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1.
JAMA Netw Open ; 7(2): e2354937, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38335001

RESUMO

Importance: Prehypertension increases the risk of developing hypertension and other cardiovascular diseases. Early and effective intervention for patients with prehypertension is highly important. Objective: To assess the efficacy of Tai Chi vs aerobic exercise in patients with prehypertension. Design, Setting, and Participants: This prospective, single-blinded randomized clinical trial was conducted between July 25, 2019, and January 24, 2022, at 2 tertiary public hospitals in China. Participants included 342 adults aged 18 to 65 years with prehypertension, defined as systolic blood pressure (SBP) of 120 to 139 mm Hg and/or diastolic BP (DBP) of 80 to 89 mm Hg. Interventions: Participants were randomized in a 1:1 ratio to a Tai Chi group (n = 173) or an aerobic exercise group (n = 169). Both groups performed four 60-minute supervised sessions per week for 12 months. Main Outcomes and Measures: The primary outcome was SBP at 12 months obtained in the office setting. Secondary outcomes included SBP at 6 months and DBP at 6 and 12 months obtained in the office setting and 24-hour ambulatory BP at 12 months. Results: Of the 1189 patients screened, 342 (mean [SD] age, 49.3 [11.9] years; 166 men [48.5%] and 176 women [51.5%]) were randomized to 1 of 2 intervention groups: 173 to Tai Chi and 169 to aerobic exercise. At 12 months, the change in office SBP was significantly different between groups by -2.40 (95% CI, -4.39 to -0.41) mm Hg (P = .02), with a mean (SD) change of -7.01 (10.12) mm Hg in the Tai Chi group vs -4.61 (8.47) mm Hg in the aerobic exercise group. The analysis of office SBP at 6 months yielded similar results (-2.31 [95% CI, -3.94 to -0.67] mm Hg; P = .006). Additionally, 24-hour ambulatory SBP (-2.16 [95% CI, -3.84 to -0.47] mm Hg; P = .01) and nighttime ambulatory SBP (-4.08 [95% CI, -6.59 to -1.57] mm Hg; P = .002) were significantly reduced in the Tai Chi group compared with the aerobic exercise group. Conclusions and Relevance: In this study including patients with prehypertension, a 12-month Tai Chi intervention was more effective than aerobic exercise in reducing SBP. These findings suggest that Tai Chi may help promote the prevention of cardiovascular disease in populations with prehypertension. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR1900024368.


Assuntos
Pré-Hipertensão , Tai Chi Chuan , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pressão Sanguínea , Exercício Físico , Pré-Hipertensão/terapia , Estudos Prospectivos , Adolescente , Adulto Jovem , Idoso
2.
J Ethnopharmacol ; 319(Pt 3): 117331, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-37858748

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Insomnia occurs frequently in modern society, and its common symptoms include difficulty in falling asleep and decreased sleep quality and time, memory, and attention. With the advantages of having few side-effects and reduced drug-dependence, a compound traditional Chinese medicine (TCM) prescription called Huaxiang Anshen Decoction (HAD) has been widely used in clinical practice in China mainly for primary insomnia treatment. Although the effects of volatile oils from TCM herbs have been increasingly reported, volatile oils in HAD are conventionally neglected because of its preparation process and clinical usage. Therefore, exploring the anti-insomnia effects of volatile oils from HAD is of great importance. AIM OF THE STUDY: The sedative and hypnotic effects of the conventional aqueous extracts, the volatile oils from HAD, and their combinations were investigated. METHODS: The main components in HAD volatile oils (HAD-Oils), were analyzed through gas chromatography-mass spectrometry (GC-MS). The HAD volatile oil inclusion complex (HAD-OIC) was prepared with ß-cyclodextrin, and characterized. P-chlorophenylalanine (PCPA) was used to induce insomnia mice model and the test groups of HAD aqueous extract (HAD-AE), HAD-OIC and their combination (AE-OIC). An open field test was used in evaluating the mice's activities, and the levels of 5-hydroxytryptamine (5-HT) in mice sera, glutamate (Glu) in the hypothalamus, and γ-aminobutyric acid (γ-GABA) and dopamine (DA) in the brain tissues were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: A total 74 components in HAD-Oil were determined by GC/MS, and cyperenone (20.46%) and α-cyperone (10.39%) had the highest relative content. The characterization results of the physical phase showed that volatile oils were successfully encapsulated by ß-cyclodextrin and HAD-OIC was produced. The average encapsulation rates of cyperenone and α-cyperone were 79.93% and 71.96%, respectively. The results of pharmacology study showed that all the test groups increased the body weight and decreased voluntary activity when compared with the model group (P < 0.05). The HAD-AE, HAD-OIC, and AE-OIC groups increased the levels of 5-HT in the sera and DA and Glu/γ-GABA in the brains, and AE-OIC groups showed better performance than the other test groups. CONCLUSIONS: HAD-Oil exerts sedative and hypnotic effects, which are increased when it is used with HAD-AEs. This result provides a favorable experimental evidence that volatile oils should be retained for the further development of HAD.


