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Four previously undescribed isoprenoid flavonoids (2-5) were isolated from Sophora davidii, along with five known analogues. The structures of the compounds were established through comprehensive analysis of spectroscopic data, including HRESIMS, 1D and 2D NMR, and absolute configurations determined by theoretical calculations, including ECD and NMR calculation. The cytotoxic effects of the isolated compounds on human HT29 colon cancer cells were evaluated using the MTT assay, compound 1 exhibited cytotoxicity against human HT29 colon cancer cells with an IC50 value of 8.39 ± 0.09 µM. Studies conducted with compound 1 in HT29 cells demonstrated that it may induce apoptosis and autophagy in HT29 by promoting the phosphorylation of P38 MAPK and inhibiting the phosphorylation of Erk MAPK.
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Antineoplásicos Fitogênicos , Apoptose , Autofagia , Flavonoides , Sophora , Humanos , Sophora/química , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Células HT29 , Estrutura Molecular , Flavonoides/farmacologia , Flavonoides/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , China , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Terpenos/farmacologia , Terpenos/isolamento & purificação , FosforilaçãoRESUMO
Uridine diphosphate glycosyltransferase(UGT) is involved in the glycosylation of a variety of secondary metabolites in plants and plays an important role in plant growth and development and regulation of secondary metabolism. Based on the genome of a diploid Chrysanthemum indicum, the UGT gene family from Ch. indicum was identified by bioinformatics methods, and the physical and chemical properties, subcellular localization prediction, conserved motif, phylogeny, chromosome location, gene structure, and gene replication events of UGT protein were analyzed. Transcriptome and real-time fluorescence quantitative polymerase chain reaction(PCR) were used to analyze the expression pattern of the UGT gene in flowers and leaves of Ch. indicum. Quasi-targeted metabolomics was used to analyze the differential metabolites in flowers and leaves. The results showed that a total of 279 UGT genes were identified in the Ch. indicum genome. Phylogenetic analysis showed that these UGT genes were divided into 8 subfamilies. Members of the same subfamily were distributed in clusters on the chromosomes. Tandem duplications were the main driver of the expansion of the UGT gene family from Ch. indicum. Structural domain analysis showed that 262 UGT genes had complete plant secondary metabolism signal sequences(PSPG box). The analysis of cis-acting elements indicated that light-responsive elements were the most ubiquitous elements in the promoter regions of UGT gene family members. Quasi-targeted metabolome analysis of floral and leaf tissue revealed that most of the flavonoid metabolites, including luteolin-7-O-glucoside and kaempferol-7-O-glucoside, had higher accumulation in flowers. Comparative transcriptome analysis of flower and leaf tissue showed that there were 72 differentially expressed UGT genes, of which 29 genes were up-regulated in flowers, and 43 genes were up-regulated in leaves. Correlation network and phylogenetic analysis showed that CindChr9G00614970.1, CindChr2G00092510.1, and CindChr2G00092490.1 may be involved in the synthesis of 7-O-flavonoid glycosides in Ch. indicum, and real-time fluorescence quantitative PCR analysis further confirmed the reliability of transcriptome data. The results of this study are helpful to understand the function of the UGT gene family from Ch. indicum and provide data reference and theoretical basis for further study on the molecular regulation mechanism of flavonoid glycosides synthesis in Ch. indicum.
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Chrysanthemum , Glicosiltransferases , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Chrysanthemum/genética , Difosfato de Uridina , Filogenia , Reprodutibilidade dos Testes , Plantas/metabolismo , Flavonoides , Glicosídeos , Regulação da Expressão Gênica de PlantasRESUMO
OBJECTIVE: To investigate the clinical efficacy of fire acupuncture (FA) on plaque psoriasis (PP), exploring its suitable syndrome types, in order to achieve better therapeutic effects, accelerate the possibility of psoriasis skin lesion recovery, and provide assistance for clinical treatment. METHODS: A total of 8 patients with PP aged between 18 and 60 years were recruited and treated with FA once a week, and the lesion area and severity index (PASI), visual analog scale and pruritus were measured before, 2, 4 and 8 weeks after treatment and at the follow-up period (week 12), respectively. Visual analog scale, and dermoscopy were used for assessment. RESULTS: All patients showed improvement in pruritus after 1 FA treatment, and lesions were reduced to varying degrees after 2 weeks. Except for patients 5 and 8, who only achieved effective results due to severe disease, all other patients with psoriasis achieved significant results at 8 weeks after treatment. CONCLUSION: FA can significantly control the development of lesions, reduce the symptoms of PP lesions and pruritus, and help prevent psoriasis recurrence.
