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1.
Transl Lung Cancer Res ; 13(1): 76-94, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38405005

RESUMO

Background: Black race is associated with advanced stage at diagnosis and increased mortality in non-small cell lung cancer (NSCLC). Most studies focus on race alone, without accounting for social determinants of health (SDOH). We explored the hypothesis that racial disparities in stage at diagnosis and outcomes are associated with SDOH and influence treatment decisions by patients and providers. Methods: Patients with NSCLC newly diagnosed at Indiana University Simon Comprehensive Cancer Center (IUSCCC) from January 1, 2000 to May 31, 2015 were studied. Multivariable regression analyses were conducted to examine the impact of SDOH (race, gender, insurance status, and marital status) on diagnosis stage, time to treatment, receipt of and reasons for not receiving guideline concordant treatment, and 5-year overall survival (OS) based on Kaplan-Meier curves. Results: A total of 3,349 subjects were included in the study, 12.2% of Black race. Those diagnosed with advanced-stage NSCLC had a significantly higher odds of being male, uninsured, and Black. Five-year OS was lower in those of Black race, male, single, uninsured, Medicare/Medicaid insurance, and advanced stage. Adjusted for multiple variables, individuals with Medicare, Medicare/Medicaid, uninsured, widowed, and advanced stage at diagnosis, were associated with significantly lower OS time. Black, single, widowed, and uninsured individuals were less likely to receive stage appropriate treatment for advanced disease. Those uninsured [odds ratio (OR): 3.876, P<0.001], Medicaid insurance (OR: 3.039, P=0.0017), and of Black race (OR: 1.779, P=0.0377) were less likely to receive curative-intent surgery for early-stage NSCLC because it was not a recommended treatment. Conclusions: We found racial, gender, and socioeconomic disparities in NSCLC diagnosis stage, receipt of stage-appropriate treatment, and reasons for guideline discordance in receipt of curative intent surgery for early-stage NSCLC. While insurance type and marital status were associated with worse OS, race alone was not. This suggests racial differences in outcomes may not be associated with race alone, but rather worse SDOH disproportionately affecting Black individuals. Efforts to understand advanced diagnosis and reasons for failure to receive stage-appropriate treatment by vulnerable populations is needed to ensure equitable NSCLC care.

2.
Zhongguo Zhong Yao Za Zhi ; 49(1): 1-14, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403333

RESUMO

Polycystic ovary syndrome(PCOS) is a highly prevalent endocrine and reproductive disorder characterized by ovulatory dysfunction, hyperandrogenism(HA), and polycystic ovarian morphology(PCOM). It is often accompanied by insulin resistance(IR), obesity, and metabolic disorders and can lead to cardiovascular diseases, endometrial carcinoma and many other late complications, seriously affecting the physical and mental health and quality of life in premenopausal women. The etiology of PCOS is still unknown and many scholars assume that mitochondrial dysfunction may represent a major pathogenic factor in PCOS in recent years. With a holistic view, treatment based on syndrome differentiation, and multi-system and multi-target treatment manner, traditional Chinese medicine(TCM) can mitigate the symptoms and signs of PCOS from multiple aspects. Although there have been reviews on the mechanism of mitochondrial dysfunction in PCOS, there is still a lack of reviews on the intervention of mitochondrial function by TCM to treat PCOS. Therefore, this paper focuses on the role of mitochondrial dysfunction in PCOS and summarizes the studies about the TCM intervention of PCOS by regulating the mitochondrial function, inflammation, oxidative stress(OS), autophagy, and apoptosis in the last five years, aiming to shed new light on the prevention and treatment of PCOS with TCM.


Assuntos
Medicina Tradicional Chinesa , Doenças Mitocondriais , Síndrome do Ovário Policístico , Feminino , Humanos , Doenças Mitocondriais/complicações , Doenças Mitocondriais/terapia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/terapia
3.
Phytomedicine ; 126: 155470, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38417242

RESUMO

BACKGROUND: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity. PURPOSE: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis. METHODS: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma. RESULTS: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress. CONCLUSIONS: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment.


