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1.
Complement Ther Clin Pract ; 50: 101675, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36436262

RESUMO

PURPOSE: Exercise training is an efficient non-pharmacological intervention for patients with heart failure (HF). This study aimed to objectively evaluate the effects of Baduanjin exercise on the quality of life (QOL) and exercise capacity in patients with HF. METHODS: PubMed, Embase, the Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), and Wanfang data were searched from the date of their inception until 30 September 2022. All randomised controlled trials (RCTs) evaluating the effects of Baduanjin exercise on QOL and exercise capacity in patients with HF were selected. The primary outcomes were QOL, assessed using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), and exercise capacity, evaluated using the 6-min walking test (6-MWT). A meta-analysis was performed by comparing the MLHFQ domain scores. Review Manager 5.3 and Stata 14.0, were used for the data analysis. RESULTS: Baduanjin exercise showed a favourable improvement of the overall QOL (mean difference = -8.25; 95% confidence interval: -13.62 to -2.89; P = 0.003) and exercise capacity (mean difference = 118.49; 95% confidence interval: 52.57 to 184.41; P = 0.0004). Meta-analyses of the MLHFQ domain score indicated that Baduanjin exercise significantly improved the patients' physical (mean difference = -2.83; 95% confidence interval: -3.76, -1.90; P < 0.00001), emotional (mean difference = -2.52; 95% confidence interval: -3.67 to -1.37; P < 0.0001), and general QOL (mean difference = -2.61; 95% confidence interval: -5.17 to -0.06; P = 0.05), based on the decrease in the MLHFQ domain score. Marked statistical heterogeneity (I2> 70%) was observed for all the QOL and exercise capacity outcomes. CONCLUSIONS: Baduanjin exercise is a safe, feasible, and acceptable intervention that can improve the QOL and exercise capacity in patients with HF. However, more RCTs with rigorous research designs are needed to assist in the rehabilitation of such patients.


Assuntos
Tolerância ao Exercício , Insuficiência Cardíaca , Humanos , Terapia por Exercício , Insuficiência Cardíaca/psicologia , Insuficiência Cardíaca/reabilitação , Qualidade de Vida , Exercício Físico
2.
World J Clin Cases ; 10(6): 1826-1833, 2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35317141

RESUMO

BACKGROUND: Leukemia is a broad term for blood cell cancer. Leukemia is divided into acute or chronic, depending on cell differentiation. Leukemia patients are prone to adverse reactions during chemotherapy, such as anxiety, depression, and even suicide, affecting prognosis. As a nursing model developed by three well-known cognitive psychologists, empathetic nursing with mindfulness cognitive therapy (ENMCT) can effectively reduce anxiety and depression and improve the quality of life in patients with chronic disease. AIM: To explore the effect of ENMCT on cancer-induced fatigue, hope level, and negative emotions in patients with long-term leukemia chemotherapy. METHODS: A total of 103 patients with long-term leukemia chemotherapy diagnosed and treated in our hospital from July 2017 to October 2019 were enrolled and randomly assigned to observation and control groups using the random number table approach. Fifty-one patients in the control group received routine nursing, while 52 patients in the observation group received empathic nursing with mindfulness cognitive therapy. After three months of nursing care, cancer-induced fatigue was measured with the Piper Fatigue Scale (PFS), hope level with the Herth Hope Index (HHI), and negative emotion with the Hamilton Anxiety Scale (HAMA)/Hamilton Depression Scale (HAMD). Self-management (Chinese Strategies Used by People to Promote Health) was also recorded. RESULTS: The observation group's total scores in behavior, cognition, emotion, feeling, and PFS were lower than the control group after the intervention (P < 0.05). Keeping close contact with others, the attitude of taking positive actions, the attitude toward reality and future, and the total HHI score were higher in the observation group than the control group (P < 0.05). The observation group's HAMA and HAMD scores were lower than the control group (P < 0.05). The observation group's positive attitude, self-decision, and self-relief scores were greater than the control group (P < 0.05). CONCLUSION: Empathetic nursing with cognitive mindfulness therapy is beneficial in improving cancer-related fatigue, negative emotions, expectation level, and self-management ability in patients with long-term leukemia chemotherapy.

3.
Zhongguo Zhong Yao Za Zhi ; 47(23): 6438-6449, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36604890

RESUMO

Colquhounia Root Tablets, prepared from Tripterygium, is effective for rheumatoid arthritis, diabetic nephropathy, and membranous nephropathy. However, the adverse reactions, such as liver injury, nausea, and vomiting, limit its application. This study aims to evaluate the advantages and risk of Colquhounia Root Tablets and its key active components in the treatment of rheumatoid arthritis, diabetic nephropathy, and membranous nephropathy and explore the potential mechanism in treating different diseases based on in vitro efficacy and toxicity assessment and biomolecular network analysis. First, the components of Colquhounia Root Tablets absorbed in blood were detected via ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry, and the influence of Colquhounia Root Tablets and its key components triptolide and celastrol on viability of human hepatocyte L02, human rheumatoid fibroblast-like synovial cell MH7 A, human renal tubular epithelial cell HK-2, and mouse podocyte MPC-5 was detected by cell counting kit 8(CCK8) assay. Then the expression of inflammatory cytokines of MH7 A and HK-2 cells was detected by enzyme-linked immunosorbent assay(ELISA). Moreover, the expression of nephrin and podocin in MPC-5 cells was measured by Western blot, and the expression of cytoskeletal protein by immunofluorence assay. Candidate targets of components from Colquhounia Root Tablets absorbed in blood were retrieved from TCMIP v2.0, and targets of the three diseases from GEO. The "disease-related genes-drug targets" network was constructed based on STRING, followed by pathway enrichment. Finally, molecular docking was performed by AutoDock Vina to explore the binding affinity of triptolide and celastrol with putative targets in the key signaling pathway. RESULTS:: showed that Colquhounia Root Tablets, triptolide, and celastrol can obviously reduce the levels of inflammatory cytokines in supernatant of MH7 A and HK-2 cells and enhance the expression of nephrin and podocin in MPC-5 cells. In addition, triptolide had the strongest toxicity to L02 cells, while Huobahuagen Tablets had the least toxicity to hepatocytes. Network analysis revealed that Colquhounia Root Tablets may intervene the three diseases through PI3 K/HIF1α/NOS signaling pathway. Both triptolide and celastrol had high binding affinities to corresponding targets in this signaling pathway. In conclusion, Colquhounia Root Tablets exerts similar effects on rheumatoid arthritis, diabetic nephropathy, and membranous nephropathy to triptolide and celastrol, but the toxicity was lower. PI3 K/HIF1α/NOS signaling pathway may be the common pathway of Colquhounia Root Tablets in the treatment of the three diseases.