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Terapia por Acupuntura , Psoríase , Humanos , Lactente , Psoríase/tratamento farmacológico , Resultado do Tratamento , Prurido/etiologia , Prurido/terapia , Pesquisa , Índice de Gravidade de Doença , Método Duplo-CegoRESUMO
Litter input triggers the secretion of soil extracellular enzymes and facilitates the release of carbon (C), nitrogen (N), and phosphorus (P) from decomposing litter. However, how soil extracellular enzyme activities were controlled by litter input with various substrates is not fully understood. We examined the activities and stoichiometry of five enzymes including ß-1,4-glucosidase, ß-D-cellobiosidase, ß-1,4-N-acetyl-glucosaminidase, leucine aminopeptidase and acidic phosphatase (AP) with and without litter input in 10-year-old Castanopsis carlesii and Cunninghamia lanceolata plantations monthly during April to August, in October, and in December 2021 by using an in situ microcosm experiment. The results showed that: 1) There was no significant effect of short-term litter input on soil enzyme activity, stoichiometry, and vector properties in C. carlesii plantation. In contrast, short-term litter input significantly increased the AP activity by 1.7% in May and decreased the enzymatic C/N ratio by 3.8% in August, and decreased enzymatic C/P and N/P ratios by 11.7% and 10.3%, respectively, in October in C. lanceolata plantation. Meanwhile, litter input increased the soil enzymatic vector angle to 53.8° in October in C. lanceolata plantations, suggesting a significant P limitation for soil microorganisms. 2) Results from partial least squares regression analyses showed that soil dissolved organic matter and microbial biomass C and N were the primary factors in explaining the responses of soil enzymatic activity to short-term litter input in both plantations. Overall, input of low-quality (high C/N) litter stimulates the secretion of soil extracellular enzymes and accelerates litter decomposition. There is a P limitation for soil microorganisms in the study area.
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Carbono , Cunninghamia , Fagaceae , Nitrogênio , Fósforo , Microbiologia do Solo , Solo , Solo/química , Cunninghamia/crescimento & desenvolvimento , Cunninghamia/metabolismo , Carbono/metabolismo , Carbono/análise , Nitrogênio/metabolismo , Nitrogênio/análise , Fósforo/metabolismo , Fósforo/análise , Fagaceae/crescimento & desenvolvimento , Fagaceae/metabolismo , Leucil Aminopeptidase/metabolismo , Celulose 1,4-beta-Celobiosidase/metabolismo , Ecossistema , Folhas de Planta/metabolismo , Folhas de Planta/química , Acetilglucosaminidase/metabolismo , Fosfatase Ácida/metabolismo , beta-Glucosidase/metabolismo , ChinaRESUMO
The root of Aconitum carmichaelii Debx. (Fuzi) is an herbal medicine used in China that exerts significant efficacy in rescuing patients from severe diseases. A key toxic compound in Fuzi, aconitine (AC), could trigger unpredictable cardiotoxicities with high-individualization, thus hinders safe application of Fuzi. In this study we investigated the individual differences of AC-induced cardiotoxicities, the biomarkers and underlying mechanisms. Diversity Outbred (DO) mice were used as a genetically heterogeneous model for mimicking individualization clinically. The mice were orally administered AC (0.3, 0.6, 0.9 mg· kg-1 ·d-1) for 7 d. We found that AC-triggered cardiotoxicities in DO mice shared similar characteristics to those observed in clinic patients. Most importantly, significant individual differences were found in DO mice (variation coefficients: 34.08%-53.17%). RNA-sequencing in AC-tolerant and AC-sensitive mice revealed that hemoglobin subunit beta (HBB), a toxic-responsive protein in blood with 89% homology to human, was specifically enriched in AC-sensitive mice. Moreover, we found that HBB overexpression could significantly exacerbate AC-induced cardiotoxicity while HBB knockdown markedly attenuated cell death of cardiomyocytes. We revealed that AC could trigger hemolysis, and specifically bind to HBB in cell-free hemoglobin (cf-Hb), which could excessively promote NO scavenge and decrease cardioprotective S-nitrosylation. Meanwhile, AC bound to HBB enhanced the binding of HBB to ABHD5 and AMPK, which correspondingly decreased HDAC-NT generation and led to cardiomyocytes death. This study not only demonstrates HBB achievement a novel target of AC in blood, but provides the first clue for HBB as a novel biomarker in determining the individual differences of Fuzi-triggered cardiotoxicity.
