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1.
Plant Physiol ; 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39133896

RESUMO

Hydrogen sulphide (H2S) is required for optimal establishment of soybean (Glycine max)-Sinorhizobium fredii symbiotic interaction, yet its role in regulating the nitrogen fixation-senescence transition remains poorly understood. A S. fredii cystathionine γ-lyase (CSE) mutant deficient in H2S synthesis showed early nodule senescence characterized by reduced nitrogenase activity, structural changes in nodule cells, and accelerated bacteroid death. In parallel, the CSE mutant facilitated the generation of reactive oxygen species (ROS) and elicited antioxidant responses. We observed that H2S-mediated persulfidation of cysteine C31/C80 in ascorbate peroxidase (APX) and C32 in APX2 modulated enzyme activity, thereby participating in hydrogen peroxide (H2O2) detoxification and delaying nodule senescence. Comparative transcriptomic analysis revealed a significant up-regulation of GmMYB128, an MYB transcription factor (TF), in the CSE mutant nodules. Functional analysis through overexpression and RNAi lines of GmMYB128 demonstrated its role as a positive regulator in nodule senescence. MYB128-OE inoculated with the CSE mutant strain exhibited a reduction in nitrogenase activity and a significant increase in DD15 expression, both of which were mitigated by NaHS addition. Changes at the protein level encompassed the activation of plant defenses alongside turnover in carbohydrates and amino acids. Our results suggest that H2S plays an important role in maintaining efficient symbiosis and preventing premature senescence of soybean nodules.

2.
Sensors (Basel) ; 24(14)2024 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-39065953

RESUMO

Pavement condition monitoring is an important task in road asset management and efficient abnormal pavement condition detection is critical for timely conservation management decisions. The present work introduces a mobile pavement condition monitoring approach utilizing low-cost sensor technology and machine-learning-based methodologies. Specifically, an on-board unit (OBU) embedded with an inertial measurement unit (IMU) and global positioning system (GPS) is applied to collect vehicle posture data in real time. Through a comprehensive analysis of both time domain and frequency domain data features for both normal and abnormal pavement conditions, feature engineering is conducted to identify how the most important features affect abnormal pavement condition recognition. Six machine learning models are then developed to identify different types of pavement conditions. The performance of different algorithms and the significance of different features are then analyzed. Moreover, the influence of vehicle speed on pavement condition assessment is further examined and classification models for different speed intervals are developed. The results indicate that the random forest (RF) model that considers vehicle speed achieves the best performance in pavement condition monitoring. The outcomes of the present work would contribute to cost-effective pavement condition monitoring and provide an important reference for pavement maintenance sectors.

3.
Plant Cell Environ ; 46(8): 2523-2541, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37303272

RESUMO

Hydrogen sulfide (H2 S) performs a crucial role in plant development and abiotic stress responses by interacting with other signalling molecules. However, the synergistic involvement of H2 S and rhizobia in photosynthetic carbon (C) metabolism in soybean (Glycine max) under nitrogen (N) deficiency has been largely overlooked. Therefore, we scrutinised how H2 S drives photosynthetic C fixation, utilisation, and accumulation in soybean-rhizobia symbiotic systems. When soybeans encountered N deficiency, organ growth, grain output, and nodule N-fixation performance were considerably improved owing to H2 S and rhizobia. Furthermore, H2 S collaborated with rhizobia to actively govern assimilation product generation and transport, modulating C allocation, utilisation, and accumulation. Additionally, H2 S and rhizobia profoundly affected critical enzyme activities and coding gene expressions implicated in C fixation, transport, and metabolism. Furthermore, we observed substantial effects of H2 S and rhizobia on primary metabolism and C-N coupled metabolic networks in essential organs via C metabolic regulation. Consequently, H2 S synergy with rhizobia inspired complex primary metabolism and C-N coupled metabolic pathways by directing the expression of key enzymes and related coding genes involved in C metabolism, stimulating effective C fixation, transport, and distribution, and ultimately improving N fixation, growth, and grain yield in soybeans.