Assuntos
Artrite Reumatoide , Nefropatias Diabéticas , Medicamentos de Ervas Chinesas , Glomerulonefrite Membranosa , Humanos , Animais , Camundongos , Simulação de Acoplamento Molecular , Citocinas , Artrite Reumatoide/tratamento farmacológico , Comprimidos , Medicamentos de Ervas Chinesas/uso terapêutico
4.
Zhongguo Zhen Jiu ; 41(8): 906-12, 2021 Aug 12.
Artigo em Chinês | MEDLINE | ID: mdl-34369703

RESUMO

OBJECTIVE: To observe the changes of functional connectivity of brain pain-emotion regulation region in patients with cervical spondylosis of cervical type by functional magnetic resonance imaging (fMRI). METHODS: Thirty-two subjects were selected. Of them, 16 patients with cervical spondylosis of cervical type were divided into an observation group and 16 healthy subjects into a control group. The patients in the observation group were treated with acupuncture at Tianzhu (BL 10), Jingbailao (EX-HN 15), Jianzhongshu (SI 15) and ashi points for 30 min. The rest-state fMRI data was collected before and after acupuncture in the observation group. The subjects in the control group received no treatment, and the rest-state fMRI data was collected once. The visual analogue scale (VAS) score before and after treatment and the pain catastrophizing scale (PCS) score before treatment in the observation group were recorded. The resting-state brain functional imaging characteristics between the observation group and control group before treatment, between the observation group before and after treatment, were compared. Based on the brain functional connectivity of region of interest (ROI) the changes of functional connectivity in insula and ventral tegmental area (VTA) in emotional regulation brain region were observed, and the correlation between functional connectivity changes and VAS、PCS scores in patients of the observation group was analyzed. RESULTS: In the observation group, the VAS score was (1.94±1.12) after the treatment, which was lower than (5.62±1.20) before treatment (P<0.05). The PCS score before treatment was (19.18±8.42) in the observation group. Compared with the control group, the areas with increased functional connectivity with insula in the observation group before acupuncture included bilateral dorsolateral prefrontal lobe and right middle cingulate gyrus, and the areas with increased functional connectivity with VTA included right central posterior gyrus and right insula. In the observation group, the connectivity coefficient of left insula and left dorsolateral prefrontal lobe (r=0.438, P<0.05), the connectivity coefficient of right insula and right dorsolateral prefrontal lobe (r=0.483, P<0.05) were positively associated with the VAS score. In the observation group, the connectivity coefficient between the right insula and the right middle cingulate gyrus (r=-0.560, P<0.05), the connectivity coefficient between the right VTA and the right insula (r=-0.525, P<0.05) were negatively associated with the PCS score. After acupuncture, the areas with decreased functional connectivity with insula included bilateral posterior central gyrus, right anterior central gyrus, middle cingulate gyrus and left corpus callosum, while the bilateral suboccipital gyrus and left cerebellum showed increased functional connectivity with right insula. The areas with decreased functional connectivity with VTA included bilateral dorsomedial prefrontal cortex, left anterior cingulate gyrus, right middle temporal gyrus and left anterior cingulate gyrus. After acupuncture in the observation group, the functional connectivity of left VTA left dorsomedial prefrontal cortex and left anterior cingulate cortex (r=-0.548, P<0.05), the functional connectivity of right VTA-bilateral dorsomedial prefrontal cortex and left anterior cingulate cortex (r=-0.547, P<0.05) were negatively associated with the PCS score. CONCLUSION: Pain involves the formation and expression of "pain-emotion-cognition". Acupuncture can systematically regulate the brain functional connections between cognitive regions such as dorsal prefrontal lobe and anterior cingulate gyrus and emotional regions such as insula and VTA in patients with cervical spondylosis of cervical type, suggesting that acupuncture has a multi-dimensional and comprehensive regulation effect on pain.


Assuntos
Terapia por Acupuntura , Espondilose , Encéfalo/diagnóstico por imagem , Emoções , Humanos , Imageamento por Ressonância Magnética , Dor , Espondilose/diagnóstico por imagem , Espondilose/terapia
5.
Artigo em Chinês | WPRIM | ID: wpr-887505

RESUMO

OBJECTIVE@#To observe the changes of functional connectivity of brain pain-emotion regulation region in patients with cervical spondylosis of cervical type by functional magnetic resonance imaging (fMRI).@*METHODS@#Thirty-two subjects were selected. Of them, 16 patients with cervical spondylosis of cervical type were divided into an observation group and 16 healthy subjects into a control group. The patients in the observation group were treated with acupuncture at Tianzhu (BL 10), Jingbailao (EX-HN 15), Jianzhongshu (SI 15) and @*RESULTS@#In the observation group, the VAS score was (1.94±1.12) after the treatment, which was lower than (5.62±1.20) before treatment (@*CONCLUSION@#Pain involves the formation and expression of "pain-emotion-cognition". Acupuncture can systematically regulate the brain functional connections between cognitive regions such as dorsal prefrontal lobe and anterior cingulate gyrus and emotional regions such as insula and VTA in patients with cervical spondylosis of cervical type, suggesting that acupuncture has a multi-dimensional and comprehensive regulation effect on pain.


Assuntos
Humanos , Terapia por Acupuntura , Encéfalo/diagnóstico por imagem , Emoções , Imageamento por Ressonância Magnética , Dor , Espondilose/terapia
6.
Food Funct ; 11(10): 8978-8986, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33001073

RESUMO

Previous researches have indicated that sleep plays a vital role in cognitive functions. Sleep deprivation (SD) causes learning and memory damage, which is associated with oxidative stress. This study was performed to investigate the neuroprotective effects of an extract of Abelmoschus manihot flower (EAM) against memory deficit induced by SD in mice. The SD model was evoked by multiple platform method for 5 days, successively. The learning and memory-improving effects of EAM were assessed by behavioral trials and the underlying mechanism was investigated by measuring the oxidative stress alteration. Our findings indicated that the SD-induced memory deficit and the EAM treatment improved the cognitive functions of mice in the object location recognition test and passive avoidance task. In addition, EAM effectively improved the activities of the antioxidant enzyme, decreased the content of malondialdehyde (MDA), and restored the protein expression of the brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB) and glutamate receptor 1 (GluR1) in brain tissues. In conclusion, EAM could improve the SD-evoked learning and memory impairments. The possible underlying mechanisms of EAM may be related to its antioxidant capacity and enhanced BDNF/TrkB/GluR1 levels in the hippocampal memory.