Assuntos
Asma , Ácido Rosmarínico , Humanos , Imunidade Inata , RNA Ribossômico 16S/genética , Lipopolissacarídeos , Serotonina , Linfócitos , Asma/tratamento farmacológico , Asma/metabolismo , Pulmão/metabolismo , Ácidos Graxos Voláteis/metabolismo
4.
Bioact Mater ; 33: 532-544, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38162511

RESUMO

The clinical application of cancer immunotherapy is unsatisfied due to low response rates and systemic immune-related adverse events. Microwave hyperthermia can be used as a synergistic immunotherapy to amplify the antitumor effect. Herein, we designed a Gd-based metal-organic framework (Gd-MOF) nanosystem for MRI-guided thermotherapy and synergistic immunotherapy, which featured high performance in drug loading and tumor tissue penetration. The PD-1 inhibitor (aPD-1) was initially loaded in the porous Gd-MOF (Gd/M) nanosystem. Then, the phase change material (PCM) and the cancer cell membrane were further sequentially modified on the surface of Gd/MP to obtain Gd-MOF@aPD-1@CM (Gd/MPC). When entering the tumor microenvironment (TME), Gd/MPC induces immunogenic death of tumor cells through microwave thermal responsiveness, improves tumor suppressive immune microenvironment and further enhances anti-tumor ability of T cells by releasing aPD-1. Meanwhile, Gd/MPC can be used for contrast-enhanced MRI. Transcriptomics data revealed that the downregulation of MSK2 in cancer cells leads to the downregulation of c-fos and c-jun, and ultimately leads to the apoptosis of cancer cells after treatment. In general, Gd/MPC nanosystem not only solves the problem of system side effect, but also achieves the controlled drug release via PCM, providing a promising theranostic nanoplatform for development of cancer combination immunotherapy.

5.
Neurobiol Dis ; 190: 106372, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38061397

RESUMO

Gait disturbance is a manifestation of cerebral small vessel disease (CSVD). The posterolateral thalamus (PL), whose blood is mainly supplied by the P2 segment of posterior cerebral artery (P2-PCA), plays pivotal roles in gait regulation. We investigated the influence of the distance between P2-PCA and PL on gait with varying CSVD burden. 71 participants were divided into low and high CSVD burden groups. The distance from P2-PCA to PL was measured using 7 T TOF-MRA and categorized into an immediate or distant PCA-to-thalamus pattern. Functional connectivity (FC) and voxel-based morphometry were assessed to evaluate functional and structural alterations. In the low CSVD burden group, immediate PCA-to-thalamus supply strongly correlates with longer step length and higher wave phase time percent, and exhibited enhanced FCs in left supplementary motor area, right precentral cortex (PreCG.R). While in the high CSVD burden group, no association between PCA-to-thalamus pattern and gait was found, and we observed reduced FC in PreCG.R with immediate PCA-to-thalamus pattern. Higher CSVD burden was associated with decreased gray matter density in bilateral thalamus. However, no significant structural thalamic change was observed between the two types of PCA-to-thalamus patterns in all patients. Our study demonstrated patients with immediate PCA-to-thalamus supply exhibited better gait performance in low CSVD burden populations, which also correlated with enhanced FCs in motor-related cortex, indicating the beneficial effects of the immediate PCA-to-thalamus supply pattern. In the higher burden CSVD populations, the effects of PCA-to-thalamus pattern on gait are void, attributable to the CSVD-related thalamic destruction and impairment of thalamus-related FC.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Artéria Cerebral Posterior , Humanos , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Substância Cinzenta , Imageamento por Ressonância Magnética , Tálamo/diagnóstico por imagem
7.
PeerJ ; 11: e16386, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38025755

RESUMO

This study aimed to examine the impact of nitrogen (N) fertilization on phyllosphere microorganisms in silage maize (Zea mays) to enhance the production of high-quality silage. The effects of different N application rates (160, 240, and 320 kg ha-1) and maturity stages (flowering and dough stages) on microbial diversity, abundance and physiochemical properties of the leaf surfaces were evaluated in a field experiment. The results showed that N application rates did not significantly impact the abundance of lactic acid bacteria (LAB), aerobic bacteria (AB), yeasts, or molds on the leaf surfaces. However, these microbes were more abundant during the flowering stage compared to the dough stage. Furthermore, the N application rate had no significant impact on inorganic phosphorus, soluble sugar, free amino acids, total phenolic content, and soluble protein concentrations, or pH levels on the leaf surfaces. Notably, these chemical indices were lower during the dough stage. The abundance of Pantoea decreased with higher N application rates, while that of other microorganisms did not changes significantly. The abundance of AB, LAB, yeasts, and molds were positively correlated with soluble sugar, soluble protein, inorganic phosphorus, free amino acids, and total phenolic concentrations on leaf surfaces. Moreover, water loss was negatively correlated with the abundance of AB, LAB, yeasts, and molds, whereas water retention capacity and stomatal density were positively correlated with microbial abundance. We recommend applying an optimal N rate of 160 kg ha-1 to silage maize and harvesting at the flowering stage is recommended.