Assuntos
Glycine max , Rhizobium , Glycine max/genética , Rhizobium/fisiologia , Fixação de Nitrogênio/fisiologia , Nitrogênio/metabolismo , Fotossíntese , Simbiose/genética
4.
Br J Dermatol ; 189(6): 666-673, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37708254

RESUMO

BACKGROUND: Baricitinib is approved for the treatment of adults with severe alopecia areata (AA). In the absence of robust data on the patterns of regrowth during treatment of severe AA, there is a gap in the knowledge regarding treatment expectations. OBJECTIVES: To examine whether different clinical response subgroups could be identified in baricitinib-treated patients with severe AA and factors that contribute to these subgroups. METHODS: The BRAVE-AA1 and BRAVE-AA2 phase III trials enrolled patients with severe AA [Severity of Alopecia Tool (SALT) score ≥ 50 (≥ 50% scalp hair loss)]. Patients randomized to baricitinib 4 mg or 2 mg retained their treatment allocation for 52 weeks. Based on patterns identified through growth mixture modelling (GMM), patients were categorized into responder subgroups according to when they first achieved ≥ 30% improvement from baseline in SALT score (SALT30). For each responder subgroup, trajectories of response (i.e. achievement of a SALT score ≤ 20, SALT score ≤ 10 and ≥ 50% change from baseline in SALT score) and baseline disease characteristics are reported. RESULTS: Respectively, 515 and 340 patients were randomized to once-daily baricitinib 4 mg and 2 mg at baseline; 69% and 51%, respectively, achieved SALT30 at least once by week 52. Based on GMM findings, we identified three responder subgroups: early (SALT30 by week 12), gradual (SALT30 after week 12-week 36) and late (SALT30 after week 36-week 52). The proportions of early, gradual and late responders and nonresponders were, respectively, 33%, 28%, 8% and 31% among patients treated with baricitinib 4 mg, and 20%, 23%, 9% and 49%, respectively, among those treated with baricitinib 2 mg. Early responders had a shorter trajectory to maximal clinical outcomes (e.g. > 78% achieved a SALT score ≤ 20 by week 36) vs. gradual or late responders. Early responders were more frequent among patients with baseline severe AA (SALT score 50 to < 95) vs. very severe AA (SALT score 95-100). Overall, responders (early to late) were more frequent in patients with short (< 4 years) episodes of hair loss. CONCLUSIONS: These analyses identified early, gradual and late responder subgroups for scalp hair regrowth in baricitinib-treated patients with severe AA, and that these subgroups are influenced by baseline characteristics. Findings from these analyses will help to inform treatment expectations for scalp hair regrowth.


Assuntos
Alopecia em Áreas , Azetidinas , Purinas , Pirazóis , Sulfonamidas , Adulto , Humanos , Alopecia em Áreas/tratamento farmacológico , Cabelo , Couro Cabeludo , Ensaios Clínicos Controlados Aleatórios como Assunto , Ensaios Clínicos Fase III como Assunto
5.
Org Biomol Chem ; 21(33): 6715-6718, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37462425

RESUMO

Using CF3SO2Na as the CF3 radical source, an eco-friendly approach for electrochemistry-mediated radical cascade cyclization of N-methacryloyl-2-phenylbenzoimidazoles was described. This reaction features mild reaction conditions, readily available substrates, and moderate to good yields through the construction of two C-C bonds in one step.