Assuntos
Abelmoschus/química , Transtornos da Memória/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Privação do Sono/complicações , Animais , Antioxidantes/administração & dosagem , Antioxidantes/isolamento & purificação , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cognição/efeitos dos fármacos , Flores/química , Humanos , Aprendizagem/efeitos dos fármacos , Masculino , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Memória/efeitos dos fármacos , Transtornos da Memória/etiologia , Transtornos da Memória/psicologia , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/isolamento & purificação , Proteínas Tirosina Quinases/genética , Proteínas Tirosina Quinases/metabolismo , Receptores de AMPA/genética , Receptores de AMPA/metabolismo , Privação do Sono/psicologia
7.
Phytomedicine ; 69: 153185, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32120244

RESUMO

BACKGROUND: Dihydroquercetin (DHQ) is an antifibrotic agent. However, whether DHQ can prevent renal fibrosis remains unknown. PURPOSE: This study aimed to investigate the effects of DHQ on tubulointerstitial fibrosis and its underlying mechanisms in unilateral ureteral obstruction (UUO) mice in vivo and NRK-49F cells in vitro. METHODS: In vivo, UUO mice received vehicle or DHQ treatment. In vitro, NRK-49F cells were pretreated with DHQ and exposed to transforming growth factor-ß1 (TGF-ß1). Changes in fibroblast activation, collagen synthesis, oxidative stress, and related signaling pathways were assessed by immunohistochemical staining, Western blot analysis, real-time reverse transcription-PCR, and fluorescence microscopy. RESULTS: UUO induced tubular atrophy, inflammation, fibroblast differentiation into myofibroblast, and collagen deposition, whereas DHQ ameliorated these effects. UUO also resulted in decreased levels of nuclear factor-erythroid-2-related factor 2 (Nrf2), catalase, and heme oxygenase-1, but increased H2O2 and malondialdehyde levels. DHQ treatment corrected these changes. In vitro, the intracellular Nrf2 level of NRK-49F exposed to TGF-ß1 decreased. However, DHQ rescued intracellular Nrf2 level and promoted nuclear translocation of Nrf2. DHQ scavenged TGF-ß1-induced accumulation of reactive oxygen species, inhibited TGF-ß1-induced Smad3 phosphorylation, and prevented TGF-ß1-induced fibroblast activation and collagen synthesis in NRK-49F. Nrf2 knockdown could suppress the DHQ-mediated inhibitory effects on oxidative stress, Smad3 phosphorylation, fibroblast activation, and collagen deposition. Furthermore, DHQ ameliorated established renal fibrosis in UUO mice. CONCLUSIONS: DHQ posed remarkable preventive and therapeutic effects on UUO-induced renal fibrosis and suppressed fibroblast activation by reducing oxidative stress and Smad3 phosphorylation via Nrf2 signaling. This study provided a mechanistic basis for the clinical application of DHQ in renal fibrosis treatment.


Assuntos
Nefropatias/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Substâncias Protetoras/farmacologia , Quercetina/análogos & derivados , Transdução de Sinais/efeitos dos fármacos , Animais , Fibrose , Peróxido de Hidrogênio/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/metabolismo , Nefropatias/patologia , Masculino , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Quercetina/química , Quercetina/farmacologia , Ratos , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Obstrução Ureteral/metabolismo , Obstrução Ureteral/patologia
8.
Artigo em Chinês | WPRIM | ID: wpr-873117

RESUMO

Coptidis Rhizoma-Evodia Fructus is a classic herb pair in traditional Chinese medicine prescriptions, the famous prescription is called Zuojinwan, which comes from Danxi Xinfa, is composed of Coptidis Rhizoma-Evodia Fructus (6∶1). In this formula, Coptidis Rhizoma has the effect of clearing heat and drying diuresis, purging fire to remove toxin and clearing heart. Evodia Fructus has the effects of expelling cold and alleviating pain, checking upward adverse flow of Qi tostop vomiting, and assisting yang to stop diarrhea. Coptidis Rhizoma has the properties of bitter and cold, and Evodia Fructus has the properties of pungent and calidus. Pungent drugs have divergent effects, and bitter drugs have sedimentation effect, when used in combination, they can clear the liver and purge fire, calm the adverse-rising energy and stop vomiting. On the basis of Zuojinwan, Coptidis Rhizoma-Evodia Fructus medicine has derived different compatibility ratios. Different ratios are different in terms of efficacy, usage, clinical application. Although with the application of modern analytical instruments and the development of molecular pharmacology theory, the chemical constituents and Pharmacological effects of Coptidis Rhizoma and Evodia Fructus have been fully studied, as to the principle of compatibility, and the study of pharmacological effects and chemical constituents after the compatibility of the two drugs in different proportions, there is still no comprehensive system summary. This article makes a systematic and comprehensive explanation of Coptidis Rhizoma-Evodia Fructus from the aspects of famous literature, chemical composition, pharmacological effects and clinical applicationthrough querying literature and ancient books. In order to make this herb pair more standardized, and provide reference materials for further research and development for this herb pair.