Assuntos
Óleos Voláteis , Distúrbios do Início e da Manutenção do Sono , beta-Ciclodextrinas , Camundongos , Animais , Distúrbios do Início e da Manutenção do Sono/induzido quimicamente , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Óleos Voláteis/química , Fenclonina/farmacologia , Serotonina , Hipnóticos e Sedativos/farmacologia , Ácido gama-Aminobutírico , Dopamina
3.
Acta Biochim Pol ; 70(3): 721-727, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37724778

RESUMO

This study aimed to figure out how microRNA (miR)-411-3p's impacts on methotrexate (MTX)'s cellular uptake and cytotoxicity in acute lymphoblastic leukaemia (ALL) CEM-C1 cells by targeting Yin-yang 1 (YY1). miR-411-3p and YY1 were detected by RT-qPCR or Western blot. Intracellular MTX concentration was measured by enzyme-linked immunosorbent assay. Cell viability and apoptosis were evaluated by CCK-8, clonal formation assay, and flow cytometry. Verification of miR-411-3p and YY1's targeting link was manifested. It came out that miR-411-3p mimic or si-YY1 elevated intracellular MTX, MTX-induced cytotoxicity and apoptosis rate in CEM-C1. However, the inverse results were noticed in cells introduced with miR-411-3p inhibitor or oe-YY1. Meanwhile, it was found that cell relative luciferase activity was reduced after co-transfection of miR-411-3p mimic with YY1-WT, indicating that miR-411-3p targeted YY1. Elevation of YY1 could turn around elevating miR-411-3p's impacts on MTX's cellular uptake and cytotoxicity in CEM-C1 cells. These findings convey that miR-411-3p motivated MTX's cellular uptake and cytotoxic impacts via targeting YY1 in leukemia cells. This study is helpful for learning about the mechanisms underlying MTX responses in ALL patients.


Assuntos
MicroRNAs , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Metotrexato/farmacologia , Yin-Yang , Transporte Biológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , MicroRNAs/genética
4.
Front Cardiovasc Med ; 10: 1147740, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37564906

RESUMO

Introduction: Preventing ischemia-reperfusion injury is the main direction of myocardial infarction treatment in the convalescent stage. Some studies have suggested that saponins in Traditional Chinese medicine (TCM) preparations can protect the myocardium by various mechanisms. Our meta-analysis aims to evaluate the efficacy of TCM saponins in treating myocardial ischemia-reperfusion injury (MIRI) and to summarize the potential molecular mechanisms further. Methods: We conducted a literature search in six electronic databases [Web of Science, PubMed, Embase, Cochrane Library, Sinomed, China National Knowledge Infrastructure (CNKI)] until October 2022. Results: Seventeen eligible studies included 386 animals (254 received saponins and 132 received vehicles). The random effect model is used to calculate the combined effect. The effect size is expressed as the weighted average difference (WMD) and 95% confidence interval (CI). Compared with placebo, saponins preconditioning reduced infarct size after MIRI significantly (WMD: -3.60,95% CI: -4.45 to -2.74, P < 0.01, I2: 84.7%, P < 0.001), and significantly increased EF (WMD: 3.119, 95% CI: 2.165 to 4.082, P < 0.01, I2: 82.9%, P < 0.0 L) and FS (WMD: 3.157, 95% CI: 2.218 to 4.097, P < 0.001, I2: 81.3%, P < 0.001). Discussion: The results show that the pre-administration of saponins from TCM has a significant protective effect on MIRI in preclinical studies, which provides an application prospect for developing anti-MIRI drugs with high efficiency and low toxicity.

