin differentially regulates membrane-associated CLCs and CHCs, modulating the endocytosis and therefore the distribution of auxin efflux transporter PIN-FORMED2 (PIN2). However, the molecular mechanisms by which auxin regulates clathrin are still poorly understood. Transmembrane kinase family proteins (TMKs) are considered to contribute to auxin signaling and plant development, it remains unclear whether they are involved in PIN transport by CME. We assessed TMKs involvement in the regulation of clathrin by auxin, using genetic, pharmacological, and cytological approaches including live-cell imaging and immunofluorescence. In tmk1 mutant seedlings, auxin failed to rapidly regulate abundance of both CHC and CLC and to inhibit PIN2 endocytosis, leading to an impaired asymmetric distribution of PIN2 and therefore auxin. Furthermore, TMK3 and TMK4 were shown not involved in regulation of clathrin by auxin. In summary, TMK1 is essential for auxin-regulated clathrin recruitment and CME. TMK1 therefore plays a critical role in the establishment of an asymmetric distribution of PIN2 and an auxin gradient during root gravitropism. This article is protected by copyright. All rights reserved.

16.
Eur J Pharmacol ; : 175262, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-36100129

RESUMO

Among pulmonary arterial hypertension (PAH) patients, right ventricular (RV) functioning has been considered a major determining factor for cardiac capacity and survival. However, despite the recognition of the clinical importance for preserving RV functioning, no effective treatments are currently available for RV failure. This study aims to suggest one such possible treatment, through investigating the cardio-protective capabilities of the anti-oxidant, melatonin (Mel), for treating adverse RV remodeling in PAH, along with its underlying mechanisms. Arginine vasopressin induced neonatal rat cardiomyocyte hypertrophy in vitro; in vivo, PAH was induced in rats through intraperitoneal monocrotaline (MCT) injections, and Mel was administered intraperitoneally 24 h prior to MCT. Mel reduced rat cardiomyocyte hypertrophy and mitochondrial oxidative stress in vitro by activating the Mst1-Nrf2 pathway, which were all reversed upon siRNA knockdown of Mst1. Likewise, in vivo, Mel pre-treatment significantly ameliorated MCT-induced deterioration in cardiac function, RV hypertrophy, fibrosis and dilation. These beneficial effects were also associated with Mst1-Nrf2 pathway up regulation and its associated reduction in oxidative stress, as evidenced by the decrease in RV malondialdehyde content. Notably, results from Mel treatment were similar, or even superior, to those obtained from N-acetyl cysteine (NAC), which has already been-confirmed as an anti-oxidative treatment for PAH. By contrast, co-treatment with the Mst1 inhibitor XMU-MP-1 reversed all of those Mel-associated beneficial effects. Our findings thus identified Mel as a potent cardio-protective agent against the onset of maladaptive RV remodeling, through enhancement of the anti-oxidative response via Mst1-Nrf2 pathway activation.

17.
Immunity ; 55(9): 1663-1679.e6, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36070768

RESUMO

Interleukin-23 receptor plays a critical role in inducing inflammation and autoimmunity. Here, we report that Th1-like cells differentiated in vitro with IL-12 + IL-21 showed similar IL-23R expression to that of pathogenic Th17 cells using eGFP reporter mice. Fate mapping established that these cells did not transition through a Th17 cell state prior to becoming Th1-like cells, and we observed their emergence in vivo in the T cell adoptive transfer colitis model. Using IL-23R-deficient Th1-like cells, we demonstrated that IL-23R was required for the development of a highly colitogenic phenotype. Single-cell RNA sequencing analysis of intestinal T cells identified IL-23R-dependent genes in Th1-like cells that differed from those expressed in Th17 cells. The perturbation of one of these regulators (CD160) in Th1-like cells inhibited the induction of colitis. We thus uncouple IL-23R as a purely Th17 cell-specific factor and implicate IL-23R signaling as a pathogenic driver in Th1-like cells inducing tissue inflammation.


