Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 47
Filtrar
1.
Psychiatry Res ; 335: 115886, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38574699

RESUMO

We aim to systematically review and meta-analyze the effectiveness and safety of psychedelics [psilocybin, ayahuasca (active component DMT), LSD and MDMA] in treating symptoms of various mental disorders. Web of Science, Embase, EBSCO, and PubMed were searched up to February 2024 and 126 articles were finally included. Results showed that psilocybin has the largest number of articles on treating mood disorders (N = 28), followed by ayahuasca (N = 7) and LSD (N = 6). Overall, psychedelics have therapeutic effects on mental disorders such as depression and anxiety. Specifically, psilocybin (Hedges' g = -1.49, 95% CI [-1.67, -1.30]) showed the strongest therapeutic effect among four psychedelics, followed by ayahuasca (Hedges' g = -1.34, 95% CI [-1.86, -0.82]), MDMA (Hedges' g = -0.83, 95% CI [-1.33, -0.32]), and LSD (Hedges' g = -0.65, 95% CI [-1.03, -0.27]). A small amount of evidence also supports psychedelics improving tobacco addiction, eating disorders, sleep disorders, borderline personality disorder, obsessive-compulsive disorder, and body dysmorphic disorder. The most common adverse event with psychedelics was headache. Nearly a third of the articles reported that no participants reported lasting adverse effects. Our analyses suggest that psychedelics reduce negative mood, and have potential efficacy in other mental disorders, such as substance-use disorders and PTSD.


Assuntos
Alucinógenos , Transtornos Mentais , N-Metil-3,4-Metilenodioxianfetamina , Transtorno Obsessivo-Compulsivo , Humanos , Alucinógenos/efeitos adversos , Psilocibina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/uso terapêutico , Dietilamida do Ácido Lisérgico/efeitos adversos , Transtornos Mentais/tratamento farmacológico , Transtornos Mentais/induzido quimicamente , Transtorno Obsessivo-Compulsivo/tratamento farmacológico
2.
Food Funct ; 15(8): 4292-4309, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38526853

RESUMO

Asthma is a chronic inflammatory disorder in airways with typical pathologic features of airway inflammation and mucus hypersecretion. α-Terpineol is a monocyclic terpene found in many natural plants and foods. It has been reported to possess a wide range of pharmacological activities including anti-inflammatory and expectorant effects. However, the role of α-terpineol in asthma and its potential protective mechanism have not been well elucidated. This study is designed to investigate the pharmacological effect and mechanism of α-terpineol on asthmatic mice using the metabolomics platform. A murine model of asthma was established using ovalbumin (OVA) sensitization and then challenged for one week. The leukocyte count and inflammatory cytokines in the bronchoalveolar lavage fluid (BALF), lung histopathology, inflammatory  infiltrate and mucus secretion were evaluated. An ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based metabolomics study was performed on lung tissues and serum to explore endogenous small molecule metabolites affected by α-terpineol in asthmatic mice. After α-terpineol treatment, leukocyte count, inflammatory cytokines in the BALF, and peribronchial inflammation infiltration were significantly downregulated. Goblet cell hyperplasia and mucus secretion were attenuated, with the level of Muc5ac in BALF decreased. These results proved the protective effect of α-terpineol against airway inflammation, mucus hypersecretion and Th1/Th2 immune imbalance. To further investigate the underlying mechanisms of α-terpineol in asthma treatment, UPLC-MS/MS-based metabolomics analysis was performed. 26 and 15 identified significant differential metabolites were found in the lung tissues and serum of the control, model and α-terpineol groups, respectively. Based on the above differential metabolites, enrichment analysis showed that arachidonic acid (AA) metabolism was reprogrammed in both mouse lung tissues and serum. 5-Lipoxygenase (5-LOX) and cysteinyl leukotrienes (CysLTs) are the key enzyme and the end product of AA metabolism, respectively. In-depth studies have shown that pretreatment with α-terpineol can alleviate asthma by decreasing the AA level, downregulating the expression of 5-LOX and reducing the accumulation of CysLTs in mouse lung tissues. In summary, this study demonstrates that α-terpineol is a potential agent that can prevent asthma via regulating disordered AA metabolism.