Assuntos
Microbiota , Silagem , Silagem/análise , Zea mays/metabolismo , Nitrogênio/farmacologia , Folhas de Planta , Carboidratos , Fungos , Leveduras , Açúcares/metabolismo , Aminoácidos/metabolismo , Fósforo/metabolismo , Água/metabolismo
8.
Int J Biol Macromol ; 247: 125843, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37460073

RESUMO

Ginseng is widely regarded as a panacea in Oriental medicine mainly due to its immunomodulatory activity. We previously found that sulfur fumigation, a commonly used pesticidal and anti-bacterial processing practice, weakened the immunomodulatory activity of ginseng. However, if and how sulfur fumigation affects the polysaccharides in ginseng, the crucial components contributing to the immunomodulatory function, remain unknown. Here we report that polysaccharides extracted from sulfur-fumigated ginseng (SGP) presented different chemical properties with polysaccharides extracted with non-fumigated ginseng (NGP), particularly increased water extraction yield and decreased branching degree. SGP had weaker immunomodulatory activity than NGP in immunocompromised mice, as evidenced by less improved immunophenotypes involving body weight, immune organ indexes, white blood cells, lymphocyte cell populations and inflammation. The different immunomodulatory activities were accompanied by changes in the interaction between the polysaccharides and gut microbiota, in which SGP stimulated the growth of different bacteria but produced less SCFAs as compared to NGP. Fecal microbiota transplantation experiment suggested that gut microbiota played a central role in causing the weakened immunomodulatory activity in vivo. This study provides definite evidence that sulfur fumigation affects the chemistry and bioactivity of ginseng polysaccharides, thereby contributing to understanding how sulfur fumigation weakens the immunomodulatory activity of ginseng.


Assuntos
Panax , Camundongos , Animais , Panax/química , Fumigação , Enxofre/química , Polissacarídeos/farmacologia , Extratos Vegetais
9.
Drug Des Devel Ther ; 17: 1763-1782, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333964

RESUMO

Purpose: Gandouling Tablets (GDL), a proprietary Chinese medicine, have shown a preventive effect against Wilson's disease (WD)-induced neuronal damage in previous studies. However, the potential mechanisms need additional investigation. Combining metabonomics and network pharmacology revealed the GDL pathway against WD-induced neuronal damage. Methods: The WD rat model with a high copper load was developed, and nerve damage was assessed. Total metabonomics was used to identify distinct hippocampus metabolites and enriched metabolic pathways in MetaboAnalyst. The GDL's possible targets against WD neuron damage were then determined by network pharmacology. Cytoscape constructed compound metabonomics and pharmacology networks. Moreover, molecular docking and Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) validated key targets. Results: GDL reduced WD-induced neuronal injury. Twenty-nine GDL-induced metabolites may protect against WD neuron injury. According to network pharmacology, we identified three essential gene clusters, of which genes in cluster 2 had the most significant impact on the metabolic pathway. A comprehensive investigation identified six crucial targets, including UGT1A1, CYP3A4, CYP2E1, CYP1A2, PIK3CB, and LPL, and their associated core metabolites and processes. Four targets reacted strongly with GDL active components. GDL therapy improved five targets' expression. Conclusion: This collaborative effort revealed the mechanisms of GDL against WD neuron damage and a way to investigate the potential pharmacological mechanisms of other Traditional Chinese Medicine (TCM).