6.
J Clin Nurs ; 32(21-22): 7751-7764, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37706353

RESUMO

AIM: To examine the multidimensional properties of caregiver burden among family caregivers of patients with advanced cancer in a palliative context. DESIGN: A sequential, explanatory, mixed-method study was performed. METHODS: Family caregivers of patients diagnosed with advanced cancer were recruited from a palliative care department of a third-level hospital in Sichuan Province, China. The Caregiver Burden Inventory, Social Support Rating Scale and Connor-Davidson Resilience Scale were used to collect quantitative data, and a total of 150 caregivers were recruited from January 2022 to September 2022. Qualitative data were collected through semi-structured interviews, and a total of 22 caregivers were interviewed from October 2022 to November 2022. Survey data were analysed using descriptive statistics, and the factors of caregiver burden were identified using the Mann-Whitney U test, Kruskal-Wallis H test and Spearman correlations. Interpretative phenomenological analysis was performed to analyse the interview data to initially explore the multidimensions of caregiver burden. The following-a-thread method and convergence coding matrix were used for triangulation to examine the multidimensional properties of caregiver burden. RESULTS: The participants experienced a moderate level of caregiver burden (32.97 ± 13.09). Through triangulation, six meta-themes and nine meta-subthemes were identified as multidimensional properties of caregiver burden, including physical (too many caring tasks and poor health condition), emotional (strong negative emotions resulting from patients' suffering and insufficient and ineffective family communication), social (less social interaction and social role conflict) and economic burdens, factors that aggravate burden (prevention and control of COVID-19 and spousal relationship with patients) and factors that mitigate burden (social support). CONCLUSION: Multiple dimensions of caregiver burden were experienced by family caregivers of patients with advanced cancer in the palliative context. Family-centred palliative care must be further developed. IMPLICATIONS FOR THE PROFESSION: It is important to develop family-centred palliative care. Therefore, the focus must be on developing a rational understanding of palliative care in public and a culture-oriented death education in palliative units. IMPACT: This study adopted a mixed-method approach to comprehensively understand the phenomenon of and factors in caregiver burden in the Chinese palliative oncology context. Our findings suggest that family caregivers in palliative oncology experience a moderate level of caregiver burden, with dimensions including physical, emotional, social and economic burdens, among which emotional burden is the most prominent. The findings of this study provide policy makers and nurse practitioners with targets to be addressed in family-centred care in Chinese palliative units. REPORTING METHOD: The results of this study are reported based on the guidelines of the Mixed-Methods Article Reporting Standards. PATIENT OR PUBLIC CONTRIBUTION: Eligible caregivers were invited to participate in the study and semi-structured interviews. Nurse managers of the palliative unit helped us access the patient-management system.

7.
Worldviews Evid Based Nurs ; 20(6): 582-592, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37194163

RESUMO

BACKGROUND: Current studies have revealed that acceptance and commitment therapy (ACT) can alleviate the adverse effects of cancer; however, its effectiveness on the psychological flexibility, fatigue, sleep disturbance, and quality of life of patients with cancer remains unclear. AIMS: The aims of this study were to identify the effectiveness of ACT on psychological flexibility, fatigue, sleep disturbance, and quality of life of patients with cancer, and to explore moderators. METHODS: PubMed, Embase, Web of Science, CENTRAL, PsycINFO, CINAHL, CNKI, VIP, and Wanfang electronic databases were searched from inception to September 29, 2022. The Cochrane Collaboration's risk-of-bias assessment tool II and the Grading of Recommendations Assessment, Development, and Evaluation approach were used to evaluate evidence certainty. The data were analyzed using R Studio. The study protocol was registered with PROSPERO (CRD42022361185). RESULTS: The study included 19 relevant studies (1643 patients) published between 2012 and 2022. The pooled results showed that ACT significantly improved psychological flexibility (mean difference [MD] = -4.22, 95% CI [-7.86, -0.58], p = .02) and quality of life (Hedges' g = 0.94, 95% CI [0.59, 1.29], Z = 5.31, p < .01) but did not significantly improve fatigue (Hedges' g = -0.03, 95% CI [-0.24, 0.18], p = .75) or sleep disturbance (Hedges' g = -0.26, 95% CI [-0.82, 0.30], p = .37) in patients with cancer. Additional analyses revealed a 3-month sustainable effect on psychological flexibility (MD = -4.36, 95% CI [-8.67, -0.05], p < .05), and moderation analysis showed that intervention duration (ß = -1.39, p < .01) and age (ß = 0.15, p = .04) moderated the effects of ACT on psychological flexibility and sleep disturbance, respectively. LINKING EVIDENCE TO ACTION: Acceptance and commitment therapy demonstrates effectiveness for psychological flexibility and quality of life of patients with cancer, but there is a lack of evidence regarding its effects on fatigue and sleep disturbance. In clinical practice, ACT should be designed in more detail and rounded to achieve better results.