9.
Chin Med J (Engl) ; 131(19): 2287-2296, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-30246714

RESUMO

BACKGROUND: Shensong Yangxin Capsule (SSYX), traditional Chinese medicine, has been used to treat arrhythmias, angina, cardiac remodeling, cardiac fibrosis, and so on, but its effect on cardiac energy metabolism is still not clear. The objective of this study was to investigate the effects of SSYX on myocardium energy metabolism in angiotensin (Ang) II-induced cardiac hypertrophy. METHODS: We used 2 µl (10-6 mol/L) AngII to treat neonatal rat cardiomyocytes (NRCMs) for 48 h. Myocardial α-actinin staining showed that the myocardial cell volume increased. Expression of the cardiac hypertrophic marker-brain natriuretic peptide (BNP) messenger RNA (mRNA) also increased by real-time polymerase chain reaction (PCR). Therefore, it can be assumed that the model of hypertrophic cardiomyocytes was successfully constructed. Then, NRCMs were treated with 1 µl of different concentrations of SSYX (0.25, 0.5, and 1.0 µg/ml) for another 24 h. To explore the time-depend effect of SSYX on energy metabolism, 0.5 µg/ml SSYX was added into cells for 0, 6, 12, 24, and 48 h. Mitochondria was assessed by MitoTracker staining and confocal microscopy. mRNA and protein expression of mitochondrial biogenesis-related genes - Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), energy balance key factor - adenosine monophosphate-activated protein kinase (AMPK), fatty acids oxidation factor - carnitine palmitoyltransferase-1 (CPT-1), and glucose oxidation factor - glucose transporter- 4 (GLUT-4) were measured by PCR and Western blotting analysis. RESULTS: With the increase in the concentration of SSYX (from 0.25 to 1.0 µg/ml), an increased mitochondrial density in AngII-induced cardiomyocytes was found compared to that of those treated with AngII only (0.25 µg/ml, 18.3300 ± 0.8895 vs. 24.4900 ± 0.9041, t = 10.240, P < 0.0001; 0.5 µg/ml, 18.3300 ± 0.8895 vs. 25.9800 ± 0.8187, t = 12.710, P < 0.0001; and 1.0 µg/ml, 18.3300 ± 0.8895 vs. 24.2900 ± 1.3120, t = 9.902, P < 0.0001; n = 5 per dosage group). SSYX also increased the mRNA and protein expression of PGC-1α (0.25 µg/ml, 0.8892 ± 0.0848 vs. 1.0970 ± 0.0994, t = 4.319, P = 0.0013; 0.5 µg/ml, 0.8892 ± 0.0848 vs. 1.2330 ± 0.0564, t = 7.150, P < 0.0001; and 1.0 µg/ml, 0.8892 ± 0.0848 vs. 1.1640 ± 0.0755, t = 5.720, P < 0.0001; n = 5 per dosage group), AMPK (0.25 µg/ml, 0.8872 ± 0.0779 vs. 1.1500 ± 0.0507, t = 7.239, P < 0.0001; 0.5 µg/ml, 0.8872 ± 0.0779 vs. 1.2280 ± 0.0623, t = 9.379, P < 0.0001; and 1.0 µg/ml, 0.8872 ± 0.0779 vs. 1.3020 ± 0.0450, t = 11.400, P < 0.0001; n = 5 per dosage group), CPT-1 (1.0 µg/ml, 0.7348 ± 0.0594 vs. 0.9880 ± 0.0851, t = 4.994, P = 0.0007, n = 5), and GLUT-4 (0.5 µg/ml, 1.5640 ± 0.0599 vs. 1.7720 ± 0.0660, t = 3.783, P = 0.0117; 1.0 µg/ml, 1.5640 ± 0.0599 vs. 2.0490 ± 0.1280, t = 8.808, P < 0.0001; n = 5 per dosage group). The effect became more obvious with the increasing concentration of SSYX. When 0.5 µg/ml SSYX was added into cells for 0, 6, 12, 24, and 48 h, the expression of AMPK (6 h, 14.6100 ± 0.6205 vs. 16.5200 ± 0.7450, t = 3.456, P = 0.0250; 12 h, 14.6100 ± 0.6205 vs. 18.3200 ± 0.9965, t = 6.720, P < 0.0001; 24 h, 14.6100 ± 0.6205 vs. 21.8800 ± 0.8208, t = 13.160, P < 0.0001; and 48 h, 14.6100 ± 0.6205 vs. 23.7400 ± 1.0970, t = 16.530, P < 0.0001; n = 5 per dosage group), PGC-1α (12 h, 11.4700 ± 0.7252 vs. 16.9000 ± 1.0150, t = 7.910, P < 0.0001; 24 h, 11.4700 ± 0.7252 vs. 20.8800 ± 1.2340, t = 13.710, P < 0.0001; and 48 h, 11.4700 ± 0.7252 vs. 22.0300 ± 1.4180, t = 15.390; n = 5 per dosage group), CPT-1 (24 h, 15.1600 ± 1.0960 vs. 18.5800 ± 0.9049, t = 6.048, P < 0.0001, n = 5), and GLUT-4 (6 h, 10.2100 ± 0.9485 vs. 12.9700 ± 0.8221, t = 4.763, P = 0.0012; 12 h, 10.2100 ± 0.9485 vs. 16.9100 ± 0.8481, t = 11.590, P < 0.0001; 24 h, 10.2100 ± 0.9485 vs. 19.0900 ± 0.9797, t = 15.360, P < 0.0001; and 48 h, 10.2100 ± 0.9485 vs. 14.1900 ± 0.9611, t = 6.877, P < 0.0001; n = 5 per dosage group) mRNA and protein increased gradually with the prolongation of drug action time. CONCLUSIONS: SSYX could increase myocardial energy metabolism in AngII-induced cardiac hypertrophy. Therefore, SSYX might be considered to be an alternative therapeutic remedy for myocardial hypertrophy.


Assuntos
Cardiomegalia/tratamento farmacológico , Metabolismo Energético , Medicina Tradicional Chinesa , Miócitos Cardíacos/efeitos dos fármacos , Angiotensina II/metabolismo , Animais , Miocárdio , Ratos
10.
J Ethnopharmacol ; 216: 47-56, 2018 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-29366768

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Polysaccharides and small molecules commonly co-exist in decoctions of traditional Chinese medicines (TCMs). Our previous study outlined that ginseng polysaccharides (GP) could interact with co-existing ginsenosides to produce synergistic effect in an over-fatigue and acute cold stress model via gut microbiota involved mechanisms. AIM OF THE STUDY: This study aimed to verify the interactions by examining the impact of GP on oral pharmacokinetics of ginsenoside Rb1 (Rb1), the dominant protopanoxadiol (PPD)-type ginsenoside in Ginseng, on a dextran sulphate sodium (DSS) induced experimental colitis model which was characterized by gut dysbiosis, and to delineate the underlying mechanisms in vitro. MATERIALS AND METHODS: Rats received drinking water (normal group), 5% DSS (UC group), or 5% DSS plus daily oral administration of GP (GP group) for 7 days and fecal samples were collected on day -3, 0 and 6. On day 7 all animals received an oral dosage of Rb1 and blood samples were withdrawn for pharmacokinetic study. The in vitro metabolism study of Rb1 in gut microbiota from normal and UC rats and the transport study of Rb1 across Caco-2 cell monolayer were carried out in presence/absence of GP. Rb1 and its bacterial metabolites ginsenoside Rd (Rd), ginsenoside F2 (F2), Compound K (CK) and PPD were determined using LC-MS/MS. Total and target bacteria in fecal samples were determined by using 16S rRNA-based RT-PCR. ß-Glucosidase activity was determined by measuring 4-nitrophenol formed from 4-nitrophenyl-ß-D-glucopyranoside hydrolysis. RESULTS: DSS induction did not alter AUC0-t and Cmax of Rb1, which, however, were doubled together with elevated AUC0-t of the metabolites, in particular Rd and CK, in GP group. GP influenced the microbial composition and showed a prebiotic-like effect. Accordingly, GP treatment could partially restore the ß-glucosidase activity which was reduced by DSS induction. The presence of GP resulted in quicker microbial metabolism of Rb1 and higher Rd formation in first 8 h of incubation, while the impact on F2 and CK formation/conversion became obvious after 8 h. More interestingly, GP slightly stimulated Caco-2 cell growth and facilitated Rb1 transport across the Caco-2 monolayer in both directions, increasing the Papp of Rb1 from 10-7 cm/s to 10-6 cm/s. CONCLUSIONS: GP alleviated DSS-induced colitis-like symptoms and enhanced the systemic exposure of Rb1 through enhancing microbial deglycosylation and intestinal epithelial absorption of Rb1. These findings further demonstrated the important role of gut microbiota in the multifaceted action of polysaccharides in the holistic actions of traditional decoction of TCMs.