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Proteínas Quinases Ativadas por AMP , Aconitina , Cardiotoxicidade , Histona Desacetilases , Animais , Camundongos , Cardiotoxicidade/metabolismo , Cardiotoxicidade/etiologia , Histona Desacetilases/metabolismo , Proteínas Quinases Ativadas por AMP/metabolismo , Masculino , Humanos , Aconitum/química , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Medicamentos de Ervas Chinesas/farmacologiaRESUMO
OBJECTIVES: This review examined the effectiveness of using dance movement therapy (DMT) and dance movement interventions (DMIs) with cancer and palliative care patients. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Six databases were searched from inception to July 9, 2022, without limits on year or age. Searching was updated on July 10, 2023. The risk of bias was assessed by the Cochrane (RoB 2) and ROBINS-I tools. Meta-analyses were conducted to pool estimates of the effects of DMT and DMI on patients' health-related outcomes. A narrative synthesis of outcomes was performed where meta-analysis was not appropriate. RESULTS: Among a total of 16 studies included in this review, nine were randomized controlled trials and seven were non-randomized trials, with a total of 893 participants. Only six of these studies were fully or partially described as true DMTs (some with less clarity than others), whereas the majority (n = 10) were DMIs with unclear therapeutic alignment. Most studies focused on female patients with breast cancer. Cancer patients undergoing palliative care received little attention. The overall risk of bias from the evaluated studies was high. Meta-analysis of two trials revealed that DMTs had no effect on QOL in cancer patients (SMD - 0.09, 95% CI - 0.21-0.40, P = 0.54), while narrative analysis and non-randomized trials showed no overall effect of DMTs on anxiety, depression, body image, self-esteem, or sleep disturbance but significant positive effects on perceived stress, pain severity, and pain interference. DMIs had significant positive effects on cancer patients' depression (SMD - 0.53, 95% CI - 0.93 to - 0.14, P = 0.008) and fatigue (SMD - 0.42, 95% CI - 0.70 to - 0.14, P = 0.003). DMI trials synthesized narratively showed an effect on patients' body image, self-esteem, physical function, right and left handgrip strength, life satisfaction, and the mental component of QOL. CONCLUSION: Both DMT and DMIs had promising effects on several health outcomes, but results were inconsistent, and the evidence was weak. The reviewed studies' low evidence quality and small sample sizes affected the findings' robustness and reliability. Large-scale, high-quality randomized controlled trials with sufficient sample sizes, and clear and veracious DMT and DMI protocols and data are required to provide more credible research evidence and influence practice.
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Neoplasias da Mama , Dançaterapia , Dança , Feminino , Humanos , Dançaterapia/métodos , Depressão/terapia , Força da Mão , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , MasculinoRESUMO
The cell membrane is a crucial component of cells, protecting their integrity and stability while facilitating signal transduction and information exchange. Therefore, disrupting its structure or impairing its functions can potentially cause irreversible cell damage. Presently, the tumor cell membrane is recognized as a promising therapeutic target for various treatment methods. Given the extensive research focused on cell membranes, it is both necessary and timely to discuss these developments, from materials design to specific biomedical applications. This review covers treatments based on functional materials targeting the cell membrane, ranging from well-known membrane-anchoring photodynamic therapy to recent lysosome-targeting chimaeras for protein degradation. The diverse therapeutic mechanisms are introduced in the following sections: membrane-anchoring phototherapy, self-assembly on the membrane, in situ biosynthesis on the membrane, and degradation of cell membrane proteins by chimeras. In each section, we outline the conceptual design or general structure derived from numerous studies, emphasizing representative examples to understand advancements and draw inspiration. Finally, we discuss some challenges and future directions in membrane-targeted therapy from our perspective. This review aims to engage multidisciplinary readers and encourage researchers in related fields to advance the fundamental theories and practical applications of membrane-targeting therapeutic agents.