5.
Trials ; 23(1): 1001, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36510218

RESUMO

BACKGROUND: Compared with optimal blood pressure (BP), the prehypertension increases the risk of incident hypertension, cardiovascular (CV) events, and death. Moderate intensity of regular physical activity can reduce BP. However, aerobic exercise has some limitations. As a safe, low-impact, enjoyable, and inexpensive form of exercise that requires minimal equipment and space, Tai Chi is expected as a viable alternative to aerobic exercise. The study aimed to assess the effect of Tai Chi intervention program, compared with aerobic exercise, on the BP in prehypertension patients. METHODS: This study is a 12-month, two-center, single-blind, parallel, randomized controlled trial. Three hundred forty-two patients with prehypertension [with a systolic blood pressure (SBP) in the range of 120 mmHg to 139 mmHg and/or a diastolic blood pressure (DBP) in the range of 80 mmHg to 89 mmHg] are randomized to one of two intervention groups in a 1:1 ratio: Tai Chi or aerobic exercise. BP monitoring methods of office blood pressure, ambulatory blood pressure monitoring (ABPM), and home blood pressure monitoring (HBPM) are used at the same time to detect BP in multiple dimensions. The primary outcome is the comparison of SBP change from baseline to 12 months in Tai Chi group and SBP change from baseline to 12 months in aerobic exercise group. The secondary endpoints are as following: (1) the comparison of DBP of office blood pressure change from baseline to 12 months between Tai Chi group and aerobic exercise group, (2) the comparison of BP and the variability of BP assessed through ABPM change from baseline to 12 months between Tai Chi group and aerobic exercise group, (3) the comparison of BP assessed through HBPM change from baseline to 12 months between Tai Chi group and aerobic exercise group. DISCUSSION: This will be the first randomized controlled trial to specifically study the benefits of Tai Chi on the blood pressure control in patients with prehypertension. The successful completion of this study will help to provide evidence for whether Tai Chi is more desirable than aerobic exercise. TRIAL REGISTRATION: Trial registration number: Chinese Clinical Trial Registry, ChiCTR1900024368. Registered on 7 July 2019, http://www.chictr.org.cn/edit.aspx?pid=39478&htm=4.


Assuntos
Hipertensão , Tai Chi Chuan , Humanos , Pressão Sanguínea , Monitorização Ambulatorial da Pressão Arterial , Método Simples-Cego , Exercício Físico/fisiologia , Hipertensão/diagnóstico , Hipertensão/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
6.
Anal Methods ; 13(40): 4739-4746, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34558572

RESUMO

In this paper, a hydrophobicity-switchable deep eutectic solvent was evaluated for the first time as an efficient extractant in the effervescence-assisted dispersive liquid-liquid microextraction method combined with the solidification of floating droplets for HPLC determination of anthraquinones in fried Cassiae semen tea infusions. Prepared from choline chloride and octanoic acid, the deep eutectic solvent could be switched between hydrophobic and hydrophilic forms by pH adjustment. The dispersion of the extractant was assisted by in situ CO2 produced from the effervescence reaction between H2SO4 and Na2CO3 without using any organic solvent or auxiliary equipment. Owing to the low melting/freezing point and low density compared with water, the extractant was solidified in an ice bath for the convenience of complete separation with the sample matrix. Some important parameters, such as species, molar ratio and volume of deep eutectic solvent, species and volume of effervescent agents were optimized to achieve the best extraction efficiency. Under the optimal conditions, extraction recoveries were obtained for four anthraquinones in the range of 91.1% to 111.9%. Relative standard deviations for intraday and interday precision were less than 3.3% and 4.0%, respectively. Greenness assessment demonstrated that the proposed method was greener than other reported methods for the determination of anthraquinones.