Assuntos
Anti-Inflamatórios/administração & dosagem , Bactérias/efeitos dos fármacos , Colite/tratamento farmacológico , Colo/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Ginsenosídeos/administração & dosagem , Absorção Intestinal/efeitos dos fármacos , Panax , Polissacarídeos/administração & dosagem , Administração Oral , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacocinética , Bactérias/metabolismo , Biotransformação , Células CACO-2 , Colite/induzido quimicamente , Colite/metabolismo , Colite/microbiologia , Colo/metabolismo , Colo/microbiologia , Citocinas/sangue , Sulfato de Dextrana , Modelos Animais de Doenças , Interações Medicamentosas , Disbiose , Ginsenosídeos/isolamento & purificação , Ginsenosídeos/farmacocinética , Glicosilação , Humanos , Mediadores da Inflamação/sangue , Masculino , Panax/química , Fitoterapia , Plantas Medicinais , Polissacarídeos/isolamento & purificação , Ratos Sprague-Dawley
11.
Chinese Medical Journal ; (24): 2287-2296, 2018.
Artigo em Inglês | WPRIM | ID: wpr-690223

RESUMO

<p><b>Background</b>Shensong Yangxin Capsule (SSYX), traditional Chinese medicine, has been used to treat arrhythmias, angina, cardiac remodeling, cardiac fibrosis, and so on, but its effect on cardiac energy metabolism is still not clear. The objective of this study was to investigate the effects of SSYX on myocardium energy metabolism in angiotensin (Ang) II-induced cardiac hypertrophy.</p><p><b>Methods</b>We used 2 μl (10 mol/L) AngII to treat neonatal rat cardiomyocytes (NRCMs) for 48 h. Myocardial α-actinin staining showed that the myocardial cell volume increased. Expression of the cardiac hypertrophic marker-brain natriuretic peptide (BNP) messenger RNA (mRNA) also increased by real-time polymerase chain reaction (PCR). Therefore, it can be assumed that the model of hypertrophic cardiomyocytes was successfully constructed. Then, NRCMs were treated with 1 μl of different concentrations of SSYX (0.25, 0.5, and 1.0 μg/ml) for another 24 h. To explore the time-depend effect of SSYX on energy metabolism, 0.5 μg/ml SSYX was added into cells for 0, 6, 12, 24, and 48 h. Mitochondria was assessed by MitoTracker staining and confocal microscopy. mRNA and protein expression of mitochondrial biogenesis-related genes - Peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), energy balance key factor - adenosine monophosphate-activated protein kinase (AMPK), fatty acids oxidation factor - carnitine palmitoyltransferase-1 (CPT-1), and glucose oxidation factor - glucose transporter- 4 (GLUT-4) were measured by PCR and Western blotting analysis.</p><p><b>Results</b>With the increase in the concentration of SSYX (from 0.25 to 1.0 μg/ml), an increased mitochondrial density in AngII-induced cardiomyocytes was found compared to that of those treated with AngII only (0.25 μg/ml, 18.3300 ± 0.8895 vs. 24.4900 ± 0.9041, t = 10.240, P < 0.0001; 0.5 μg/ml, 18.3300 ± 0.8895 vs. 25.9800 ± 0.8187, t = 12.710, P < 0.0001; and 1.0 μg/ml, 18.3300 ± 0.8895 vs. 24.2900 ± 1.3120, t = 9.902, P < 0.0001; n = 5 per dosage group). SSYX also increased the mRNA and protein expression of PGC-1α (0.25 μg/ml, 0.8892 ± 0.0848 vs. 1.0970 ± 0.0994, t = 4.319, P = 0.0013; 0.5 μg/ml, 0.8892 ± 0.0848 vs. 1.2330 ± 0.0564, t = 7.150, P < 0.0001; and 1.0 μg/ml, 0.8892 ± 0.0848 vs. 1.1640 ± 0.0755, t = 5.720, P < 0.0001; n = 5 per dosage group), AMPK (0.25 μg/ml, 0.8872 ± 0.0779 vs. 1.1500 ± 0.0507, t = 7.239, P < 0.0001; 0.5 μg/ml, 0.8872 ± 0.0779 vs. 1.2280 ± 0.0623, t = 9.379, P < 0.0001; and 1.0 μg/ml, 0.8872 ± 0.0779 vs. 1.3020 ± 0.0450, t = 11.400, P < 0.0001; n = 5 per dosage group), CPT-1 (1.0 μg/ml, 0.7348 ± 0.0594 vs. 0.9880 ± 0.0851, t = 4.994, P = 0.0007, n = 5), and GLUT-4 (0.5 μg/ml, 1.5640 ± 0.0599 vs. 1.7720 ± 0.0660, t = 3.783, P = 0.0117; 1.0 μg/ml, 1.5640 ± 0.0599 vs. 2.0490 ± 0.1280, t = 8.808, P < 0.0001; n = 5 per dosage group). The effect became more obvious with the increasing concentration of SSYX. When 0.5 μg/ml SSYX was added into cells for 0, 6, 12, 24, and 48 h, the expression of AMPK (6 h, 14.6100 ± 0.6205 vs. 16.5200 ± 0.7450, t = 3.456, P = 0.0250; 12 h, 14.6100 ± 0.6205 vs. 18.3200 ± 0.9965, t = 6.720, P < 0.0001; 24 h, 14.6100 ± 0.6205 vs. 21.8800 ± 0.8208, t = 13.160, P < 0.0001; and 48 h, 14.6100 ± 0.6205 vs. 23.7400 ± 1.0970, t = 16.530, P < 0.0001; n = 5 per dosage group), PGC-1α (12 h, 11.4700 ± 0.7252 vs. 16.9000 ± 1.0150, t = 7.910, P < 0.0001; 24 h, 11.4700 ± 0.7252 vs. 20.8800 ± 1.2340, t = 13.710, P < 0.0001; and 48 h, 11.4700 ± 0.7252 vs. 22.0300 ± 1.4180, t = 15.390; n = 5 per dosage group), CPT-1 (24 h, 15.1600 ± 1.0960 vs. 18.5800 ± 0.9049, t = 6.048, P < 0.0001, n = 5), and GLUT-4 (6 h, 10.2100 ± 0.9485 vs. 12.9700 ± 0.8221, t = 4.763, P = 0.0012; 12 h, 10.2100 ± 0.9485 vs. 16.9100 ± 0.8481, t = 11.590, P < 0.0001; 24 h, 10.2100 ± 0.9485 vs. 19.0900 ± 0.9797, t = 15.360, P < 0.0001; and 48 h, 10.2100 ± 0.9485 vs. 14.1900 ± 0.9611, t = 6.877, P < 0.0001; n = 5 per dosage group) mRNA and protein increased gradually with the prolongation of drug action time.</p><p><b>Conclusions</b>SSYX could increase myocardial energy metabolism in AngII-induced cardiac hypertrophy. Therefore, SSYX might be considered to be an alternative therapeutic remedy for myocardial hypertrophy.</p>