Assuntos
Terapia de Aceitação e Compromisso , Neoplasias , Transtornos do Sono-Vigília , Humanos , Depressão/terapia , Fadiga/etiologia , Fadiga/terapia , Neoplasias/complicações , Neoplasias/terapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Sono , Transtornos do Sono-Vigília/terapia
8.
Org Biomol Chem ; 20(47): 9362-9367, 2022 12 07.
Artigo em Inglês | MEDLINE | ID: mdl-36383151

RESUMO

A simple protocol of metal-free C-H trifluoromethylation of hydrazones via electrolysis was developed. This environment-friendly transformation showed high efficiency, good tolerance, and scaled-up functionalization, providing the desired products in moderate to good yields. At the same time, a high yield can be obtained for the substrates either bearing an electron-donating group or an electron-withdrawing group by using different trifluoromethyl reagents. In addition, the radical mechanism was confirmed by the control experiment.


Assuntos
Aldeídos , Hidrazonas
9.
Int J Med Sci ; 19(3): 537-545, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370470

RESUMO

Background: Kartogenin is a heterocyclic compound able to promote the proliferation, migration, and differentiation of various cell types and induce cartilage-like tissue regeneration. However, the role of kartogenin in hair follicles (HFs), remains unknown. We therefore investigated the effects of kartogenin on the regulation of hair growth and hair growth cycle transition. Methods: The effects of kartogenin on the proliferation, cell cycle status, and migration of primary human outer root sheath cells (ORSCs) were evaluated by MTS assay, flow cytometry, Transwell® and scratch assays, respectively. We exposed ORSCs to kartogenin (1 µM) and determined changes in mRNA and protein levels of transforming growth factor (TGF)-ß2/Smad signaling molecules by reverse transcription polymerase chain reaction, western blotting, and immunofluorescence. We also examined the effects of kartogenin (10 µM) on HFs in mice by histology following cutaneous injection. Results: Kartogenin enhanced ORSC proliferation and migration function in a dose-dependent manner, and downregulated the expression of TGF-ß2/Smad signaling molecules in vitro. Injection of kartogenin delayed catagen phase and increased regenerated hair length in mice in vivo. Conclusions: Kartogenin modulates HF growth and regulates the hair cycle and the TGF-ß2/Smad signaling pathway, providing a potential new approach for the treatment of hair loss.


Assuntos
Folículo Piloso , Ácidos Ftálicos , Alopecia , Anilidas/metabolismo , Anilidas/farmacologia , Animais , Camundongos , Ácidos Ftálicos/metabolismo , Ácidos Ftálicos/farmacologia
10.
BMC Cancer ; 21(1): 420, 2021 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863315

RESUMO

BACKGROUND: Previous studies reported cutaneous melanoma in head and neck (HNM) differed from those in other regions (body melanoma, BM). Individualized tools to predict the survival of patients with HNM or BM remain insufficient. We aimed at comparing the characteristics of HNM and BM, developing and validating nomograms for predicting the survival of patients with HNM or BM. METHODS: The information of patients with HNM or BM from 2004 to 2015 was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. The HNM group and BM group were randomly divided into training and validation cohorts. We used the Kaplan-Meier method and multivariate Cox models to identify independent prognostic factors. Nomograms were developed via the rms and dynnom packages, and were measured by the concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic (ROC) curve and calibration plots. RESULTS: Of 70,605 patients acquired, 21% had HNM and 79% had BM. The HNM group contained more older patients, male sex and lentigo maligna melanoma, and more frequently had thicker tumors and metastases than the BM group. The 5-year cancer-specific survival (CSS) and overall survival (OS) rates were 88.1 ± 0.3% and 74.4 ± 0.4% in the HNM group and 92.5 ± 0.1% and 85.8 ± 0.2% in the BM group, respectively. Eight variables (age, sex, histology, thickness, ulceration, stage, metastases, and surgery) were identified to construct nomograms of CSS and OS for patients with HNM or BM. Additionally, four dynamic nomograms were available on web. The internal and external validation of each nomogram showed high C-index values (0.785-0.896) and AUC values (0.81-0.925), and the calibration plots showed great consistency. CONCLUSIONS: The characteristics of HNM and BM are heterogeneous. We constructed and validated four nomograms for predicting the 3-, 5- and 10-year CSS and OS probabilities of patients with HNM or BM. These nomograms can serve as practical clinical tools for survival prediction and individual health management.