Assuntos
Colite , Receptores de Interleucina , Animais , Inflamação/metabolismo , Interleucina-23/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fenótipo , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Células Th1 , Células Th17
18.
J Org Chem ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36106472

RESUMO

Chiral O-N-N tridentate ligands were designed from proline and BINOL. Their design strategy and performance were evaluated using a copper(II)-catalyzed asymmetric Henry reaction as a model. The desired ß-nitroalcohols were obtained in up to 94% ee's. Preliminary results suggested that the stereofacial selection of the reactions was mainly controlled by the chiral diamine moiety derived from proline, and matching of the central and axial chiralities was essential for the high stereoselectivity of the reaction. Enantioswitching was observed when an appropriate substituent was introduced to the binaphthyl group. Si-selections were found in reactions using 2a without 3-substituents as chiral ligand, and Re-selections were found with the same high enantioselectivities when 2i bearing the 3-trifluoromethyl group was used as the chiral ligand.

19.
ACS Appl Mater Interfaces ; 14(36): 41421-41432, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36049051

RESUMO

With the advancement of material science and electronic technology, wearable devices have been integrated into daily lives, no longer just a stirring idea in science fiction. In the future, robust multifunctionalized wearable devices with low cost and long-term service life are urgently required. However, preparing multifunctional wearable devices robust enough to resist harsh conditions using a commercially available raw material through a simple process still remains challenging. In this work, reprocessable polyurea (HUBTPU) with a hard segment of hindered urea bonds (HUBs) and a soft segment of polyether is synthesized via a facile one-pot method. The robust dual functional wearable devices were obtained by simply spray-coating silver nanowires (AgNWs) on HUBTPU elastomer substrates. Due to the dynamic combination and decomposition of the HUBs and hydrogen bonds at 130 °C, the robust elastomer demonstrates favorable adhesion to various substrates. Especially, the partially embedded AgNW structure is also achieved by using ethanol as a spray solvent. The adhesion of HUBTPU substrates and embedded structure leads to stronger interfacial adhesion and stability compared to non-adhesive substrates. The as-obtained HUBTPU electrodes are able to be heated to 115 °C by applying a low voltage and sensing the strain deformation caused by human movement, which means that the electrodes are endowed with both electrical heating capability and strain sensing functionality. Therefore, this strategy reveals a potential way to prepare multifunctional wearable devices using other conductive particles and adhesive functional polymer substrates.

20.
Biomed Pharmacother ; 154: 113622, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36081291

RESUMO

Osteoclasts play an important role in maintaining the relative stability of bone mass. Abnormal number and function of osteoclasts are closely related to osteoporosis and osteolytic diseases. Thiaplakortone B (TPB), a natural compound derived from the Great Barrier Reef sponge Plakortis lita, has been reported to inhibit the growth of the malaria parasite, Plasmodium falciparum, but its effect on osteoclastogenesis has not been previously investigated. In our study, we found that TPB suppresses the receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclast formation and resorption activity by tartrate-resistant acid phosphatase (TRAcP) staining, immunofluorescence staining of F-actin belts and hydroxyapatite resorption assay. Furthermore, using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analysis, we discovered that TPB inhibits osteoclast-specific genes and proteins expression. Mechanistically, TPB blocks multiple upstream pathways including calcium oscillation, NF-κB, mitogen-activated protein kinase (MAPK) and nuclear factor of activated T cells 1(NFATc1) signaling pathways. In vivo, TPB could dampen bone loss in an ovariectomy (OVX) mouse model by micro-CT assessment and histological staining. Therefore, TPB may serve as a potential therapeutic candidate for the treatment of osteoporosis and osteolysis.


Assuntos
NF-kappa B , Osteoporose , Animais , Sinalização do Cálcio , Diferenciação Celular , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Osteoclastos , Osteogênese , Osteoporose/patologia , Ovariectomia , Ligante RANK/metabolismo
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