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Proteínas de Membrana , Neoplasias , Humanos , Membrana Celular/química , Proteínas de Membrana/metabolismo , Fototerapia , Neoplasias/metabolismoRESUMO
The efficacy and safety of different Chinese patent medicines in the treatment of coronary heart disease complicated with heart failure were evaluated by network Meta-analysis. The randomized controlled trial(RCT) of Chinese patent medicines for coronary heart disease complicated with heart failure was retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, Web of Science, EMbase, and Cochrane Library with the time interval from inception to July 5, 2023. The quality of the included RCT was evaluated by the Cochrane's risk of bias assessment tool, and a network Meta-analysis was performed in Stata 16.0. Finally, a total of 82 RCTs were included, involving 9 298 patients and 11 Chinese patent medicines. Network Meta-analysis yielded the following results based on the surface under the cumulative ranking curve(SUCRA).(1)In terms of improving the clinical response rate, the top three interventions were Qishen Yiqi Dripping Pills + conventional western medicine, Zhenyuan Capsules + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(2) In terms of increasing left ventricular ejection fraction(LVEF), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Compound Danshen Dripping Pills + conventional western medicine, and Tongxinluo Capsules + conventional western medicine.(3) In terms of reducing left ventricular end-diastolic diameter(LVEDD), the top three interventions were Shexiang Tongxin Dripping Pills + conventional western medicine, Tongxinluo Capsules + conventional western medicine, and Shexiang Baoxin Pills + conventional western medicine.(4) In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the top three interventions were Shexiang Baoxin Pills + conventional western medicine, Qi-shen Yiqi Dripping Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(5) In terms of reducing hyper-sensitive C-reactive protein(hs-CRP), the top three interventions were Naoxintong Capsules + conventional western medicine, Shexiang Baoxin Pills + conventional western medicine, and Compound Danshen Dripping Pills + conventional western medicine.(6) In terms of increasing the distance of the six-minute walking trail(6MWT), the top three interventions were Zhen-yuan Capsules + conventional western medicine, Qili Qiangxin Capsules + conventional western medicine, and Qishen Yiqi Dripping Pills + conventional western medicine. The results showed that Chinese patent medicines combined with conventional western medicine can effectively improve the clinical response rate, LVEF, and 6MWT and reduce LVEDD, NT-proBNP, and hs-CRP. However, due to the overall low quality of the articles included and the few articles of some Chinese patent medicines, direct comparison between diffe-rent Chinese patent medicines remains to be carried out and the results need to be further verified.
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Doença das Coronárias , Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Humanos , Metanálise em Rede , Medicamentos sem Prescrição/uso terapêutico , Proteína C-Reativa , Volume Sistólico , Função Ventricular Esquerda , Medicamentos de Ervas Chinesas/uso terapêutico , Doença das Coronárias/complicações , Doença das Coronárias/tratamento farmacológico , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológicoRESUMO
This study aims to summarize the research hotspots and trends in traditional Chinese medicine(TCM) treatment of trauma and provide suggestions for collaborative research on the treatment of trauma with integrated Chinese and western medicine. The re-levant research articles on TCM treatment of trauma were searched against CNKI, Wanfang, VIP, Web of Science, and PubMed from inception to December 31, 2022 and analyzed using bibliometric. After screening, 315 articles in Chinese and 34 articles in English were included. The articles were mainly published by TCM journals. The core author groups were absent. The author affiliations were dominated by medical institutions and supplemented by universities, research institutions, and government agencies. The research mainly focused on the clinical practice and trials of TCM in trauma treatment. Although the TCM treatment of trauma emerged early, it is still in the initial stage of development. The future research can focus on innovating the service model of trauma treatment, improving clinical research capability, improving medical quality management, and strengthening the TCM talent teams in comprehensive hospitals. Western medicine is precise and effective in the treatment of trauma, while TCM with unique treatment methods and effects can play a complementary role. Therefore, the trauma treatment with integrated Chinese and western medicine demonstrates a promising prospect.
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Medicina Tradicional Chinesa , Ferimentos e Lesões , Bibliometria , Ferimentos e Lesões/terapiaRESUMO
BACKGROUND: The liver is an important metabolic and digestive organ in the human body, capable of producing bile, clotting factors, and vitamins. AIM: To investigate the recovery of gastrointestinal function in patients after hepatobiliary surgery and identify effective rehabilitation measures. METHODS: A total of 200 patients who underwent hepatobiliary surgery in our hospital in 2022 were selected as the study subjects. They were divided into a control group and a study group based on the extent of the surgery, with 100 patients in each group. The control group received routine treatment, while the study group received targeted interventions, including early enteral nutrition support, drinking water before gas discharge, and large bowel enema, to promote postoperative gastrointestinal function recovery. The recovery of gastrointestinal function was compared between the two groups. RESULTS: Compared with the control group, patients in the study group had better recovery of bowel sounds and less accumulation of fluids in the liver bed and gallbladder fossa (P < 0.05). They also had shorter time to gas discharge and first meal (P < 0.05), higher overall effective rate of gastrointestinal function recovery (P < 0.05), and lower incidence of postoperative complications (P < 0.05). CONCLUSION: Targeted nursing interventions (early nutritional support, drinking water before gas discharge, and enema) can effectively promote gastrointestinal function recovery in patients undergoing hepatobiliary surgery and reduce the incidence of complications, which is worthy of promotion.