Assuntos
Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Melanoma/mortalidade , Melanoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Melanoma/epidemiologia , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Nomogramas , Especificidade de Órgãos , Vigilância da População , Prognóstico , Modelos de Riscos Proporcionais , Curva ROC , Reprodutibilidade dos Testes , Programa de SEER
11.
J Org Chem ; 86(17): 12257-12266, 2021 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-34387487

RESUMO

We report an efficient iron-catalyzed cross-dehydrogenative coupling [4 + 2] annulation of secondary/tertiary anilines with quinazolinones to generate quinoline-spiroquinzolinones. The reaction proceeds smoothly with a relatively broad variety of functional groups, a cheap transition metal catalyst (FeCl3), and environmentally friendly oxidant (H2O2/O2) under mild reaction conditions. Creatively, N-methylanilines are employed for the first time for the cycloaddition as both methyl and methylene sources attached to the N atom of tetrahydroquinolines.


Assuntos
Compostos de Anilina , Quinolinas , Catálise , Reação de Cicloadição , Peróxido de Hidrogênio , Ferro , Quinazolinonas
12.
J Org Chem ; 86(1): 310-321, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33332126

RESUMO

A simple and practical domino protocol for the selective synthesis of 2-aroylbenzothiazoles and 2-aryl benzothiazoles catalyzed by I2 is developed under metal-free conditions. The reaction outcomes are exclusively controlled by the reaction oxidant/medium. With DMSO employed as both the solvent and the oxidant, an oxidation of aromatic methyl ketones takes precedence over the condensation with 2-aminobenzenethiols. On the other hand, when the reaction was carried out in PhNO2 or in 1,4-dioxane containing PhNO2, the condensation of aromatic methyl ketones with 2-aminobenzenethiols has priority to form imines which is followed by an oxidation of the methyl group from ketones to afford 2-arylbenzothiazoles as a sole product. The PhNO2/I2 co-catalytic system is proposed first time.

13.
J Org Chem ; 86(5): 3897-3906, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33595303

RESUMO

A one-pot, four-component annulation of 2,3,4,6-tetraarylpyridines from aromatic aldehydes, methyl ketones, diaryl ethanones, and ammonium acetate is described. The reaction features high functional group compatibility in air under solvent-free conditions without any additive and only water as the nontoxic byproduct, providing a strategy for the facile, economical, and eco-friendly construction of multiaryl-substituted pyridines from simple and readily available reactants.


Assuntos
Aldeídos , Piridinas
14.
J Org Chem ; 86(2): 1448-1455, 2021 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-33373228

RESUMO

A novel procedure for a one-pot cascade reaction of o-aminoacetophenones and aryl/aliphatic isocyanates catalyzed/oxidized by the [Pd]/[Ag] system was developed. The reaction involves two C-N bond and one C-C bond formations during the double annulation process and the desired indoloquinazolinones and derivatives were afforded up to 81% yields from readily available substrates with a tolerance of a broad variety.

15.
Anal Bioanal Chem ; 413(21): 5409-5417, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34235569

RESUMO

In this study, a novel kind of imprinted polymers based on metal-organic frameworks (MOF@DES-MIPs) was prepared, using bovine hemoglobin (BHb) as template molecules and deep eutectic solvents (DES) as functional monomers for selective recognition and adsorption of BHb. MOF were used as the substrates to improve the accessibility of imprinted sites and DES as the functional monomers to produce different forces for BHb to help the formation of imprinted sites. Imprinted polymer films were taken to provide analyte selectivity. The MOF@DES-MIPs prepared were characterized and evaluated by scanning electron microscope, X-ray diffraction, and Fourier transform infrared spectrometer. We also investigated the influences of BHb concentration and adsorption time on the performance of MOF@DES-MIPs. The maximal adsorption capacity of MOF@DES-MIPs to BHb reached 151.28 mg g-1, and the MOF@DES-MIPs showed good selectivity and fast adsorption equilibrium, which might offer a novel method for the preparation and research of molecularly imprinted polymers of biomacromolecules. In addition, MOF@DES-MIPs were successfully applied in the selective recognition of BHb from a real bovine blood sample. Graphical abstract.