Assuntos
Medicamentos de Ervas Chinesas , Degeneração Hepatolenticular , Ratos , Animais , Degeneração Hepatolenticular/tratamento farmacológico , Degeneração Hepatolenticular/genética , Degeneração Hepatolenticular/metabolismo , Cobre/metabolismo , Cobre/uso terapêutico , Farmacologia em Rede , Simulação de Acoplamento Molecular , Metabolômica , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico
10.
Biomed Pharmacother ; 163: 114754, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37094549

RESUMO

Metformin (MTF) and berberine (BBR) share several therapeutic benefits in treating metabolic-related disorders. However, as the two agents have very different chemical structure and bioavailability in oral route, the goal of this study is to learn their characteristics in treating metabolic disorders. The therapeutic efficacy of BBR and MTF was systemically investigated in the high fat diet feeding hamsters and/or ApoE(-/-) mice; in parallel, gut microbiota related mechanisms were studied for both agents. We discovered that, although both two drugs had almost identical effects on reducing fatty liver, inflammation and atherosclerosis, BBR appeared to be superior over MTF in alleviating hyperlipidemia and obesity, but MTF was more effective than BBR for the control of blood glucose. Association analysis revealed that the modulation of intestinal microenvironment played a crucial role in the pharmacodynamics of both drugs, in which their respective superiority on the regulation of gut microbiota composition and intestinal bile acids might contribute to their own merits on lowering glucose or lipids. This study shows that BBR may be a good alternative for MTF in treating diabetic patients, especially for those complicated with dyslipidemia and obesity.


Assuntos
Berberina , Hiperlipidemias , Metformina , Cricetinae , Camundongos , Animais , Metformina/farmacologia , Metformina/uso terapêutico , Berberina/farmacologia , Berberina/uso terapêutico , Obesidade/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Lipídeos/uso terapêutico
11.
Zhongguo Zhong Yao Za Zhi ; 48(1): 170-182, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36725269

RESUMO

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.


Assuntos
Medicamentos de Ervas Chinesas , Fator de Necrose Tumoral alfa , Ácido Clorogênico , Medicamentos de Ervas Chinesas/farmacologia , Ácido gama-Aminobutírico , Interleucina-6 , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Fator de Necrose Tumoral alfa/genética , Animais , Camundongos , Células RAW 264.7
12.
J Ethnopharmacol ; 308: 116288, 2023 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-36809822

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis Sieb. et Zucc., is a valuable herb commonly used in Chinese medicine clinics. Loganin is a major iridoid glycoside obtained from the traditional Chinese herb Corni Fructus. Loganin, which has been shown to improve depression-like behavior in mice exposed to acute stress, is probably a potential antidepressant candidate. AIM OF THE STUDY: Loganin was evaluated for its effect on chronic unpredictable mild stress (CUMS) induced depressive-like mice, and its action mechanisms were explored. MATERIALS AND METHODS: ICR mice were subjected to the CUMS stimulation method to induce depression. The therapeutic effect of loganin on depressive-like behavior was evaluated by a series of behavioral tests such as sucrose preference test (SPT), forced swim test (FST), tail suspension test (TST) and open-field test (OFT). In addition, the serum levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were measured using ELISA. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). The levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were measured using western blot analysis. RESULTS: The results showed that CUMS induced depressive-like behaviors in mice, as indicated by behavioral tests. Administration of loganin increased the sucrose preference in SPT, as well as decreased the immobility time in FST and TST. Loganin could also improve food intake, and increased crossing times in the OFT. In mechanism, loganin restored the secretion of monoamine neurotransmitters, ACTH and CORT to normal levels. In addition, loganin elevated the expression of BDNF in the hippocampus. In conclusion, loganin exerts antidepressant-like effects in CUMS model mice through modulating monoamine neurotransmitters, ACTH, CORT and BDNF. CONCLUSION: Loganin effectively ameliorated depressive-like symptoms in CUMS-exposed mice by increasing 5-hydroxytryptamine (5-HT) and dopamine (DA) levels, alleviating hypothalamic-pituitary-adrenal (HPA) axis dysfunction, and increasing BDNF expression. In conclusion, the findings of the current study extensive evidence for the application of loganin in stress-associated disorders, specifically targeting depression.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Depressão , Camundongos , Animais , Depressão/tratamento farmacológico , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Camundongos Endogâmicos ICR , Antidepressivos/farmacologia , Hipocampo , Hormônio Adrenocorticotrópico , Sacarose/metabolismo , Estresse Psicológico/tratamento farmacológico , Modelos Animais de Doenças , Comportamento Animal
13.
Pharm Biol ; 61(1): 177-188, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36620922