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Designing reactive calcium-based nanogenerators to produce excess calcium ions (Ca2+ ) in tumor cells is an attractive tumor treatment method. However, nanogenerators that introduce exogenous Ca2+ are either overactive incapable of on-demand release, or excessively inert incapable of an overload of calcium rapidly. Herein, inspired by inherently diverse Ca2+ -regulating channels, a photo-controlled Ca2+ nanomodulator that fully utilizes endogenous Ca2+ from dual sources was designed to achieve Ca2+ overload in tumor cells. Specifically, mesoporous silica nanoparticles were used to co-load bifunctional indocyanine green as a photodynamic/photothermal agent and a thermal-sensitive nitric oxide (NO) donor (BNN-6). Thereafter, they were coated with hyaluronic acid, which served as a tumor cell-targeting unit and a gatekeeper. Under near-infrared light irradiation, the Ca2+ nanomodulator can generate reactive oxygen species that stimulate the transient receptor potential ankyrin subtype 1 channel to realize Ca2+ influx from extracellular environments. Simultaneously, the converted heat can induce BNN-6 decomposition to generate NO, which would open the ryanodine receptor channel in the endoplasmic reticulum and allow stored Ca2+ to leak. Both in vitro and in vivo experiments demonstrated that the combination of photo-controlled Ca2+ influx and release could enable Ca2+ overload in the cytoplasm and efficiently inhibit tumor growth.
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Nanopartículas , Neoplasias , Humanos , Cálcio , Fototerapia , Neoplasias/tratamento farmacológico , Verde de Indocianina , Retículo EndoplasmáticoRESUMO
The extensive application of Tetrabromobisphenol A (TBBPA) leads to the pollution of part of the water environment and brings great safety risks to aquatic animals. As a natural extract, tea polyphenols (TPs) have antioxidant and anti-inflammatory effects. Gills are one of the immune organs of fish and constitute the first line of defense of the immune system. However, it was unclear whether TPs could mitigate TBBPA-induced gills injury. Therefore, an animal model was established to investigate the effect of TPs on TBBPA-induced gills. The results indicated that TBBPA changed the coefficient and tissue morphology of carp gills. In addition, TBBPA induced oxidative stress and inflammation, leading to ferroptosis and apoptosis in carp gills. Dietary addition of TPs significantly improved the antioxidant capacity of carp, effectively inhibited the overexpression of TLR4/NF-κB and its mediated inflammatory response. Moreover, TPs restored iron metabolism, reduced the expression of pro-apoptotic factors thereby alleviating ferroptosis and apoptosis in carp gills. This study enriched the protective effect of TPs and provided a new way to improve the innate immunity of carp.
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Carpas , Ferroptose , Bifenil Polibromatos , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Antioxidantes/metabolismo , Receptor 4 Toll-Like/genética , Carpas/metabolismo , Brânquias , Polifenóis/farmacologia , Polifenóis/metabolismo , Transdução de Sinais , Proteínas de Peixes , Inflamação/induzido quimicamente , Inflamação/veterinária , Inflamação/metabolismo , Apoptose , Chá/metabolismoRESUMO
The comprehensive study of compound variations in released smoke during the combustion process is a great challenge in many scientific fields related to analytical chemistry like traditional Chinese medicine, environment analysis, food analysis, etc. In this work, we propose a new comprehensive strategy for efficiently and high-thoroughly characterizing compounds in the online released complex smokes: (i) A smoke capture device was designed for efficiently collecting chemical constituents to perform gas chromatography-mass spectrometry (GC-MS) based untargeted analysis. (ii) An advanced data analysis tool, AntDAS-GCMS, was used for automatically extracting compounds in the original acquired GC-MS data files. Additionally, a GC-MS data analysis guided instrumental parameter optimizing strategy was proposed for the optimization of parameters in the smoke capture device. The developed strategy was demonstrated by the study of compound variations in the smoke of traditional Chinese medicine, Artemisia argyi Levl. et Vant. The results indicated that more than 590 components showed significant differences among released smokes of various moxa velvet ratios. Finally, about 88 compounds were identified, of which phenolic compounds were the most abundant, followed by aromatics, alkenes, alcohols and furans. In conclusion, we may provide a novel approach to the studies of compounds in online released smoke.