Assuntos
Microextração em Fase Líquida , Antraquinonas , Cromatografia Líquida de Alta Pressão , Interações Hidrofóbicas e Hidrofílicas , Sêmen , Solventes , Chá
7.
Artigo em Inglês | MEDLINE | ID: mdl-34527058

RESUMO

OBJECTIVE: This study systematically evaluated the effects of Tai Chi exercise on blood pressure, body mass index (BMI), and quality of life (QOL) in patients with hypertension. A meta-analysis was performed to provide a reliable reference for clinical practice. METHODS: We searched for randomized controlled trials (RCTs) in five English databases and two Chinese databases, with the earliest data dated December 5, 2020. A quality assessment of the methods and a meta-analysis were also conducted. RESULTS: The meta-analysis of 24 studies showed that the intervention group showed better outcomes in terms of systolic blood pressure (SBP) (SMD -1.05, 95% CI -1.44 to -0.67, P ≤ 0.001; I 2 = 93.7%), diastolic blood pressure (DBP) (SMD -0.91, 95% CI -1.24 to -0.58, P ≤ 0.001; I 2 = 91.9%), and QOL (physical functioning (SMD 0.86, 95% CI 0.36 to 1.37, P=0.001; I 2 = 91.3%), role-physical (SMD 0.86, 95% CI 0.61 to 1.11, P ≤ 0.001; I 2 = 65%), general health (SMD 0.75, 95% CI 0.32 to 1.17, P=0.001; I 2 = 88.1%), bodily pain (SMD 0.65, 95% CI 0.29 to 1.00, P ≤ 0.001; I 2 = 83.1%), vitality (SMD 0.71, 95% CI 0.34 to 1.07, P ≤ 0.001; I 2 = 84.3%), social functioning (SMD 0.63, 95% CI 0.07 to 1.19, P=0.027; I 2 = 93.1%), role-emotional (SMD 0.64, 95% CI 0.22 to 1.06, P=0.003; I 2 = 88.1%), and mental health (SMD 0.73, 95% CI 0.31 to 1.16, P=0.001; I 2 = 88.2%)) compared to those of the control group. However, no significant improvements were seen in BMI of the intervention group (SMD -0.08, 95% CI -0.35 to -0.19, P=0.554; I 2 = 69.4%) compared to that of the control group. CONCLUSION: Tai Chi is an effective intervention to improve SBP and DBP in patients with essential hypertension.