Assuntos
Animais , Ratos , Angiotensina II , Metabolismo , Cardiomegalia , Tratamento Farmacológico , Metabolismo Energético , Medicina Tradicional Chinesa , Miocárdio , Miócitos Cardíacos
12.
Chinese Journal of Nursing ; (12): 867-873, 2017.
Artigo em Chinês | WPRIM | ID: wpr-708686

RESUMO

Objective To investigate the level and influencing factors of caring behaviors perceived by elderly residents in nursing homes in Zhengzhou.Methods Totally 366 elderly residents from 20 nursing homes in Zhengzhou were investigated with a demographic data questionnaire,Short Portable Mental Status Questionnaire (SPMSQ),Barthel Index Scale (BI),and Elderly Residents-Perceived Caring Behaviors Inventory.Results The total score of caring behaviors needs was (110.99±10.09),the mean score was (3.96±0.36),the dimension score of meeting the emotion needs was the highest(4.39±0.61),the dimension score of giving confidence and hope demand was the lowest (3.56±0.58).Multiple logistic regression showed that occupation before retirement,living pattern,the type of medical insurance,ADL,satisfaction of nursing service and length of residence were the major influencing factors (P<0.05).Conclusion The elderly in nursing homes have a high demand for caring behaviors.The nursing staff should consider the specific situation of them and do regular assessment,to provide safe,professional and holistic caring behaviors from different perspectives so as to improve their quality of life.

13.
J Ethnopharmacol ; 162: 253-60, 2015 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-25557032

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Gegenqinlian Decoction (GQD) has been used as a folk remedy for gastrointestinal diseases in China over thousands of years. It has significant treatment efficacy for patients with inflammatory bowel disease (IBD). We analyzed and showed that the active components alignment of Gegenqinlian Decoction (ACAG) possesses broad pharmacological effects including analgesic, antipyretic, anti-inflammatory, antibacterial, antiviral and antidiarrhea, as well as the effect of adjusting gastrointestinal function in our preliminary experiments. However, the exact molecular mechanisms on how ACAG exerts these pharmacological effects still remain elusive. In the present study, the plausible pharmacological effects of ACAG on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis were investigated. MATERIALS AND METHODS: Male Sprague-Dawley (SD) rats with TNBS/ethanol-induced colitis were used. The colonic wet weight, macroscopic and histological colon injury, superoxide dismutase (SOD), malonyldialdehyde (MDA), and inducible nitric oxide synthase (iNOS) activity were observed. Pro-inflammation cytokines were determined by ELISA methods, semi-quantitative RT-PCR and Immuno-histochemistry. RESULTS: We showed administration of ACAG was able to improve colitis. This was manifested by a decreased in the score of macroscopic and histological colonic injury, by lowered colonic wet weight, accompanied by significant increased of SOD activity, and decreased of MDA and iNOS activities. The treatment also significantly reduced tumor necrosis factor-alpha (TNF-α) and interleukin-1ß (IL-1ß) levels in colon and serum as well as the colonic mRNA levels for several inflammatory cytokines such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), macrophage inflammatory protein-2 (MIP-2), intercellular adhesion molecule-1 (ICAM-1) and toll-like receptor 2, 4 (TLR2, TLR4). In addition, we also showed that ACAG was able to inhibit the activation and translocation of transcription factors, nuclear factor kappaBp65 (NF-κBp65) in colon. CONCLUSIONS: Our results suggest that ACAG exhibits protective effect in TNBS-induced ulcerative colitis. We postulate that this might be due to its modulation of oxidant/anti-oxidant balance, downregulation of productions, expressions of pro-inflammatory cytokines and inhibition of NF-κBp65 signal transduction pathways.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Animais , Colite Ulcerativa/induzido quimicamente , Medicamentos de Ervas Chinesas/química , Masculino , Malondialdeído/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Organismos Livres de Patógenos Específicos , Superóxido Dismutase/metabolismo , Ácido Trinitrobenzenossulfônico/toxicidade
14.
Zhongguo Zhen Jiu ; 34(12): 1191-5, 2014 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-25876351

RESUMO

OBJECTIVE: With functional magnetic resonance imaging (fMRI), cerebral function imaging of acupuncture and sham acupuncture at Taichong (LR 3) in patients with essential hypertension (EH) was observed to analyze central mechanism of Taichong (LR 3) to treat EH. METHODS: Eighteen EH patients were divided into a twisting acupuncture group (10 cases) and a sham acupuncture group (8 cases), which were treated with twisting manipulation and sham acu- puncture at right Taichong (LR 3), respectively. The treatments were both given with 30-second manipulation and 30- second interval for totally 5 min. During the acupuncture, fMRI was adopted to scan the cerebral function imaging of EH patients on resting state, and the acquired data were analyzed with SPM2 module in Matlab software. RESULTS: Acupunc- ture at Taichong (LR 3) in EH patients mainly increased opposite-side oxygen consumption, which generally activated left anterior cingulated gyrus (BA 32), left inferior parietal lobule (BA 40), left inferior temporal gyrus (BA 19), left middle temporal gyrus (BA 37) and right anterior central gyrus (BA 6). The activated areas were related to motor, vision and cognition of emotion. Stimulation region of sham acupuncture mainly included right anterior cingulated gyrus (BA 24), left inferior parietal lobule (BA 40) and left inferior frontal gyrus (BA 7). CONCLUSION: The central mechanism of Tai- chong (LR 3) on antihypertensive effect and symptom improvement is not in thalamus and medulla that are traditionally believed to control blood pressure. Taichong (LR 3) could activate anterior cingulated gyrus to regulate parasympathetic nerve and lower blood pressure, and through anterior cingulated gyrus, the connection with the surrounding areas is strengthened to improve the cognitive impairment caused by long-term hypertension.