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Artemisia , Artemisia/química , Medicina Tradicional Chinesa , Fumaça , Cromatografia Gasosa-Espectrometria de Massas/métodosRESUMO
In this work, shrimp shell-derived magnetic NiFe2O4/N, O co-doped porous carbon nanozyme with superior oxidase (OXD)-like activity was prepared and used for colorimetric/photothermal/smartphone dual-signal triple-mode detection of antioxidants in fruits and beverages. The magnetic NiFe2O4/N, O co-doped porous carbon (MNPC) material was triumphantly fabricated using a combined in-situ surface chelation and pyrolysis method. The resultant MNPC composite exhibits a superior OXD-like activity, which can effectively oxidize 3,3',5,5'-tetramethylbenzidine (TMB) for yielding colorimetric/temperature dual-signal (CTDS) in absence of H2O2. This CTDS output sensor was successfully used for the determination of ascorbic acid and tannic acid. The proposed CTDS sensor with good specificity and high sensitivity can satisfy different on-site analysis requirements. Interestingly, the MNPC as a sustainable filler was further used for improving packaging properties of polyvinyl alcohol film. In short, this work offers a large-scale and cheap method to fabricate magnetic carbon-based nanozyme for monitoring antioxidants and ameliorating packaging properties.
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Óxido de Alumínio , Antioxidantes , Peróxido de Hidrogênio , Óxido de Magnésio , Polifenóis , Porosidade , Carbono , ColorimetriaRESUMO
To survive in a complex social group, one needs to know who to approach and, more importantly, who to avoid. In mice, a single defeat causes the losing mouse to stay away from the winner for weeks1. Here through a series of functional manipulation and recording experiments, we identify oxytocin neurons in the retrochiasmatic supraoptic nucleus (SOROXT) and oxytocin-receptor-expressing cells in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part (aVMHvlOXTR) as a key circuit motif for defeat-induced social avoidance. Before defeat, aVMHvlOXTR cells minimally respond to aggressor cues. During defeat, aVMHvlOXTR cells are highly activated and, with the help of an exclusive oxytocin supply from the SOR, potentiate their responses to aggressor cues. After defeat, strong aggressor-induced aVMHvlOXTR cell activation drives the animal to avoid the aggressor and minimizes future defeat. Our study uncovers a neural process that supports rapid social learning caused by defeat and highlights the importance of the brain oxytocin system in social plasticity.
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Agressão , Aprendizagem da Esquiva , Hipotálamo , Vias Neurais , Neurônios , Ocitocina , Aprendizado Social , Animais , Camundongos , Agressão/fisiologia , Aprendizagem da Esquiva/fisiologia , Sinais (Psicologia) , Medo/fisiologia , Hipotálamo/citologia , Hipotálamo/metabolismo , Vias Neurais/fisiologia , Neurônios/metabolismo , Ocitocina/metabolismo , Receptores de Ocitocina/metabolismo , Comportamento Social , Aprendizado Social/fisiologia , Núcleo Supraóptico/citologia , Núcleo Supraóptico/metabolismo , Núcleo Hipotalâmico Ventromedial/citologia , Núcleo Hipotalâmico Ventromedial/metabolismo , Plasticidade NeuronalRESUMO
OBJECTIVE: To investigate the mechanistic basis for the anti-proliferation and anti-invasion effect of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) and celastrol combination treatment (TCCT) in glioblastoma cells. METHODS: Cell counting kit-8 was used to detect the effects of different concentrations of celastrol (0-16 µmol/L) and TRAIL (0-500 ng/mL) on the cell viability of glioblastoma cells. U87 cells were randomly divided into 4 groups, namely control, TRAIL (TRAIL 100 ng/mL), Cel (celastrol 0.5 µmol/L) and TCCT (TRAIL 100 ng/mL+ celastrol 0.5 µmol/L). Cell proliferation, migration, and invasion were detected by colony formation, wound healing, and Transwell assays, respectively. Quantitative reverse transcription polymerase chain reaction and Western blotting were performed to assess the levels of epithelial-mesenchymal transition (EMT) markers (zona occludens, N-cadherin, vimentin, zinc finger E-box-binding homeobox, Slug, and ß-catenin). Wnt pathway was activated by lithium chloride (LiCl, 20 mol/L) and the mechanism for action of TCCT was explored. RESULTS: Celastrol and TRAIL synergistically inhibited the proliferation, migration, invasion, and EMT of U87 cells (P<0.01). TCCT up-regulated the expression of GSK-3ß and down-regulated the expression of ß-catenin and its associated proteins (P<0.05 or P<0.01), including c-Myc, Cyclin-D1, and matrix metalloproteinase (MMP)-2. In addition, LiCl, an activator of the Wnt signaling pathway, restored the inhibitory effects of TCCT on the expression of ß-catenin and its downstream genes, as well as the migration and invasion of glioblastoma cells (P<0.05 or P<0.01). CONCLUSIONS: Celastrol and TRAIL can synergistically suppress glioblastoma cell migration, invasion, and EMT, potentially through inhibition of Wnt/ß-catenin pathway. This underlies a novel mechanism of action for TCCT as an effective therapy for glioblastoma.