8.
J Ethnopharmacol ; 277: 114197, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34004261

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Banxia Xiexin Decoction (BXD), an ancient TCM prescription originating from Treatise on Febrile Diseases (Shang Han Lun) of the Han Dynasty, has been widely used in modern clinical practice, especially for gastrointestinal diseases, including ulcerative colitis (UC). However, the modern decoction method of BXD differs from that of the original method. Thus, an exploration of the influence of the different decoction methods on the pharmacological effects is interesting and significant. AIM OF THE STUDY: This study aimed to systematically compare the pharmacological effects of extracts of BXD on TNBS induce UC rats that were prepared by different methods, the ancient method and the modern method. The findings may provide important information for the further mechanical exploration of the classical prescription, contributing to the rational application and enhancing the understanding of BXD in modern applications or scientific research. METHODS: Fifty-four SD rats were randomly divided into the following nine groups at n = 6/group: control group; model group; salicylazosulfapyridine group; BXD ancient extraction method's low-dose group (BXD-AED-L, 3.6 g BXD-AED/kg), medium-dose group (BXD-AED-M, 7.2 g BXD-AED/kg), and high-dose group (BXD-AED-H, 14.4 g BXD-AED/kg); and BXD modern extraction method's low-dose group (BXD-MED-L, 1 g BXD-MED/kg), medium-dose group (BXD-MED-M, 2 g BXD-MED/kg), and high-dose group (BXD-MED-H, 4 g BXD-MED/kg). All the groups, except the control group, were rectally injected with 70 mg/kg ethanol solution containing TNBS (2,4,6-trinitrobenzenesulfonic acid) to establish the UC models. The pharmacological evaluations including disease activity index, colon weight index, macroscopic and histological evaluation of colon damage, and inflammatory cytokine levels (IL-4, IL-10, IL-1ß, TNF-α, and IL-6)were measured. In the network pharmacology analysis, the "herbs-components-targets-disease" network was constructed and visually analyzed with which the targets with a strong correlation with UC were screened out. RESULTS: The results showed that both BXD-AED and BXD-MED might alleviate the severity of UC with different degrees according to the majority of indices that were evaluated. At similar doses, the BXD-AED groups performed better compared with the BXD-MED groups. With the assistance of the network pharmacology analysis, some key active components (quercetin, baicalein, wogonin, and baicalin) related to the anti-UC/inflammation were screened out. The contents of the components in BXD-AED were higher than those in BXD-MED. The joint results of the study indicated that BXD, an ancient TCM compound prescription, is an effective drug candidate for the modern treatment of UC.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Inflamação/tratamento farmacológico , Animais , Colite Ulcerativa/fisiopatologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/química , Inflamação/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Índice de Gravidade de Doença , Ácido Trinitrobenzenossulfônico
9.
Artigo em Inglês | MEDLINE | ID: mdl-33149757

RESUMO

Previous studies have demonstrated that calcium-/calmodulin-dependent protein kinase II (CaMKII) and calcineurin A-nuclear factor of activated T-cell (CnA-NFAT) signaling pathways play key roles in cardiac hypertrophy (CH). However, the interaction between CaMKII and CnA-NFAT signaling remains unclear. H9c2 cells were cultured and treated with angiotensin II (Ang II) with or without silenced CaMKIIδ (siCaMKII) and cyclosporine A (CsA, a calcineurin inhibitor) and subsequently treated with Wenxin Keli (WXKL). Patch clamp recording was conducted to assess L-type Ca2+ current (ICa-L), and the expression of proteins involved in signaling pathways was measured by western blotting. Myocardial cytoskeletal protein and nuclear translocation of target proteins were assessed by immunofluorescence. The results indicated that siCaMKII suppressed Ang II-induced CH, as evidenced by reduced cell surface area and ICa-L. Notably, siCaMKII inhibited Ang II-induced activation of CnA and NFATc4 nuclear transfer. Inflammatory signaling was inhibited by siCaMKII and WXKL. Interestingly, CsA inhibited CnA-NFAT pathway expression but activated CaMKII signaling. In conclusion, siCaMKII may improve CH, possibly by blocking CnA-NFAT and MyD88 signaling, and WXKL has a similar effect. These data suggest that inhibiting CaMKII, but not CnA, may be a promising approach to attenuate CH and arrhythmia progression.

10.
Biomed Pharmacother ; 130: 110503, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34321175

RESUMO

Hypertension (HTN) is an growing emerging health issue around across the world. In recent years, increasing attention has been paid to the role of dysbacteriosis in HTN and its underlying mechanism. Short-chain fatty acids (SCFAs), which are novel metabolites of intestinal flora, exert substantial regulatory effects on HTN, providing an exciting avenue for novel therapies for this disease. They function primarily by activating transmembrane G protein-coupled receptors and inhibiting histone acetylation. In this review, we discuss the mechanisms underlying the complex interaction between SCFAs and gut microbiota composition to lower blood pressure by regulating the brain-gut and kidney-gut axes, and the role of high-salt diet, immune system, oxidative stress, and inflammatory mechanism in the development of HTN. Furthermore, we also discuss the various treatment strategies for HTN, including diet, antibiotics, probiotics, fecal microflora transplantation, and traditional Chinese medicine. In conclusion, manipulation of SCFAs opens new avenues to improve treatment of HTN.