Assuntos
Hemoglobinas/isolamento & purificação , Estruturas Metalorgânicas/química , Polímeros Molecularmente Impressos/química , Adsorção , Animais , Bovinos , Impressão Molecular , Solventes
16.
Int J Med Sci ; 18(15): 3498-3505, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522176

RESUMO

Sox transcription factors play many diverse roles during development, including regulating stem cell states, directing differentiation, and influencing the local chromatin landscape. Sox10 has been implicated in the control of stem/progenitor activity and epithelial-mesenchymal transition, yet it has not been studied in relation to the hair follicle cycle or hair follicle stem cell (HFSC) control. To elucidate the role of Sox10 in hair follicle cycle control, we performed immunohistochemical and immunofluorescence analysis of its expression during hair morphogenesis, the postnatal hair cycle, and the depilation-induced murine hair follicle cycle. During hair follicle morphogenesis, Sox10 was expressed in the hair germ and peg. In telogen, we detected nuclear Sox10 in the hair bulge and germ cell cap, where HFSCs reside, while in anagen and catagen, Sox10 was detected in the epithelial portion, such as the strands of keratinocytes, the outer root sheath (ORS) in anagen, and the regressed epithelial strand of hair follicle in catagen. These results suggest that Sox10 may be involved in early hair follicle morphogenesis and postnatal follicular cycling.


Assuntos
Expressão Gênica/genética , Folículo Piloso/crescimento & desenvolvimento , Queratinócitos/citologia , Fatores de Transcrição SOXE/genética , Células-Tronco/citologia , Animais , Ciclo Celular/genética , Diferenciação Celular/genética , Camundongos , Morfogênese/genética
17.
Stat Med ; 39(7): 845-874, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-31912927

RESUMO

Safety of medical products presents a serious concern worldwide. Surveillance systems of postmarket medical products have been established for continual monitoring of adverse events (AEs) in many countries, and the proliferation of electronic health record systems further facilitates continual monitoring for AEs. We review existing statistical methods for signal detection that are mostly in use in postmarketing safety surveillance of spontaneously reported AEs and we study their performance characteristics by simulation. We compare those with the likelihood ratio test (LRT) method (appropriately modified for use in pharmacovigilance) and use three different methods to generate data (AE based, drug based, and a modification of the method of Ahmed et al). Performance metrics include type I error, power, sensitivity, and false discovery rate, among others. The results show superior performance of the LRT method in almost all simulation experiments. An application to the FDA Adverse Event Reporting System database is illustrated using rhabdomyolysis-related preferred terms reported to FDA during the third-quarter of 2014 to the first-quarter of 2017 for statin drugs. We present a critical discussion and recommendations for use of these methods.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Bases de Dados Factuais , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos , Funções Verossimilhança , Farmacovigilância , Vigilância de Produtos Comercializados
18.
J Neuroinflammation ; 15(1): 2, 2018 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-29301581

RESUMO

BACKGROUND: Inflammasomes are involved in diverse inflammatory diseases. Previous study reported that the neurotransmitter dopamine inhibited NLRP3 inflammasome activation via dopamine D1 receptor (DRD1). The present study aims to investigate the role of DRD1 on neuroinflammation in intracerebral hemorrhage (ICH) mice and the potential mechanism mediated by NLRP3 inhibition. METHODS: One hundred and six male CD-1 mice were subjected to intrastriatal injection of bacterial collagenase or PBS. A68930 (DRD1 specific agonist) was administered by subcutaneous injection at 1 h after collagenase injection. Behavioral deficits and brain water content were assayed. The expression of Iba 1 and MPO levels were measured by immunofluorescence staining. The expressions of proteins in the DRD1/interferon-beta (IFN-beta)/NLRP3 signaling pathway were evaluated by western blotting. RESULTS: Activation of the DRD1 by A68930 decreased brain edema and improved behavior at 24 and 72 h of ICH. A68930 inhibited partly the activation of microglia and the neutrophil infiltration after 24 h of ICH. IFN-beta, p-STAT1 increased while NLRP3, caspase 1, and IL-1beta decreased after A68930 administration in ICH mice. DRD1 antagonist and IFN-beta siRNA reversed effects of A68930 on neurological outcome and brain edema. DRD1 antagonist and IFN-beta siRNA blocked not only A68930-mediated increases of IFN-beta, p-STAT1 but also A68930-mediated decreases of NLRP3, caspase 1, and IL-1beta. CONCLUSIONS: DRD1 activation by A68930 improves neurological outcome through inhibition of NLRP3-mediated inflammation in ICH mice.