Assuntos
Ácido Araquidônico , Asma , Líquido da Lavagem Broncoalveolar , Monoterpenos Cicloexânicos , Pulmão , Metabolômica , Camundongos Endogâmicos BALB C , Animais , Asma/tratamento farmacológico , Asma/metabolismo , Camundongos , Monoterpenos Cicloexânicos/farmacologia , Ácido Araquidônico/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Feminino , Modelos Animais de Doenças , Citocinas/metabolismo , Ovalbumina , Espectrometria de Massas em Tandem , Mucina-5AC/metabolismo , Cromatografia Líquida de Alta Pressão
3.
Environ Geochem Health ; 46(4): 127, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38483668

RESUMO

Dissolved oxygen is one of the important comprehensive indicators of river water quality, which reflects the degree of pollution in the water body. Monitoring and predicting dissolved oxygen are an important tool for water quality management, which helps to effectively maintain water ecological balance and prevent environmental problems. A single model cannot describe the dynamic characteristics of dissolved oxygen sequence, which affects the prediction accuracy. In order to obtain more accurate dissolved oxygen prediction results, decomposition techniques are commonly used to extract the main fluctuations and trends of water quality sequences. However, the high-frequency modes obtained from decomposition are still unstable. To solve this problem, this paper proposed a hybrid prediction model of dissolved oxygen concentration based on secondary decomposition and bidirectional gate recurrent unit. Firstly, dissolved oxygen sequence is preliminarily decomposed by complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and obtain several intrinsic mode functions (IMF). The fuzzy entropy (FE) is calculated to quantify the complexity of the IMF. Then, variational mode decomposition improved by northern goshawk optimization is used to decompose the IMF with higher entropy. The nonlinearity and instability of the sequence are further weakened. Finally, the bidirectional gate recurrent unit (BiGRU) neural network is used to predict each IMF component, and the final prediction result is obtained by reconstructing the prediction results of each component. In order to verify the effectiveness of the proposed model, this paper selects the dissolved oxygen data of Xin'anjiang Reservoir as the research object. The experimental results show that the RMSE, MAE, MAPE, and R2 of the proposed model are 0.1164, 0.0894, 1.0403%, and 0.9939, respectively, which is best among other comparative prediction models (BP, LSTM, GRU, BiGRU, EMD-BiGRU, CEEMDAN-BiGRU, VMD-BiGRU, and GNO-VMD-BiGRU). Therefore, this model effectively deals with high volatility and nonlinear dissolved oxygen data and provides reference for water environment management and ecological protection.


Assuntos
Água Doce , Redes Neurais de Computação , Entropia , Oxigênio , Qualidade da Água
4.
Exp Cell Res ; 435(1): 113913, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38199479

RESUMO

Ovarian cancer (OC) is a lethal gynecologic cancer and the common cause of death within women worldwide. The polycomb group protein enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase highly expressed in various tumors, including OC. However, the mechanistic basis of EZH2 oncogenic activity in OC remain incompletely understood. Bioinformatics analysis showed that the expression of MAPRE3 was lower in OC tissues than in normal tissues, and was positively correlated with the overall survival. MAPRE3 overexpression decreased cell growth, inducing cell cycle arrest and apoptosis in OC cells, whereas MAPRE3 silencing promoted proliferation and accelerated cell cycle progression of OC cells. The in vivo study validated that overexpression of MAPRE3 impeded tumor formation and growth of OC xenografts in nude mice. In addition, knockdown of EZH2 in OC cells downregulated H3K27me3 expression and increased MAPRE3 expression. Inhibiting EZH2 in OC cells reduced the enrichment of H3K27me3 on the promoter of MAPRE3. Furthermore, MAPRE3 silencing significantly reversed changes in the expression of cell cycle and apoptosis-related markers and cell growth mediated by EZH2 knockdown in OC cells. MAPRE3 functions as a suppressor of OC and is epigenetic repressed by EZH2, suggesting a potential therapeutic strategy for OC by targeting EZH2/MAPRE3 axis.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste , Neoplasias Ovarianas , Animais , Feminino , Humanos , Camundongos , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Epigênese Genética/genética , Regulação Neoplásica da Expressão Gênica/genética , Histonas/metabolismo , Camundongos Nus , Neoplasias Ovarianas/patologia , Complexo Repressor Polycomb 2/genética , Complexo Repressor Polycomb 2/metabolismo
5.
Biomed Chromatogr ; 38(4): e5826, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38205667