Assuntos
Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal , Hipertensão/etiologia , Hipertensão/metabolismo , Animais , Gerenciamento Clínico , Suscetibilidade a Doenças , Disbiose , Regulação da Expressão Gênica , Histonas/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Hipertensão/diagnóstico , Hipertensão/terapia , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais
11.
Front Pharmacol ; 9: 444, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29867456

RESUMO

Anthracyclines are effective agents generally used to treat solid-tumor and hematologic malignancies. The use of anthracyclines for over 40 years has improved cancer survival statistics. Nevertheless, the clinical utility of anthracyclines is limited by its dose-dependent cardiotoxicity that adversely affects 10-30% of patients. Anthracycline-induced cardiotoxicity may be classified as acute/subacute or chronic/late toxicity and leads to devastating adverse effects resulting in poor quality of life, morbidity, and premature mortality. Traditional Chinese medicine has a history of over 2,000 years, involving both unique theories and substantial experience. Several studies have investigated the potential of natural products to decrease the cardiotoxic effects of chemotherapeutic agents on healthy cells, without negatively affecting their antineoplastic activity. This article discusses the mechanism of anthracycline-induced cardiotoxicity, and summarizes traditional Chinese medicine treatment for anthracycline-induced heart failure (HF), cardiac arrhythmia, cardiomyopathy, and myocardial ischemia in recent years, in order to provide a reference for the clinical prevention and treatment of cardiac toxicity.

12.
Artigo em Inglês | MEDLINE | ID: mdl-29849718

RESUMO

To study the antitumor effect of Xihuang pill (XHP) on the number of Treg cells in the tumor microenvironment of 4T1 breast tumor-bearing mice by PI3K/AKT/AP-1 pathway, a mouse model was established. Flow cytometry (FCM) and immunohistochemistry (IHC) were used to detect the number of Treg cells in the tumor microenvironment; terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect the apoptosis of Treg cells in tumor microenvironment. Quantitative real-time PCR (RT-qPCR) was used to detect the mRNA expression of PI3K, AKT, and AP-1 in Treg cells in tumor microenvironment; immunofluorescence (IF) and Western Blot (WB) were used to detect the protein expression of PI3K, AKT, and AP-1 in Treg cells in tumor microenvironment. Compared with the naive control group, the tumor weight in XHP groups decreased significantly (P < 0.05); FCM and IHC results showed that the number of Treg cells in the tumor microenvironment decreased with the dose of XHP groups (P < 0.05); TUNEL staining showed that the number of Treg cells in tumor microenvironment increased with the dose of XHP groups (P < 0.05); RT-qPCR results showed that the mRNA expression of PI3K and AKT in Treg cells decreased with the dose of XHP groups, while RNA expression of AP-1 increased with the dose of XHP groups (P < 0.05); IF and WB results showed that the protein expression of PI3K and AKT in Treg cells decreased with the dose of XHP groups and the protein expression of AP-1 increased with the dose of XHP groups (P < 0.05). The results suggested that XHP decreased the number of Treg cells via inhibiting PI3K and AKT expression and upregulating AP-1 expression in Treg cells and then promoting the apoptosis of Treg cells. Thus, XHP could improve the immunosuppressive state of tumor microenvironment and reverse the immune escape to inhibit tumor growth.