Assuntos
Terapia por Acupuntura , Hipertensão/terapia , Pontos de Acupuntura , Adulto , Idoso , Encéfalo/diagnóstico por imagem , Cognição , Hipertensão Essencial , Feminino , Humanos , Hipertensão/diagnóstico por imagem , Hipertensão/psicologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Radiografia
15.
Chinese Acupuncture & Moxibustion ; (12): 1191-1195, 2014.
Artigo em Chinês | WPRIM | ID: wpr-277270

RESUMO

<p><b>OBJECTIVE</b>With functional magnetic resonance imaging (fMRI), cerebral function imaging of acupuncture and sham acupuncture at Taichong (LR 3) in patients with essential hypertension (EH) was observed to analyze central mechanism of Taichong (LR 3) to treat EH.</p><p><b>METHODS</b>Eighteen EH patients were divided into a twisting acupuncture group (10 cases) and a sham acupuncture group (8 cases), which were treated with twisting manipulation and sham acu- puncture at right Taichong (LR 3), respectively. The treatments were both given with 30-second manipulation and 30- second interval for totally 5 min. During the acupuncture, fMRI was adopted to scan the cerebral function imaging of EH patients on resting state, and the acquired data were analyzed with SPM2 module in Matlab software.</p><p><b>RESULTS</b>Acupunc- ture at Taichong (LR 3) in EH patients mainly increased opposite-side oxygen consumption, which generally activated left anterior cingulated gyrus (BA 32), left inferior parietal lobule (BA 40), left inferior temporal gyrus (BA 19), left middle temporal gyrus (BA 37) and right anterior central gyrus (BA 6). The activated areas were related to motor, vision and cognition of emotion. Stimulation region of sham acupuncture mainly included right anterior cingulated gyrus (BA 24), left inferior parietal lobule (BA 40) and left inferior frontal gyrus (BA 7).</p><p><b>CONCLUSION</b>The central mechanism of Tai- chong (LR 3) on antihypertensive effect and symptom improvement is not in thalamus and medulla that are traditionally believed to control blood pressure. Taichong (LR 3) could activate anterior cingulated gyrus to regulate parasympathetic nerve and lower blood pressure, and through anterior cingulated gyrus, the connection with the surrounding areas is strengthened to improve the cognitive impairment caused by long-term hypertension.</p>


Assuntos
Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pontos de Acupuntura , Terapia por Acupuntura , Encéfalo , Diagnóstico por Imagem , Cognição , Hipertensão Essencial , Hipertensão , Diagnóstico por Imagem , Psicologia , Terapêutica , Imageamento por Ressonância Magnética , Radiografia
16.
PLoS One ; 8(12): e83060, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24340079

RESUMO

Trace elements have been recognized to play an important role in the development of Parkinson's disease (PD). However, it is difficult to precisely identify the relationship between these elements and the progression of PD because of an insufficient number of patients. In this study, quantifications of selenium (Se), copper (Cu), iron (Fe) and zinc (Zn) by atomic absorption spectrophotometry were performed in plasma from 238 PD patients and 302 controls recruited from eastern China, which is so far the largest cohort of PD patients and controls for measuring plasma levels of these elements. We found that plasma Se and Fe concentrations were significantly increased whereas Cu and Zn concentrations decreased in PD patients as compared with controls. Meanwhile, these four elements displayed differential changes with regard to age. Linear and logistic regression analyses revealed that both Fe and Zn were negatively correlated with age in PD patients. Association analysis suggests that lower plasma Se and Fe levels may reduce the risk for PD, whereas lower plasma Zn is probably a PD risk factor. Finally, a model was generated to predict PD patients based on the plasma concentrations of these four trace elements as well as other features such as sex and age, which achieved an accuracy of 80.97±1.34% using 10-fold cross-validation. In summary, our data provide new insights into the roles of Se, Cu, Fe and Zn in PD progression.


Assuntos
Cobre/sangue , Ferro/sangue , Doença de Parkinson/sangue , Selênio/sangue , Zinco/sangue , Fatores Etários , Idoso , Estudos de Casos e Controles , China , Estudos de Coortes , Progressão da Doença , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Reprodutibilidade dos Testes , Espectrofotometria Atômica
17.
Planta Med ; 78(14): 1574-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22814888

RESUMO

From the aerial part of Abies recurvata, 62 miscellaneous chemical constituents were isolated including 6 new and 56 known ones. The new compounds comprised three monoterpenes, two diterpenes, and one lignan. Their chemical structures were characterized on the basis of various spectroscopic techniques. Dihydrodehydrodiconiferyl alcohol (35) showed the strongest inhibitory effects against lipopolysaccharide-induced nitric oxide production in RAW 264.7 cells with an IC50 value of 66.4 µM.


Assuntos
Abies/química , Diterpenos/química , Lignanas/química , Monoterpenos/química , Extratos Vegetais/química , Triterpenos/química , Animais , Linhagem Celular Tumoral , Diterpenos/isolamento & purificação , Diterpenos/farmacologia , Concentração Inibidora 50 , Lignanas/isolamento & purificação , Lignanas/farmacologia , Lignina/análogos & derivados , Lignina/farmacologia , Lipopolissacarídeos/efeitos adversos , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Monoterpenos/isolamento & purificação , Monoterpenos/farmacologia , Óxido Nítrico/análise , Óxido Nítrico/metabolismo , Componentes Aéreos da Planta/química , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Triterpenos/isolamento & purificação , Triterpenos/farmacologia
18.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(2): 123-30, 2011 03.
Artigo em Chinês | MEDLINE | ID: mdl-21488206

RESUMO

OBJECTIVE: To construct HEK293 cell lines stably expressing hCysLT(2) receptor, and to evaluate its application in screening of synthetic compounds with antagonist activity. METHODS: The recombinant plasmid pcDNA3.1(+)-hCysLT(2) was transfected into HEK293 cells using Lipofectamin 2000. The transfected HEK293 cells were selected in 96 well plates by limiting dilution with 600 µg/ml C418 for 8 weeks. The expression of human CysLT(2) receptor was detected by RT-PCR and immunofluorescence staining. In HEK293 cells stably transfected with hCysLT(2), the agonist LTD(4)-induced elevation of intracellular calcium concentration ([Ca2(+)]i) was measured as the index for screening compounds with antagonist activity. RESULT: After selection in 96 well plates by limiting dilution, 12 monoclones were obtained and 11 of them highly expressed hCysLT(2) receptor. The positive control ATP at 50 µmol/L and LTD(4) at 100 nmol/L elevated [Ca2(+)]i in hCysLT(2)-HEK293 cells. AP-2100984 inhibited LTD(4)-induced [Ca2(+)]i elevation, but selective CysLT(1) receptor antagonists did not exert such an effect. The newly synthesized compounds DXW2, DXW3, DXW4, DXW5, DXW9, DXW25, DXW26, DXW29 and DXW35 at 1 µmol/L significantly inhibited LTD(4)-induced [Ca2(+)]i elevation. The IC(50) values of DXW4 and DXW5 were 0.25 µmol/L and 7.5 µmol/L. CONCLUSION: HEK293 cell lines stably expressing hCysLT(2) receptor have been successfully constructed, and can be used to screen compounds with CysLT(2) receptor antagonist activity.