RESUMO

Artemisia argyi H.Lév. & Vaniot essential oil (AAEO) has shown pharmacological effects such as anti-inflammation, antioxidant, and anti-tumor properties. However, the protective effect of AAEO on lipopolysaccharide (LPS)-induced liver injury and its potential protective mechanism are still unclear. In this study, we used ultra-performance liquid chromatography tandem mass spectrometry metabolomics techniques to investigate the changes in liver tissue metabolites in mice exposed to LPS with or without AAEO treatment for 14 days. The biochemical results showed that compared with the control group, AAEO significantly reduced the levels of liver functional enzymes, suggesting a significant improvement in liver injury. In addition, the 18 differential metabolites identified by metabolomics were mainly involved in the reprogramming of arachidonic acid metabolism, tryptophan metabolism, and purine metabolism. AAEO could significantly inhibit the expression of COX-2, IDO1, and NF-κB; enhance the body's anti-inflammatory ability; and alleviate liver injury. In summary, our study identified the protective mechanism of AAEO on LPS-induced liver injury at the level of small molecular metabolites, providing a potential liver protective agent for the treatment of LPS-induced liver injury.


Assuntos
Artemisia , Doença Hepática Crônica Induzida por Substâncias e Drogas , Óleos Voláteis , Camundongos , Animais , Artemisia/química , Óleos Voláteis/farmacologia , Lipopolissacarídeos/efeitos adversos , Espectrometria de Massas em Tandem , Espectrometria de Massa com Cromatografia Líquida , Metabolômica
6.
Phys Chem Chem Phys ; 26(7): 6049-6057, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38295372

RESUMO

Boron-based complex clusters are a fertile ground for the exploration of exotic chemical bonding and dynamic structural fluxionality. Here we report on the computational design of a ternary MgTa2B6 cluster via global structural searches and quantum chemical calculations. The cluster turns out to be a new member of the molecular rotor family, closely mimicking a turning clock at the subnanoscale. It is composed of a hexagonal B6 ring with a capping Ta atom at the top and bottom, whereas the Mg atom is linked to one Ta site as a radial Ta-Mg dimer. These components serve as the dial, axis, and hand of a nanoclock, respectively. Chemical bonding analyses reveal that the inverse sandwich Ta2B6 motif in the cluster features 6π/6σ double aromaticity, whose electron counting conforms to the (4n + 2) Hückel rule. The Ta-Mg dimer has a Lewis-type σ bond, and the Mg site has negligible bonding with B6 ring. The ternary cluster can be formulated as an [Mg]0[Ta2B6]0 complex. Molecular dynamics simulations suggest that the cluster is structurally fluxional analogous to a nanoclock, even at a low temperature of 100 K. The Ta-Mg hand turns almost freely around the Ta2 axis and along the B6 dial. The tiny intramolecular rotation barrier is less than 0.3 kcal mol-1, being dictated by the bonding nature of double 6π/6σ aromaticity. The present system offers a new type of molecular rotor in physical chemistry.

7.
Life Sci ; 334: 122222, 2023 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-38084673

RESUMO

AIM: Deep brain stimulation (DBS) is currently under investigation as a potential therapeutic approach for managing major depressive disorder (MDD) and ventromedial prefrontal cortex (vmPFC) is recognized as a promising target region. Therefore, the present study aimed to investigate a preclinical paradigm of bilateral vmPFC DBS and examine the molecular mechanisms underlying its antidepressant-like effects using chronic unpredictable stress (CUS) model in rats. MAIN METHODS: Male rats were subjected to stereotaxic surgery and deep brain stimulation paradigm in non-stressed and CUS rats respectively, and the therapeutic effect of DBS were assessed by a series of behavioral tests including sucrose preference test, open field test, elevated plus maze test, and forced swim test. The potential involvement of the BDNF/TrkB signaling pathway and its downstream effects in this process were also investigated using western blot. KEY FINDINGS: We identified that a stimulation protocol consisting of 130 Hz, 200 µA, 90 µs pulses administered for 5 h per day over a period of 7 days effectively mitigated CUS-induced depressive-like and anxiety-like behaviors in rats. These therapeutic effects were associated with the enhancement of the BDNF/TrkB signaling pathway and its downstream ERK1/2 activity. SIGNIFICANCE: These findings provide valuable insights into the potential clinical utility of vmPFC DBS as an approach of improving the symptoms experienced by individuals with MDD. This evidence contributes to our understanding of the neurobiological basis of depression and offers promise for the development of more effective treatments.