RESUMO

CONTEXT: Polygonum cuspidatum Sieb. et Zucc (Polygonaceae), the root of which is included in the Chinese Pharmcopoeia under the name 'Huzhang', has a long history as a medicinal plant and vegetable. Polygonum cuspidatum has been used in traditional Chinese medicine for the treatment of inflammation, hyperlipemia, etc. OBJECTIVE: This article reviews the pharmacological action and the clinical applications of Polygonum cuspidatum and its extracts, whether in vivo or in vitro. We also summarized the main phytochemical constituents and pharmacokinetics of Polygonum cuspidatum and its extracts. METHODS: The data were retrieved from major medical databases, such as CNKI, PubMed, and SinoMed, from 2014 to 2022. Polygonum cuspidatum, pharmacology, toxicity, clinical application, and pharmacokinetics were used as keywords. RESULTS: The rhizomes, leaves, and flowers of Polygonum cuspidatum have different phytochemical constituents. The plant contains flavonoids, anthraquinones, and stilbenes. Polygonum cuspidatum and the extracts have anti-inflammatory, antioxidation, anticancer, heart protection, and other pharmacological effects. It is used in the clinics to treat dizziness, headaches, traumatic injuries, and water and fire burns. CONCLUSIONS: Polygonum cuspidatum has the potential to treat many diseases, such as arthritis, ulcerative colitis, asthma, and cardiac hypertrophy. It has a broad range of medicinal applications, but mainly focused on root medication; its aerial parts should receive more attention. Pharmacokinetics also need to be further investigated.


Assuntos
Fallopia japonica , Plantas Medicinais , Polygonum , Extratos Vegetais/uso terapêutico , Extratos Vegetais/farmacocinética , Medicina Tradicional Chinesa , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/uso terapêutico
14.
Nat Mater ; 22(2): 242-248, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36635590

RESUMO

Biointegrated neuromorphic hardware holds promise for new protocols to record/regulate signalling in biological systems. Making such artificial neural circuits successful requires minimal device/circuit complexity and ion-based operating mechanisms akin to those found in biology. Artificial spiking neurons, based on silicon-based complementary metal-oxide semiconductors or negative differential resistance device circuits, can emulate several neural features but are complicated to fabricate, not biocompatible and lack ion-/chemical-based modulation features. Here we report a biorealistic conductance-based organic electrochemical neuron (c-OECN) using a mixed ion-electron conducting ladder-type polymer with stable ion-tunable antiambipolarity. The latter is used to emulate the activation/inactivation of sodium channels and delayed activation of potassium channels of biological neurons. These c-OECNs can spike at bioplausible frequencies nearing 100 Hz, emulate most critical biological neural features, demonstrate stochastic spiking and enable neurotransmitter-/amino acid-/ion-based spiking modulation, which is then used to stimulate biological nerves in vivo. These combined features are impossible to achieve using previous technologies.


Assuntos
Elétrons , Polímeros , Neurônios/fisiologia , Transdução de Sinais , Semicondutores
15.
J Ethnopharmacol ; 306: 116158, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-36638854

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dengzhan shengmai (DZSM) formula, composed of four herbal medicines (Erigeron breviscapus, Panax ginseng, Schisandra chinensis, and Ophiopogon japonicus), is widely used in the recovery period of ischemic cerebrovascular diseases; however, the associated molecular mechanism remains unclear. AIM OF THE STUDY: The purpose of this study was to uncover the links between the microbiota-gut-brain axis and the efficacy of DZSM in ameliorating cerebral ischemic diseases. MATERIALS AND METHODS: The effects of DZSM on the gut microbiota community and bacteria-derived short-chain fatty acid (SCFA) production were evaluated in vivo using a rat model of cerebral ischemia and in vitro through the anaerobic incubation with fresh feces derived from model animals. Subsequently, the mechanism underlying the role of SCFAs in the DZSM-mediated treatment of cerebral ischemia was explored. RESULTS: We found that DZSM treatment significantly altered the composition of the gut microbiota and markedly enhanced SCFA production. The consequent increase in SCFA levels led to the upregulation of the expression of monocarboxylate transporters and facilitated the transportation of intestinal SCFAs into the brain, thereby inhibiting the apoptosis of neurocytes via the regulation of the PI3K/AKT/caspase-3 pathway. The increased intestinal SCFA levels also contributed to the repair of the 2VO-induced disruption of gut barrier integrity and inhibited the translocation of lipopolysaccharide from the intestine to the brain, thus attenuating neuroinflammation. Consequently, cerebral neuropathy and oxidative stress were significantly improved in 2VO model rats, leading to the amelioration of cerebral ischemia-induced cognitive dysfunction. Finally, fecal microbiota transplantation could reproduce the beneficial effects of DZSM on SCFA production and cerebral ischemia. CONCLUSIONS: Our findings suggested that SCFAs mediate the effects of DZSM in ameliorating cerebral ischemia via the gut microbiota-gut-brain axis.