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Glioblastoma , Triterpenos Pentacíclicos , Via de Sinalização Wnt , Humanos , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , beta Catenina/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Ligantes , Linhagem Celular Tumoral , Apoptose , Fatores de Necrose Tumoral/farmacologia , Proliferação de Células , Movimento Celular , Transição Epitelial-MesenquimalRESUMO
Objective To investigate the efficacy of Dingxuan Decoction combined with vestibular function rehabilitation training in the treatment of Meniere's disease and to observe its effect on clinical symptoms and blood flow of vertebral artery.Methods A total of 100 patients with Meniere's disease of liver-kidney yin deficiency complicated with wind-water upward stirring type were randomly divided into an observation group and a control group,with 50 patients in each group.The control group was given conventional treatment and vestibular function rehabilitation training,and the observation group was treated with Dingxuan Decoction on the basis of treatment for the control group.The two groups were treated for 4 weeks and then were followed up for 6 months.The changes of traditional Chinese medicine(TCM)syndrome score,Dizziness Handicap Inventory(DHI)score,Tinnitus Handicap Inventory(THI)score,hearing visual analogue scale(VAS)score and vertebral artery blood flow in the two groups were observed before and after the treatment.After treatment,the TCM syndrome efficacy,hearing improvement and follow-up results were compared between the two groups.Results(1)After 4 weeks of treatment,the total effective rate for TCM syndrome efficacy of the observation group was 86.00%(43/50),and that of the control group was 62.00%(31/50),and the intergroup comparison showed that the TCM syndrome efficacy in the observation group was significantly superior to that in the control group(P<0.01).(2)After 4 weeks of treatment,the hearing of patients in both groups was improved,and the total effective rate for the efficacy of hearing improvement in the observation group was 76.00%(38/50),while that in the control group was 46.00%(23/50).The intergroup comparison showed that the efficacy of hearing improvement in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the TCM syndrome scores,DHI score,THI score and hearing VAS scores in the two groups were all decreased compared with those before treatment(P<0.05 or P<0.01),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(4)After treatment,the average blood flow velocity of the left vertebral artery(LVA)and the right vertebral artery(RVA)in the two groups were both increased compared with those before treatment(P<0.05),and the increase in the observation group was significantly superior to that in the control group(P<0.05 or P<0.01).(5)The results of 6-month follow-up after treatment showed that the incidence of Meniere's disease and the frequency of attack in the observation group were significantly reduced compared with those in the control group,and the episode duration in the observation group was significantly shorter than that in the control group,the differences being all statistically significant(P<0.05 or P<0.01).Conclusion Dingxuan Decoction combined with vestibular function rehabilitation training exert certain effect in treating patients with Meniere's disease of liver-kidney yin deficiency complicated with wind-water upward stirring type,and the therapy is effective on improving patients'clinical symptoms and vertebral artery blood flow,reducing the risk of recurrence and improving the quality of life of the patients.