Assuntos
Estimulação Encefálica Profunda , Transtorno Depressivo Maior , Ratos , Masculino , Animais , Depressão/tratamento farmacológico , Estimulação Encefálica Profunda/métodos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Córtex Pré-Frontal/metabolismo , Transdução de Sinais , Estresse Psicológico/tratamento farmacológico , Hipocampo/metabolismo , Modelos Animais de Doenças
8.
PeerJ ; 11: e16462, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38025750

RESUMO

Passive acoustic monitoring technology is widely used to monitor the diversity of vocal animals, but the question of how to quickly extract effective sound patterns remains a challenge due to the difficulty of distinguishing biological sounds within multiple sound sources in a soundscape. In this study, we address the potential application of the VGGish model, pre-trained on Google's AudioSet dataset, for the extraction of acoustic features, together with an unsupervised clustering method based on the Gaussian mixture model, to identify various sound sources from a soundscape of a subtropical forest in China. The results show that different biotic and abiotic components can be distinguished from various confounding sound sources. Birds and insects were the two primary biophony sound sources, and their sounds displayed distinct temporal patterns across both diurnal and monthly time frames and distinct spatial patterns in the landscape. Using the clustering and modeling method of the general sound feature set, we quickly depicted the soundscape in a subtropical forest ecosystem, which could be used to track dynamic changes in the acoustic environment and provide help for biodiversity and ecological environment monitoring.


Assuntos
Ecossistema , Som , Animais , Florestas , Acústica , China
9.
BMJ Open ; 13(9): e074677, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37751958

RESUMO

INTRODUCTION: Sleep disorders are clinical syndromes of disturbed sleep-wake rhythms and abnormal sleep quality. They have various causes, but their main manifestations are difficulty falling asleep, sleep disruption and daytime fatigue. These are common clinical symptoms in perioperative patients, especially in gynaecological patients. There is a lack of research on the factors influencing perioperative sleep disorders in gynaecological patients. The aim of this study is to assess the prevalence of sleep disorders in gynaecological surgery patients and to analyse the possible factors influencing them to provide new ideas for improving sleep disorders in this patient population. METHODS AND ANALYSIS: This cross-sectional, descriptive and observational survey is planned to include 480 gynaecological day surgery patients. All patients who meet the inclusion criteria are eligible to join the study. The study will record preoperative diagnosis, surgical procedure, duration of surgery, type of anaesthesia, anaesthetic drugs, sleep quality, anxiety and depression levels and pain indices 30 days before and 1, 2, 3 and 30 days after surgery. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Beijing Shijitan Hospital Affiliated with Capital Medical University (Approval Number: sjtkyll-lx-2022(109)) before the start of recruitment. The results of the study will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200064533.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Transtornos do Sono-Vigília , Humanos , Estudos Transversais , Sono , Transtornos do Sono-Vigília/epidemiologia
10.
Addict Biol ; 28(10): e13330, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37753572

RESUMO

The susceptibility to drug cravings evoked by stimuli poses a formidable hurdle in the treatment of addiction and the prevention of relapse. Pharmacological interventions targeting drug-associated memories hold promise for curbing relapse by impeding the process of memory reconsolidation, predominantly governed by cAMP signalling. Exchange Protein Activated by cAMP (Epac) serves as a distinctive mediator of cAMP signalling, which has been implicated in reinforcing the effects of cocaine and facilitating the acquisition. Nonetheless, the role of Epac in heroin-related memory and the subsequent seeking behaviour remains enigmatic. In this study, we explored the impact of Epac activation on the reconsolidation process of drug-related memories associated with heroin self-administration. Over the course of 10 consecutive days, rats underwent training, wherein they acquired the behaviour of nose poking to obtain heroin accompanied by a tone + light cue. This nose-poking behaviour was subsequently extinguished when heroin infusion and cue presentation were discontinued. Subsequently, we administered 8-pCPT-cAMP (8-CPT), an Epac-specific activator, into the basolateral amygdala at various time points, either in the presence or absence of a conditioned stimulus. Our findings demonstrate that administering 8-CPT immediately after memory retrieval effectively reduces cue- and heroin-induced reinstatement, with the observed effects persisting significantly for a minimum of 28 days. However, infusion of 8-CPT for a duration of 6 h following the memory retrieval trial, or without it altogether, had no discernible impact. Thus, these findings strongly suggest that Epac activation can disrupt the reconsolidation of heroin-associated memory, thereby diminishing the reinstatement of heroin-seeking behaviour.