Assuntos
Células HEK293 , Receptores de Leucotrienos/genética , Avaliação Pré-Clínica de Medicamentos , Humanos , Antagonistas de Leucotrienos , Transfecção
19.
Artigo em Chinês | WPRIM | ID: wpr-319821

RESUMO

<p><b>OBJECTIVE</b>To construct HEK293 cell lines stably expressing hCysLT(2) receptor, and to evaluate its application in screening of synthetic compounds with antagonist activity.</p><p><b>METHODS</b>The recombinant plasmid pcDNA3.1(+)-hCysLT(2) was transfected into HEK293 cells using Lipofectamin 2000. The transfected HEK293 cells were selected in 96 well plates by limiting dilution with 600 μg/ml C418 for 8 weeks. The expression of human CysLT(2) receptor was detected by RT-PCR and immunofluorescence staining. In HEK293 cells stably transfected with hCysLT(2), the agonist LTD(4)-induced elevation of intracellular calcium concentration ([Ca2(+)]i) was measured as the index for screening compounds with antagonist activity.</p><p><b>RESULT</b>After selection in 96 well plates by limiting dilution, 12 monoclones were obtained and 11 of them highly expressed hCysLT(2) receptor. The positive control ATP at 50 μmol/L and LTD(4) at 100 nmol/L elevated [Ca2(+)]i in hCysLT(2)-HEK293 cells. AP-2100984 inhibited LTD(4)-induced [Ca2(+)]i elevation, but selective CysLT(1) receptor antagonists did not exert such an effect. The newly synthesized compounds DXW2, DXW3, DXW4, DXW5, DXW9, DXW25, DXW26, DXW29 and DXW35 at 1 μmol/L significantly inhibited LTD(4)-induced [Ca2(+)]i elevation. The IC(50) values of DXW4 and DXW5 were 0.25 μmol/L and 7.5 μmol/L.</p><p><b>CONCLUSION</b>HEK293 cell lines stably expressing hCysLT(2) receptor have been successfully constructed, and can be used to screen compounds with CysLT(2) receptor antagonist activity.</p>


Assuntos
Humanos , Avaliação Pré-Clínica de Medicamentos , Células HEK293 , Antagonistas de Leucotrienos , Receptores de Leucotrienos , Genética , Transfecção
20.
Zhonghua Yu Fang Yi Xue Za Zhi ; 44(8): 726-30, 2010 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21055024

RESUMO

OBJECTIVE: To explore the effects of thyroid hormone on the expression of homeobox gene Nkx2.1 mRNA in child rat by supplying their hypothyroidism pregnant mother with different dose of levothyroxine (L-thyroxine, L-T(4)) in different times. METHODS: 120 female Wistar rats were randomly divided into eight groups according to the body weight: control group, non-treatment hypothyroidism group, hypothyroidism groups supplied with L-T(4) in high, medium and low dosage in early stage (1st-17th day of pregnancy) and in late stage (18th day of pregnancy-20th day after childbirth). According to 100 grams of body weight, the concentrations of L-T(4) were 3.5, 2.0, 0.5 µg/d in high, medium and low dosage group. All the rats were fed with low-iodine food. The control group was given 200 µg/L potassium iodate solution as drinking water and the other groups were given deionized water. After three months, the rats were mated with normal male rats. After the pregnancy was confirmed, hypothyroidism groups were supplied with L-T(4) of different concentrations. Brain samples were taken from the 17-day fetal rats, new-born and 20-day old offsprings and the levels of Nkx2.1 mRNA in brain tissue were analyzed by real-time fluorescence quantitative PCR techniques. RESULTS: The levels of TT(3) in hypothyroidism groups supplied with L-T(4) in high, medium and low dosages in early and late pregnant stages, non-treatment hypothyroidism group and control group were (0.85 ± 0.17), (0.81 ± 0.18), (0.86 ± 0.21), (0.85 ± 0.20), (0.89 ± 0.18), (0.85 ± 0.20), (0.86 ± 0.20), (1.08 ± 0.07) nmol/L (F = 4.08, P < 0.01); the levels of TT(4) in each group were (0.43 ± 0.16), (0.39 ± 0.11), (0.39 ± 0.13), (0.43 ± 0.17), (0.51 ± 0.19), (0.43 ± 0.16), (0.41 ± 0.15), (39.43 ± 14.16) nmol/L (F = 31.99, P < 0.01); the levels of FT(3) in each group were (3.29 ± 0.61), (3.29 ± 0.61), (3.24 ± 0.61), (3.28 ± 0.63), (3.31 ± 0.59), (3.28 ± 0.50), (3.24 ± 0.49), (4.93 ± 0.46) pmol/L (F = 5.79, P < 0.01); the levels of FT(4) in each group were (3.38 ± 0.80), (3.31 ± 0.67), (3.29 ± 0.73), (3.27 ± 0.71), (3.48 ± 0.81), (3.56 ± 0.66), (3.29 ± 0.61), (27.29 ± 4.53) pmol/L (F = 26.34, P < 0.01). The expression of Nkx2.1 mRNA in non-treatment hypothyroidism group (9.15 × 10(-5) ± 9.17 × 10(-5)) was lower than control group (65.1 × 10(-5) ± 40.90 × 10(-5)) in 17th day of pregnancy (t = 66.224, P < 0.05); the expression of Nkx2.1 mRNA in non-treatment hypothyroidism group (3.16 × 10(-5) ± 0.142 × 10(-5)) was lower than control group (55.6 × 10(-5) ± 51.05 × 10(-5)) in new-born (t = 102.225, P < 0.05); the expression of Nkx2.1 mRNA in non-treatment hypothyroidism group (8.09 × 10(-5) ± 8.21 × 10(-5)) was lower than control group (13.9 × 10(-5) ± 7.43 × 10(-5)) in 20th day after birth (t = 9.235, P < 0.05). The trend of Nkx2.1 mRNA in hypothyroidism groups was decreased in group supplied with L-T(4) in medium dosage in early stage descends in 17th day of pregnancy, new-born and 20th day after birth (57.1 × 10(-5) ± 22.90 × 10(-5)), (30.8 × 10(-5) ± 27.20 × 10(-5)), (17.1 × 10(-5) ± 0.623 × 10(-5)) (F = 13.394, P < 0.01). The expression of Nkx2.1 mRNA in hypothyroidism groups supplied with L-T(4) in medium dosage in early stage in 17th day of pregnancy, new-born and 20th day after childbirth was closest to the control group in every period (t values were 0.225, 0.336, 0.345, all P values > 0.05). CONCLUSION: The difference in the expression of homeobox gene Nkx2.1 mRNA is highly related to the level of thyroid hormone.


Assuntos
Encéfalo/metabolismo , Hipotireoidismo/tratamento farmacológico , Proteínas Nucleares/genética , RNA Mensageiro/genética , Tiroxina/farmacologia , Fatores de Transcrição/genética , Animais , Animais Recém-Nascidos/genética , Animais Recém-Nascidos/metabolismo , Feminino , Gravidez , Prenhez , Ratos , Ratos Wistar , Fator Nuclear 1 de Tireoide
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