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Objective To observe the clinical efficacy of acupuncture combined with rehabilitation training in treating qi deficiency and blood stasis type of hypertensive cerebral hemorrhage in the recovery stage.Methods A total of 132 patients with qi deficiency and blood stasis type of hypertensive cerebral hemorrhage in the recovery period were randomly divided into observation group and control group,with 66 cases in each group,the control group was given western medicine conventional treatment combined with rehabilitation training,and the observation group was treated with acupuncture on the basis of the control group.Both groups of patients were treated for 12 consecutive weeks.After 12 weeks of treatment,the clinical efficacy of the two groups was evaluated.The changes of simplified Fugl-Meyer Assessment(FMA),National Institutes of Health Neurological Impairment Scale(NIHSS),and traditional Chinese medicine(TCM)syndrome scores,as well as the changes of serum interleukin 6(IL-6),homocysteine(Hcy),and endothelin 1(ET-1),serum matrix metalloproteinase 9(MMP-9),and brain-derived neurotrophic factor(BDNF)levels were observed before and after the treatment of the patients in the two groups.The changes of serum serine-threonine protein kinase(AKT),phosphatidylinositol-3 kinase(PI3K),and Bcl-2-related X protein(bax)levels were compared between the two groups before and after treatment.Results(1)After treatment,the serum IL-6,Hcy,ET-1 levels of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the serum IL-6,Hcy,ET-1 levels,and the difference was statistically significant(P<0.05).(2)After treatment,the serum MMP-9 and BDNF levels of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving serum MMP-9 and BDNF levels,with statistically significant differences(P<0.05).(3)After treatment,the serum AKT,PI3K,bax levels of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving serum AKT,PI3K,bax levels,and the difference was statistically significant(P<0.05).(4)After treatment,the FMA score,TCM syndrome scores,and NIHSS score of patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the FMA score,TCM syndrome scores,and NIHSS score,and the differences were statistically significant(P<0.05).(5)The total effective rate was 93.34%(62/66)in the observation group and 81.82%(54/66)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P<0.05).Conclusion Acupuncture combined with rehabilitation training for the treatment of patients recovering from hypertensive cerebral hemorrhage of qi deficiency and blood stasis type can significantly reduce the patient's inflammatory response,regulate the level of neurofactors,inhibit neuronal apoptosis,and promote the recovery of neurological function,and the clinical efficacy is remarkable.
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Depressive disorder is a severe and complex mental illness. There are a few anti-depressive medications that can reduce depressive symptoms, but with adverse or side effects. GaoYou-13 (GY-13), commonly known as Areca Thirteen Pill, is a traditional medicine for depression treatment with significant clinical impact. However, the molecular mechanism of GY-13 has not been fully elucidated. This study aimed to explore and explain the action and mechanism of GY-13 in treatment for depression. SD male rats were stimulated differently daily for 42 days to construct a depression rat model and divided into six groups: the control, CUMS model, GY-13L, GY-13 M, GY-13H, and FLUO. The body weight of was measured on day 7, 14, 21, 28, 35, and 42 or different days, and the behavioral tests (Open-field test, Sucrose preference test, Morris water maze) were made alongside. After the rats were decapitated, the rat brains were stained with Nissl or H&E dyes. The serums of TNF-α and IL-1ß were tested. The protein of p-IKKα, p-IкBα, and p-NFкBp65 was traced. Then nano-LC-MS/MS analysis was made to detect the mechanism of GY-13. The active ingredients, drug targets, and key pathways of GY-13 in treating depression were analyzed through network pharmacology and molecular docking. With immunohistochemistry, quantitative RT-PCR, and western-blot techniques, the therapeutic mechanism of GY-13 was traced and analyzed. This study revealed that GY-13 significantly enhances autonomous and exploratory behavior, sucrose consumption, learning and memory ability, and hippocampal neuronal degeneration, which inhibits inflammation. In addition, omics analysis showed several proteins were altered in the hippocampus of rats following CUMS and GY-13 treatment. Bioinformatics analysis and network pharmacology revealed the antidepressant effects of GY-13 are related to the chemokine/chemokine receptor axis. Immunohistochemistry, western blotting and RT-PCR assay further support the findings of omics analysis. We highlighted the importance of the chemokine/chemokine receptor axis in the treatment of depression, as well as showed GY-13 can be used as a novel targeted therapy for depression treatment.
Assuntos
Quimiocinas , Depressão , Ratos Sprague-Dawley , Animais , Masculino , Depressão/tratamento farmacológico , Quimiocinas/metabolismo , Ratos , Medicamentos de Ervas Chinesas/farmacologia , Simulação de Acoplamento Molecular , Comportamento Animal/efeitos dos fármacos , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacosRESUMO
This study conducted pairwise and network meta-analysis to evaluate the effectiveness of three mind-body exercise interventions (Tai Chi, Qigong, and yoga) on physical capacity, psychological well-being, and quality of life in stroke patients. The research encompassed 30 studies involving 2107 participants and utilized the Risk of Bias 2.0 tool for quality assessment. Pairwise analysis revealed that all three mind-body exercises significantly enhanced patients' quality of life. Tai Chi demonstrated the most comprehensive improvements in balance, limb motor function, activities of daily living, and depression. Network meta-analysis indicated that Qigong was the most effective in improving balance and quality of life for post-stroke patients, followed by Tai Chi. These findings underscore the positive impact of mind-body exercises on both physical and psychosocial outcomes in stroke patients. However, further research involving rigorously designed and adequately powered trials is necessary to enhance the level of evidence in this area.