Assuntos
Cocaína , Heroína , Ratos , Animais , Tonsila do Cerebelo , Ratos Sprague-Dawley , Cocaína/farmacologia , Recidiva , Sinais (Psicologia) , Extinção Psicológica , Autoadministração
11.
J Pharm Biomed Anal ; 234: 115574, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37481900

RESUMO

Allergic rhinitis (AR) is a common allergic disease characterized by nasal congestion, rhinorrhoea, and sneezing. Cineole, a monoterpenoid compound widely present in various volatile oils, has a wide range of pharmacological activities and is of interest in allergic airway diseases for its anti-inflammatory and anti-mucus production abilities. However, the protective effects of cineole in mice with allergic rhinitis and its mechanisms have not been well investigated. In this study, the protective effect of cineole against ovalbumin-induced (OVA-induced) allergic rhinitis and its molecular mechanism is investigated by metabolomic analysis based on ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). OVA combined with aluminum hydroxide adjuvant is used to sensitize and establish the allergic rhinitis (AR) mouse model. The mice are randomly divided into groups of control, AR, cineole (30 mg/kg), and budesonide (38.83 µg/kg). The pharmacodynamic results show that cineole significantly reduces the levels of Th2-type cytokines and OVA-specific IgE (OVA-sIgE) in AR mice, improves nasal mucosal tissue damage and alleviates nasal symptoms compared to the untreated AR group. Metabolomic results show that arachidonic acid (AA) metabolism and tryptophan (Trp) metabolism are reprogrammed on the basis of 27 significantly altered metabolites. Further studies show that cineole inhibits the biosynthesis of pro-inflammatory lipid mediators leukotrienes (LTs) and prostaglandins (PGs) in mice by inhibiting the activity of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) in the arachidonic acid metabolic (AA metabolic) pathway. It also inhibits the production of Th2 cytokines and inflammatory cell infiltration, thereby alleviating symptoms such as nasal congestion and nasal leakage. These results reveal the action and molecular mechanism of cineole in alleviating AR and provide a theoretical basis for the clinical application of cineole in treating AR.


Assuntos
Prostaglandinas , Rinite Alérgica , Camundongos , Animais , Eucaliptol/uso terapêutico , Prostaglandinas/efeitos adversos , Ácido Araquidônico , Cromatografia Líquida , Imunoglobulina E , Espectrometria de Massas em Tandem , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/tratamento farmacológico , Citocinas , Leucotrienos/efeitos adversos , Metabolômica , Ovalbumina , Modelos Animais de Doenças , Camundongos Endogâmicos BALB C
12.
Environ Toxicol ; 38(10): 2416-2428, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37347548

RESUMO

The environmental pollutant bisphenol A (BPA), used in the manufacture of plastic packaging materials for various diets, is widely distributed in the environment and causes severe hepatotoxicity by inducing oxidative stress. Artemisia argyi essential oil (AAEO), a volatile oil component isolated from Artemisia argyi H.Lév. & Vaniot, has pharmacological effects, especially for hepatoprotective actions. However, the potential effect of AAEO in BPA induced hepatotoxicity has not been characterized. First, we analyzed the chemical composition in AAEO by gas chromatography-mass spectrometry. Herein, we investigated the effect of AAEO on hepatic metabolic changes in mice exposed to BPA. Results showed that compared with the BPA group, AAEO could reduce the level of liver function enzymes in BPA mice serum, and ameliorate hepatic lesions and fibrosis. Additionally, 20 differential metabolites screened by metabolomics were mainly involved in the reprogramming of glutathione metabolism, purine metabolism, and polyunsaturated fatty acid synthesis. Moreover, AAEO could reduce hepatic ferroptosis induced by BPA, as demonstrated by reducing xanthine oxidase activity, up-regulating the activities of glutathione peroxidase 4 (GPX4), superoxide dismutase, and catalase and the expression of SLC7A11 to promote the glutathione synthetic, while inhibiting transferrin receptor 1 (TFR1) expression to reduce the accumulation of Fe2+ in cells. Therefore, our study identified AAEO as a hepatic protectant against BPA-induced hepatotoxicity by reversing the occurrence of ferroptosis.