Assuntos
Isquemia Encefálica , Microbiota , Ratos , Animais , Eixo Encéfalo-Intestino , Fosfatidilinositol 3-Quinases , Ácidos Graxos Voláteis/metabolismo , Infarto Cerebral
16.
Phytother Res ; 37(5): 1986-1996, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36609866

RESUMO

This study was designed to evaluate antiplatelet effect and therapeutic effect of ginkgo diterpene lactone meglumine injection (GDLI) in acute ischemic stroke (AIS) patients. In this randomized, double-blind, placebo-controlled trial, we randomly assigned 70 inpatients within 48 hr after the onset of AIS to combination therapy with GDLI and aspirin (GDLI at a dose of 25 mg/d for 14 days plus aspirin at a dose of 100 mg/d for 90 days) or to placebo plus aspirin in a ratio of 1:1. Platelet function, the National Institute of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were evaluated. A good outcome was defined as NIHSS scores decrease ≥5 or mRS scores decrease ≥2. Results showed that arachidonic acid induced maximum platelet aggregation rate (AA-MAR) and mean platelet volume (MPV) of the GDLI-aspirin group were much lower than that of the aspirin group (p = 0.013 and p = 0.034, respectively) after the 14-day therapy. The combination of GDLI and aspirin was superior to aspirin alone, and had significant impact on the good outcome at day 90 (ORadj 7.21 [95%CI, 1.03-50.68], p = 0.047). In summary, GDLI has antiplatelet effect and can improve the prognosis of AIS patients.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , AVC Isquêmico/tratamento farmacológico , Ginkgo biloba , Aspirina/farmacologia , Aspirina/uso terapêutico
17.
Fitoterapia ; 165: 105397, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36539068

RESUMO

Three new isoquinoline alkaloids including a morphine derivative (1), two aporphine alkaloids (2-3), together with five known alkaloids (4-8) were obtained from the extract of Dactylicapnos scandens (D.Don) Hutch. (D. scandens). Their structures and absolute configurations were elucidated by extensive spectroscopic data analysis including HRESIMS, NMR and electronic circular dichroism (ECD) and ECD calculation. Compounds 1-8 were evaluated for ATP Citrate Lyase (ACLY) inhibitory activity through an enzymatic assay. Among them, 2 and 3 showed the high ACLY inhibitory activity with an IC50 value of 10.48 ± 1.59 and 10.89 ± 4.89 µM.


Assuntos
ATP Citrato (pro-S)-Liase , Alcaloides , Alcaloides/farmacologia , Alcaloides/química , Dicroísmo Circular , Isoquinolinas/farmacologia , Isoquinolinas/química , Estrutura Molecular , Papaveraceae/química
18.
Zhen Ci Yan Jiu ; 47(12): 1123-9, 2022 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-36571230