13.
Biomed Pharmacother ; 102: 1111-1119, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29710529

RESUMO

OBJECTIVE: To determine the role of the MEKK1/SEK1/JNK1/AP-1 pathway in the action of Xihuang pill (XHP) in reducing regulatory T (Treg) cell numbers in the tumor microenvironment in a 4T1 mouse breast cancer model, and to clarify the anti-tumor mechanism of XHP in breast cancer. METHODS: We established a mouse 4T1 breast cancer model. Model mice were administered XHP for 2 weeks, and tumor tissues were then removed, weighed, sliced, and homogenized. Treg cells in the tumor microenvironment were isolated by magnetic cell sorting and analyzed by immunohistochemistry and flow cytometry. Treg cell apoptosis was detected by TdT-mediated dUTP nick end labeling. mRNA expression levels of MEKK1, SEK1, JNK1, and AP-1 in Treg cells in the tumor microenvironment were detected by quantitative real-time PCR and their protein expression levels were detected by immunofluorescence staining and western blot. RESULTS: Tumor weights were significantly lower in the XHP groups compared with the untreated control group. The overall number of Treg cells in the tumor microenvironment decreased while the number of apoptotic Treg cells increased with increasing doses of XHP. mRNA and protein expression levels of MEKK1, SEK1, JNK1, and AP-1 in Treg cells in the tumor microenvironment increased with increasing doses of XHP. CONCLUSION: XHP might promote Treg cell apoptosis in the tumor microenvironment and further inhibit the tumor growth of 4T1 mouse breast cancer. The mechanism of XHP may be related to upregulation of gene and protein expression of MEKK1, SEK1, JNK1, and AP-1 in Treg cells in the tumor microenvironment.


Assuntos
Apoptose , Medicamentos de Ervas Chinesas/uso terapêutico , Sistema de Sinalização das MAP Quinases , Neoplasias Mamárias Animais/tratamento farmacológico , Neoplasias Mamárias Animais/patologia , Linfócitos T Reguladores/patologia , Microambiente Tumoral , Regulação para Cima , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Separação Celular , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Separação Imunomagnética , Contagem de Linfócitos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Neoplasias Mamárias Animais/enzimologia , Neoplasias Mamárias Animais/imunologia , Camundongos Endogâmicos BALB C , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Linfócitos T Reguladores/efeitos dos fármacos , Fator de Transcrição AP-1/metabolismo , Carga Tumoral/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
14.
Zhonghua Xue Ye Xue Za Zhi ; 35(10): 931-5, 2014 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-25339333

RESUMO

OBJECTIVE: To investigate the effect and mechanism of high dose Vitamin B3 on granulopoiesis in normal rat. METHODS: Twenty one healthy SD rats were randomly divided into three groups: the Vitamin B3 group (Vit B3 500 mg·kg⁻¹·d⁻¹, × 7 d), the rhG-CSF group (rhG-CSF 25 µg·kg⁻¹·d⁻¹, × 7 d) and the normal saline group (2 ml/d, × 7 d). The peripheral blood cell counts were analyzed by automatic blood cell counter before (day 0) treatment, the third day (day 3) and the seventh day (day 7) after administration of drugs, respectively. The concentration of serum nicotinamide adenine dinucleotide (NAD⁺) level was measured by enzymatic cycling assay before and after drugs treatment. The expressions of G-CSF, G-CSFR, SIRT1, C/EBPα, C/EBPß, C/EBPε and NAMPT mRNA were detected by reverse transcription real-time fluorescent quantitative PCR. RESULTS: The neutrophil counts increased significantly after 7 days of Vitamin B3 and rhG-CSF treatment compared with that of control group [(1.64 ± 0.19) × 109/L, (1.88 ± 0.37)× 109/L vs (0.86 ± 0.18) × 109/L, P<0.01]; the level of serum NAD⁺ increased significantly [(0.96 ± 0.08) nmol/L, (0.65 ± 0.12) nmol/L vs (0.36 ± 0.15) nmol/L, P<0.01]; the expression of G-CSF, G-CSFR, SIRT1, C/EBPα, C/EBPε and NAMPT mRNA in bone marrow mononuclear cells were increased significantly compared with that of control group (P<0.01). CONCLUSION: High dose of Vitamin B3 may play an important role in increasing absolute neutrophil count in healthy rat under steady state, and the mechanism may be dependent on NAMPT-NAD⁺-SIRT1 signaling pathways.


Assuntos
Neutrófilos/efeitos dos fármacos , Niacinamida/farmacologia , Animais , Células da Medula Óssea , Fator Estimulador de Colônias de Granulócitos , Contagem de Leucócitos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes
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