Assuntos
Artemisia , Doença Hepática Induzida por Substâncias e Drogas , Ferroptose , Óleos Voláteis , Camundongos , Animais , Artemisia/química , Óleos Voláteis/farmacologia , Glutationa , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle
13.
Microbiol Spectr ; 11(3): e0471122, 2023 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-37125940

RESUMO

Mycobacterium tuberculosis (Mtb) continues to pose a significant threat to global health because it causes granulomas and systemic inflammatory responses during active tuberculosis (TB). Mtb can induce macrophage pyroptosis, which results in the release of IL-1ß and causes tissue damage, thereby promoting its spread. In the absence of anti-TB drugs, host-directed therapy (HDT) has been demonstrated to be an effective strategy against TB. In this study, we used an in vitro Mtb-infected macrophage model to assess the effect of baicalein, derived from Scutellariae radix, on pyroptosis induced in Mtb-infected macrophages. Further, we investigated the molecular mechanisms underlying the actions of baicalein. The results of the study suggest that baicalein inhibits pyroptosis in Mtb-infected macrophages by downregulating the assembly of AIM2 and NLRP3 inflammasome and promoting autophagy. Further research has also shown that the mechanism by which baicalein promotes autophagy may involve the inhibition of the activation of the Akt/mTOR pathway and the inhibition of the AIM2 protein, which affects the levels of CHMP2A protein required to promote autophagy. Thus, our data show that baicalein can inhibit Mtb infection-induced macrophage pyroptosis and has the potential to be a new adjunctive HDT drug. IMPORTANCE Current strategies for treating drug-resistant tuberculosis have limited efficacy and undesirable side effects; hence, research on new treatments, including innovative medications, is required. Host-directed therapy (HDT) has emerged as a viable strategy for modulating host cell responses in order to enhance protective immunity against infections. Baicalein, extracted from Scutellariae radix, was shown to inhibit pyroptosis caused by Mycobacterium tuberculosis-infected macrophages and was associated with autophagy. Our findings reveal that baicalein can be used as an adjunctive treatment for tuberculosis or other inflammatory diseases by regulating immune function and enhancing the antibacterial ability of the host. It also provides a new idea for exploring the anti-inflammatory mechanism of baicalein.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Piroptose , Macrófagos , Autofagia , Proteínas de Ligação a DNA/metabolismo
14.
Inflammation ; 46(5): 1749-1763, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37212951

RESUMO

As a lethal infectious disease, tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb). Its complex pathophysiological process limits the effectiveness of many clinical treatments. By regulating host cell death, Mtb manipulates macrophages, the first line of defense against invading pathogens, to evade host immunity and promote the spread of bacteria and intracellular inflammatory substances to neighboring cells, resulting in widespread chronic inflammation and persistent lung damage. Autophagy, a metabolic pathway by which cells protect themselves, has been shown to fight intracellular microorganisms, such as Mtb, and they also play a crucial role in regulating cell survival and death. Therefore, host-directed therapy (HDT) based on antimicrobial and anti-inflammatory interventions is a pivotal adjunct to current TB treatment, enhancing anti-TB efficacy. In the present study, we showed that a secondary plant metabolite, ursolic acid (UA), inhibited Mtb-induced pyroptosis and necroptosis of macrophages. In addition, UA induced macrophage autophagy and enhanced intracellular killing of Mtb. To investigate the underlying molecular mechanisms, we explored the signaling pathways associated with autophagy as well as cell death. The results showed that UA could synergistically inhibit the Akt/mTOR and TNF-α/TNFR1 signaling pathways and promote autophagy, thus achieving its regulatory effects on pyroptosis and necroptosis of macrophages. Collectively, UA could be a potential adjuvant drug for host-targeted anti-TB therapy, as it could effectively inhibit pyroptosis and necroptosis of macrophages and counteract the excessive inflammatory response caused by Mtb-infected macrophages via modulating the host immune response, potentially improving clinical outcomes.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Mycobacterium tuberculosis/fisiologia , Fator de Necrose Tumoral alfa/metabolismo , Ácido Ursólico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Piroptose , Necroptose , Macrófagos/metabolismo , Tuberculose/metabolismo , Transdução de Sinais , Autofagia , Serina-Treonina Quinases TOR/metabolismo
15.
Front Public Health ; 11: 1119630, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37006555