RESUMO

OBJECTIVE: To compare the diversities in the literature characteristics of animal experiments with acupuncture and moxibustion (acu-moxibustion) published in both Chinese and English, so as to summarize the similarities and differences in the reporting content for the animal experiment research with acu-moxibustion in the journals at home and abroad. METHODS: The articles of animal experiments with acu-moxibustion published from 2016 to 2018 were searched from CNKI, Wanfang, SinoMed, PubMed and Web of Science databases. The articles were screened according to the inclusion and exclusion criteria, and the database was established by importing the essential information, e.g. title, author, journal, impact factor, country, year of publication, citation frequency, funding, disease type, as well as the number of observation indicators and charts. The diversity was initially summarized among this type of articles between China and foreign countries. RESULTS: A total of 7 515 articles of animal experiments with acu-moxibustion were retrieved and 2 458 articles were eligible in compliance with the inclusion and exclusion criteria. Of them, there were 1 827 articles in Chinese and 631 in English. (1) Among those of Chinese-version, 169 articles (9.25%) were published in Acupuncture Research, listed the first of the article publications. Regarding the impact factor of published journal, Acupuncture Research was ranked the highest (3.187). For those published in English, 78 articles (12.36%) were published in Evidence-based Complementary and Alternative Medicine, listed the top of the article publications. Gastroenterology occupied the highest in terms of the impact factor (17.373) of published journal. (2) The first authors of Chinese-version articles were all from China, distributing in 461 institutions; of which, Beijing University of Chinese Medicine occupied the top for article publications (142 articles, 7.77%). For the English articles, 16 countries were involved regarding the first authors, and the most of them were from China (523 articles, 82.88%), followed by South Korea, Brazil, the United States and Japan. (3) The frequency of citations of Chinese articles was 7.50, which was significantly higher than that of English ones (4.61). (4) The funding supported Chinese and English articles were 1 680 (91.95%) and 569 (90.17%) respectively. (5) In the aspects of disease name and animal model, 135 and 220 diseases were included in Chinese and English articles respectively. The common top 10 diseases referred to 8 categories, i.e. stroke-related diseases, arthritis, Alzheimer's disease, depression, diabetes, spinal cord injury, hypertension and obesity. (6) In terms of the number of indicators, the maximum number was 6 for Chinese-version articles, averagely 2.46, while, it was 12 for English-version ones, 4.02 in average. (7) Among the articles of Chinese-version, the maximum number of charts was 17, and 1 028 articles had 2 to 4 charts, accounting the largest proportion (56.27%). Among those of English-version, the top number of charts was 27, and 347 articles had 4 to 6 charts, occupying the largest proportion (54.99%). CONCLUSION: The number of Chinese-version articles for acu-moxibustion experiment research is much higher than that of the English ones, the authorship is led by Chinese and most of the researches are supported by funds. There is less difference in the disease types between Chinese and English articles, but the frequency citation of Chinese articles is obviously higher than that of English ones; while, the numbers of observation indicators and charts in English articles are much more than those of Chinese ones. It is suggested that the great attention has been drawn on the acu-moxibustion experiment researches published in Chinese journals, and the reports of the researches are more complete in English journals.


Assuntos
Terapia por Acupuntura , Acupuntura , Experimentação Animal , Moxibustão , Animais , Estados Unidos , Bibliometria , China
19.
Brain Behav ; 12(12): e2811, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36374520

RESUMO

BACKGROUND: Audiovisual stimulation, such as auditory stimulation, light stimulation, and audiovisual combined stimulation, as a non-invasive stimulation, which can induce gamma oscillation, has received increased attention in recent years, and it has been preliminarily applied in the clinical rehabilitation of brain dysfunctions, such as cognitive, language, motor, mood, and sleep dysfunctions. However, the exact mechanism underlying the therapeutic effect of 40-Hz audiovisual stimulation remains unclear; the clinical applications of 40-Hz audiovisual stimulation in brain dysfunctions rehabilitation still need further research. OBJECTIVE: In order to provide new insights into brain dysfunction rehabilitation, this review begins with a discussion of the mechanism underlying 40-Hz audiovisual stimulation, followed by a brief evaluation of its clinical application in the rehabilitation of brain dysfunctions. RESULTS: Currently, 40-Hz audiovisual stimulation was demonstrated to affect synaptic plasticity and modify the connection status of related brain networks in animal experiments and clinical trials. Although its promising efficacy has been shown in the treatment of cognitive, mood, and sleep impairment, research studies into its application in language and motor dysfunctions are still ongoing. CONCLUSIONS: Although 40-Hz audiovisual stimulation seems to be effective in treating cognitive, mood, and sleep disorders, its role in language and motor dysfunctions has yet to be determined.


Assuntos
Encéfalo , Eletroencefalografia , Animais , Estimulação Acústica , Encéfalo/fisiologia , Sono/fisiologia , Atenção , Estimulação Luminosa
20.
Artigo em Inglês | MEDLINE | ID: mdl-36248406

RESUMO

Polycystic ovary syndrome (PCOS) is a lifelong reproductive endocrine disease, which is the most common cause of anovular infertility. Modern medicine mainly treats infertile patients with PCOS by improving living habits, ovulation induction therapy, and assisted reproductive technology (ART), but the effect is not satisfied. Complementary alternative medicine (CAM) has conspicuous advantages in the treatment of PCOS infertility due to its good clinical efficacy, wide mechanism of action, and no obvious adverse reactions, but its safety and effectiveness in the treatment of PCOS infertility have not been proved. Based on the existing clinical and experimental studies, this paper looks for the therapeutic effect and the mechanism behind it, and explores the safety and effectiveness of its treatment in PCOS infertility, in order to provide reference for future clinical treatment and experimental research.

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