Assuntos
Edema Encefálico/metabolismo , Hemorragia Cerebral/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/metabolismo , Animais , Edema Encefálico/prevenção & controle , Hemorragia Cerebral/prevenção & controle , Agonistas de Dopamina/farmacologia , Agonistas de Dopamina/uso terapêutico , Antagonistas de Dopamina/farmacologia , Masculino , Camundongos , RNA Interferente Pequeno/farmacologia , Distribuição Aleatória , Receptores de Dopamina D1/antagonistas & inibidores
19.
Molecules ; 23(5)2018 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-29783643

RESUMO

Lipopolysaccharide (LPS)-induced neuroinflammation triggers and accelerates the pathogenesis of Parkinson's disease (PD). Carthamus tinctorius L., a traditional Chinese medicine, has been widely used for the treatment of cerebrovascular disease. Hydroxysafflor Yellow A (HSYA) is an active component of C. tinctorius. The purpose of this study was to investigate whether HSYA could attenuate LPS-induced neurotoxicity and neuroinflammation in primary mesencephalic cultures. Cell viability was measured by MTT and LDH assays. The number of tyrosine hydroxylase (TH) positive neuron was observed by immunohistochemistry. NF-κB p65 and iNOS expressions were evaluated with western blotting method. Pro-inflammatory cytokines including IL-1ß and TNF-α were determined by ELISA kits. Nitric oxide (NO) content in the culture medium was assayed. The results showed that HSYA treatment significantly attenuated the LPS-induced dopaminergic neurons damage. HSYA partially inhibited the expressions of NF-κB p65 and iNOS. Furthermore, HSYA decreased the content of IL-1ß, TNF-α and NO in the supernatants. Taken together, these results suggest that HSYA exerts protective effects on LPS-induced neurotoxicity in dopaminergic neurons and the mechanisms may be associated with the inhibition of inflammatory response.


Assuntos
Chalcona/análogos & derivados , Inflamação/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Neurônios/efeitos dos fármacos , Quinonas/farmacologia , Animais , Carthamus tinctorius/química , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Chalcona/química , Chalcona/farmacologia , Citocinas/metabolismo , Humanos , Mesencéfalo/citologia , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Óxidos de Nitrogênio , Cultura Primária de Células , Quinonas/química , Transdução de Sinais , Distribuição Tecidual , Fator de Transcrição RelA/metabolismo
20.
J Sep Sci ; 40(3): 733-743, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27888568

RESUMO

A new multiple monolithic fiber solid-phase microextraction using a polydopamine-based monolith as the extraction medium is proposed. The monolith was synthesized by facile in situ copolymerization of N-methacryldopamine and dual cross-linkers (divinylbenzene/ethylenedimethacrylate) in the presence of N,N-dimethylformamide. The effect of the contents of N-methacryldopamine and porogen in the polymerization mixture on the extraction performance was investigated thoroughly. A series of characterization studies was performed to validate the structure and properties of the monolith. The prepared multiple monolithic fibers were used for the extraction of triazine herbicides in environmental water samples. After the optimization of the extraction parameters, a convenient, sensitive, cost-effective, and environmentally friendly method for the determination of trace triazine herbicides in water samples was developed by coupling multiple monolithic fibers solid-phase microextraction with high-performance liquid chromatography and diode array detection. The results indicated that the limits of detection and quantification for the target compounds were 0.031-0.14 and 0.10-0.45 µg/L, respectively. Good precision and reproducibility were obtained with the relative standard deviations below 10%. The developed method was applied to the analysis of the triazine herbicides in different water samples (lake, river, and farmland waters). The recoveries of the method were in the range between 79.6 and 117%.

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