RESUMO

Objective: The purpose of this study was to translate and verify the reliability and validity of the Chinese version of the self-care scale for older adults undergoing hip fracture surgery. Methods: A total of 502 older adult/adults patients after hip fracture surgery were recruited from Liaoning, Shanxi, and Beijing, China. The reliability of the Chinese version of the scale was measured by internal consistency, split-half reliability, and retest reliability, and the validity was evaluated by the content validity index and structure validity index. Results: The Chinese version of the HFS-SC scale had a Cronbach's alpha coefficient of 0.848, and the Cronbach's alpha coefficients for the five dimensions ranged from 0.719 to 0.780. The split-half reliability of the scale was 0.739, and the retest reliability was 0.759. The content validity index (S-CVI) was 0.932. The five-factor structure, supported by the eigenvalues, total variance explained, and the scree plot accounted for 66.666% of the total variance. In confirmatory factor analysis, the model fit results were as follows, X2/df = 1.847, GFI = 0.914, AGFI = 0.878, PGFI = 0.640, IFI = 0.932, TLI = 0.912, CFI = 0.931, RMSEA = 0.058, PNFI = 0.679. The indicators of the model's fit were within reasonable bounds. Conclusion: The Chinese version of the self-care scale for older adults undergoing hip fracture surgery has suitable reliability and validity. The scale can be used to assess the level of older adult/adults self-care in China following hip replacement surgery and serves as a useful benchmark for identifying potential intervention targets to raise the level of older adult/adults self-care following hip replacement surgery.


Assuntos
Autocuidado , Humanos , Idoso , Inquéritos e Questionários , Psicometria , Reprodutibilidade dos Testes , China
16.
J Pharm Biomed Anal ; 229: 115380, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37011550

RESUMO

Quantification of substances in biofluid samples (e.g., urine, blood, and cerebrospinal fluids) are useful for clinical diagnosis. In current study, a rapid and green strategy by coupling in-syringe kapok fiber-supported liquid-phase microextraction with flow-injection mass spectrometry was proposed. The natural kapok fiber was used as an oily extraction solvent (e.g., n-octanol) support material, and an in-syringe extraction device was conveniently constructed. The whole extraction processes, including sampling, washing and desorption, were conveniently conducted by simply pulling/pushing the syringe plunger, enabling rapid analyte enrichment and sample purification. The follow-up flow injection-mass spectrometry detection enabled rapid and high throughput analysis. As an example, the proposed method was applied to analyze antidepressants in plasma/urine, showing satisfied linearities (R2 ≥0.993) in ranges of 0.2-1000 ng/mL. By employing the in-syringe extraction method prior to flow injection-mass spectrometry detection, the LOQs in plasma and urine were reduced by 25-80 folds and 5-25 folds, respectively. Besides, by employing ethanol and 80% ethanol as the desorption solvent and carrier solvent, respectively, the analytical method showed excellent greenness. In general, the integrated method provides a promising choice for rapid and green biofluid analysis.


Assuntos
Microextração em Fase Líquida , Seringas , Antidepressivos , Solventes/química , Espectrometria de Massas , Etanol , Microextração em Fase Líquida/métodos
18.
Langmuir ; 39(18): 6580-6591, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37105201

RESUMO

Magnesium-ion batteries (MIBs) have been pushed into the research boom in the post-lithium-ion batteries era due to their low cost, no dendrite hazard, and high capacity. However, finding suitable cathode materials to improve the slow kinetics of Mg2+ is an ongoing challenge. In this work, Ba0.18V2O4.95/NH4V4O10 film electrodes were grown in one step on indium tin oxide (ITO) conductive glass using a low-temperature liquid-phase deposition method. Temperature was used as the probe condition, and it was concluded that the films annealed at 400 °C had suitable crystallinity and de-ammonium lattice space. At lower current density, with 0.5 M Mg(ClO4)2/PC as the electrolyte, it exhibited an initial discharge capacity of 130.99 mA h m-2 at 210 mA m-2 and 106.52% capacity retention after 100 cycles. In addition, it exhibited excellent electrochemical performance in long-term cycling (92.98% capacity retention after 300 cycles at 600 mA m-2). According to the results of ex situ X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and high-resolution transmission electron microscopy (HRTEM), the removal of NH4+ created more lattice space, assisting Ba0.18V2O4.95 to increase the transfer channels of Mg2+, providing more active sites to promote diffusion kinetics (the average DMg2+ was 2.07 × 10-12 cm2 s-1) and specific capacity. Therefore, these film electrodes for scalable Mg2+ storage are promising MIB cathode candidates that exhibit good performance advantages in storage applications.

19.
Environ Sci Pollut Res Int ; 30(6): 16266-16276, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36181592

RESUMO

Honey bees (Apis spp.) are often used as biological indicators of environmental changes. Recently, bees have been explored to monitor air contaminants by listening to the beehive sound. The beehive sound is believed to encode information on bee responses to chemicals outside their hives. Here we conducted an experiment to address this. First, we randomly fed colonies with pure syrup (PS), acetone-laced syrup (AS), or ethyl acetate-laced syrup (ES) in front of the beehives and collect the beehive sound. Based on the audio data, we build machine learning (ML) models to identify the types of syrup. The result shows that ML models achieved over 90% accuracy for identifying syrup types, indicating that the bees inside their hives emitted the sound associated with the chemicals outside their hives. Then, we sequentially fed the colonies in the order of PS, ES, and AS (the first session) and again in the reverse order (the second session), but did not remove the accumulated ES or AS in the alternative feeding experiment. Based on the audio data, the identification accuracy of both ES and AS by the ML model built on the randomly feeding experiment was different, indicating that the accumulated chemical residuals could confuse the ML models. Therefore, the beehive sound-based environmental monitoring should simultaneously consider the responses of bees to the chemicals outside their hives and their responses to those accumulated inside their hives, which may act simultaneously.


Assuntos
Monitoramento Ambiental , Urticária , Abelhas , Animais , Alimentos , Biomarcadores Ambientais
20.
Transl Psychiatry ; 12(1): 530, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-36587026

RESUMO

Repeated cocaine exposure causes compensatory neuroadaptations in neurons in the nucleus accumbens (NAc), a region that mediates reinforcing effects of drugs. Previous studies suggested a role for adenosine monophosphate-activated protein kinase (AMPK), a cellular energy sensor, in modulating neuronal morphology and membrane excitability. However, the potential involvement of AMPK in cocaine use disorder is still unclear. The present study employed a cocaine self-administration model in rats to investigate the effect of AMPK and its target cyclic adenosine monophosphate response element binding protein-regulated transcriptional co-activator 1 (CRTC1) on cocaine reinforcement and the motivation for cocaine. We found that intravenous cocaine self-administration significantly decreased AMPK activity in the NAc shell (NAcsh), which persisted for at least 7 days of withdrawal. Cocaine reinforcement, reflected by self-administration behavior, was significantly prevented or enhanced by augmenting or suppressing AMPK activity pharmacologically and genetically, respectively. No difference in sucrose self-administration behavior was found after the same manipulations. The inhibition of AMPK activity in the NAcsh also increased the motivation for cocaine in progressive-ratio schedules of reinforcement, whereas the activation of AMPK had no effect. The knockdown of CRTC1 in the NAcsh significantly impaired cocaine reinforcement, which was rescued by pharmacologically increasing AMPK activity. Altogether, these results indicate that AMPK in the NAcsh is critical for cocaine reinforcement, possibly via the regulation of CRTC1 signaling. These findings may help reveal potential therapeutic targets and have important implications for the treatment of cocaine use disorder and relapse.


Assuntos
Cocaína , Ratos , Animais , Cocaína/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Ratos Sprague-Dawley , Reforço Psicológico , Fatores de Transcrição/metabolismo , Monofosfato de Adenosina/metabolismo , Monofosfato de Adenosina/farmacologia , Núcleo Accumbens , Autoadministração
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA