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OBJECTIVES: IL-1beta is a potent proinflammatory, pro-fibrogenetic and pro-athrosclerosis cytokine which has been shown to play an important role in an expanding number of noninfectious, chronic inflammatory conditions including cardiovascular disease, renal fibrosis, rheumatoid arthritis and even type 2 diabetes. Losartan is an angiotensin II receptor antagonist widely used for the treatment of hypertension, diabetic nephropathy and congestive heart failure. In this study, we attempted to clarify whether losartan has an inhibitory effect on IL-1beta. To further elucidate the molecular mechanism underlying the anti-IL-1beta property of losartan, we studied the LPS+ATP-induced activation of NALP3 inflammasome which controls the muturation and secretion of IL-1beta. METHODS: LPS and ATP were used to stimulate the release of IL-1beta from thioglycollate-elicited macrophages from BALB/c mice. The production of IL-1beta was evaluated by ELISA assay and NALP3, caspase-1, IL-beta mRNA levels were determined by reverse transcription-polymerase chain reaction. RESULTS: In cultured thioglycollate-elicited macrophages, we observed that LPS + ATP greatly enhanced IL-1 beta secretion (6938.00 +/- 83.45; P < 0.05) and the mRNA levels of NALP3, caspase-1 which are two main components of NALP3 inflammasome (60.88 +/- 8.28; 1.31 +/- 0.04, P < 0.05 for both). The macrophages co-cultured with losartan showed low production of IL-1beta (3907.50 +/- 143.61; P < 0.05) and low production of NALP3, caspase-1mRNA (29.82 +/- 6.92; 1.12 +/- 0.05, P < 0.05 for both). Losartan did not reduce IL-1beta mRNA(P > 0.05). CONCLUSIONS: Our results show that the NALP3 inflammasome is up-regulated and activated in the mouse macrophage in response to LPS + ATP stimulation. Losartan is able to suppress the LPS + ATP-induced production of IL-1beta protein. In addition, this effectmay be partially mediated by suppressing NALP3 inflammasome activation.
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Adenosina Trifosfato/antagonistas & inhibidores , Adenosina Trifosfato/farmacología , Bloqueadores del Receptor Tipo 1 de Angiotensina II/farmacología , Proteínas Portadoras/antagonistas & inhibidores , Proteínas Portadoras/inmunología , Interleucina-1beta/metabolismo , Lipopolisacáridos/antagonistas & inhibidores , Lipopolisacáridos/farmacología , Losartán/farmacología , Macrófagos/metabolismo , Animales , Proteínas Portadoras/biosíntesis , Caspasa 1/biosíntesis , ADN Complementario/biosíntesis , ADN Complementario/genética , Ensayo de Inmunoadsorción Enzimática , Inmunidad Celular/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , Proteína con Dominio Pirina 3 de la Familia NLR , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la PolimerasaRESUMEN
OBJECTIVE: To analyze the mechanism for the therapeutic effects of tumor necrosis factor α (TNFα) inhibition in a murine model of systemic lupus erythematosus. METHODS: We used the (NZB × NZW)F(1) (NZB/NZW) mouse model of interferon-α-induced lupus nephritis and treated mice with TNF receptor type II (TNFRII) Ig after TNFα expression was detected in the kidneys. Autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA), and autoantibody- forming cells were determined using an enzyme-linked immunospot assay. Activation of splenocytes was analyzed by flow cytometry. Kidneys were harvested and analyzed using flow cytometry, immunohistochemistry, ELISA, Western blotting, and real-time polymerase chain reaction. RESULTS: TNFRII Ig treatment stabilized nephritis and markedly prolonged survival. Autoantibody production and systemic immune activation were not inhibited, but the renal response to glomerular immune complex deposition was attenuated. This was associated with decreases in renal production of chemokines, renal endothelial cell activation, interstitial F4/80(high) macrophage accumulation, tubular damage, and oxidative stress. In contrast, perivascular lymphoid aggregates containing B cells, T cells, and dendritic cells accumulated unabated. CONCLUSION: Our data suggest that TNFα is a critical cytokine that amplifies the response of the nephron to immune complex deposition, but that it has less influence on the response of the systemic vasculature to inflammation.
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Complejo Antígeno-Anticuerpo/efectos de los fármacos , Riñón/efectos de los fármacos , Nefritis Lúpica/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Factor de Necrosis Tumoral alfa/inmunología , Animales , Complejo Antígeno-Anticuerpo/inmunología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Modelos Animales de Enfermedad , Interferón-alfa , Riñón/inmunología , Riñón/metabolismo , Glomérulos Renales/efectos de los fármacos , Glomérulos Renales/inmunología , Glomérulos Renales/metabolismo , Nefritis Lúpica/inducido químicamente , Nefritis Lúpica/inmunología , Nefritis Lúpica/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Bazo/efectos de los fármacos , Bazo/inmunología , Bazo/metabolismoRESUMEN
OBJECTIVE: Presenting treatment outcomes positively or negatively may differently influence treatment preferences and lead to sub-optimal decision in a medical context. This review systematically organised how positive versus negative framing of treatment outcomes influenced cancer treatment decisions of cancer patients and individuals without a cancer diagnosis. DESIGN: Three databases (PubMed, PsycInfo and Scopus) were searched for studies reporting the effects of positive versus negative framing on cancer treatment decision-making from 1981 to December 2020. MAIN OUTCOME MEASURE: The effects of positive versus negative framing on cancer treatment preferences and the elimination of framing effect were evaluated. RESULTS: A total of 12 studies that met inclusion criteria were reviewed. Framing effect was consistently observed in individuals without a cancer diagnosis. There was not enough evidence to suggest a robust framing effect in cancer patients. Surgery was preferred in positive framing, whereas adjuvant therapy was preferred in negative framing. Justification intervention significantly eliminated framing effect. Mixed framing failed to eliminate framing effect. CONCLUSION: Current recommendations for presenting treatment options are based on research in cancer-screening decision-making. Knowledge of how positive versus negative framing affect cancer patients' treatment decisions is still limited. Our review highlighted the need for continued research in this area.
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OBJECTIVES: Adolescents may suffer from binge eating (BE), that refers to consuming a large amount of food in a short period of time and accompanied by feelings of loss of control (LOC) over eating. This study compared the prevalence of BE between 16-year-old Malaysian girls from two types of public schools, Malay-English-medium and Chinese-Malay-English-medium schools. Additionally, this study identified associated risk factors of those who presented regular BE episodes, including LOC eating, anxiety, body mass index (BMI), body dissatisfaction (BD) and eating disorders (EDs) psychopathology. METHODS: 398 participants completed self-reports assessing BE symptoms, LOC eating, state anxiety, trait anxiety, EDs psychopathology, and BD. They also reported heights and weights. Descriptive statistics, t-tests, chi-square tests, and Z-test for independent proportions were conducted. RESULTS: There was no significant difference in either the prevalence of BE or EDs psychopathology between participants from the two types of schools. 71 (17.8â¯%) participants reported moderate-to-severe symptoms of BE, and 46 (11.6â¯%) reported moderate-to-severe levels of LOC eating. Those who reported moderate-to-severe symptoms of BE reported significantly higher levels of LOC eating, BD, drive to be thinner, BMI, state anxiety, and EDs psychopathology, compared to those who reported none-to-minimal BE. CONCLUSIONS: BE and LOC eating appeared to be relatively common among secondary school girls in Malaysia. The relatively high prevalence of BE amongst adolescents in our sample highlighted the importance of early identification of signs for BE as preventive measures from developing EDs psychopathology among children and adolescents. We propose that attitudes towards eating and body image-related concerns should be included in school screenings aimed at preventing psychological problems in minors.
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Trastorno por Atracón , Trastornos de Alimentación y de la Ingestión de Alimentos , Adolescente , Niño , Femenino , Humanos , Trastorno por Atracón/epidemiología , Trastorno por Atracón/psicología , Trastornos de Alimentación y de la Ingestión de Alimentos/epidemiología , Conducta Alimentaria/psicología , Índice de Masa Corporal , Ansiedad/epidemiología , Ansiedad/psicologíaRESUMEN
Fluorofenidone (FD) is a novel pyridone agent with significant antifibrotic effects in vitro. The purpose of this study is to investigate the effects of FD on renal interstitial fibrosis in rats with obstructive nephropathy caused by unilateral ureteral obstruction (UUO). With pirfenidone (PD, 500 mg/kg/day) and enalapril (10 mg/kg/day) as the positive treatment controls, the rats in different experimental groups were administered with FD (500 mg/kg/day) from day 4 to day 14 after UUO. The tubulointerstitial injury, interstitial collagen deposition, and expression of type I and type III collagen, transforming growth factor-ß(1) (TGF-ß(1)), connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), α-smooth muscle actin (α-SMA), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed. FD treatment significantly attenuated the prominently increased scores of tubulointerstitial injury, interstitial collagen deposition, and protein expression of type I and type III collagen in ureter-obstructed kidneys, respectively. As compared with untreated rats, FD also significantly reduced the expression of α-SMA, TGF-ß(1), CTGF, PDGF, and inhibitor of TIMP-1 in the obstructed kidneys. Fluorofenidone attenuates renal interstitial fibrosis in the rat model of obstructive nephropathy through its regulation on fibrogenic growth factors, tubular cell transdifferentiation, and extracellular matrix.
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Enfermedades Renales/tratamiento farmacológico , Túbulos Renales/patología , Piridonas/farmacología , Obstrucción Ureteral/complicaciones , Actinas/metabolismo , Animales , Colágeno Tipo I/metabolismo , Colágeno Tipo III/metabolismo , Factor de Crecimiento del Tejido Conjuntivo/genética , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Evaluación Preclínica de Medicamentos , Fibrosis , Enfermedades Renales/etiología , Enfermedades Renales/patología , Túbulos Renales/metabolismo , Masculino , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Factor de Crecimiento Derivado de Plaquetas/genética , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Piridonas/uso terapéutico , Ratas , Ratas Sprague-Dawley , Inhibidor Tisular de Metaloproteinasa-1/genética , Inhibidor Tisular de Metaloproteinasa-1/metabolismo , Transcripción Genética , Factor de Crecimiento Transformador beta1/genética , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
Bone marrow mesenchymal stem cells (BMSCs) have multi-lineage differentiation potential and play an important role in tissue repair. Studies have shown that BMSCs gather at the injured tissue site after granulocyte-colony stimulating factor (G-CSF) administration. In this study, we first investigated whether G-CSF could promote BMSC homing to damaged lung tissue induced by bleomycin (BLM) and then investigated whether SDF-1/CXCR4 chemotaxis might be involved in this process. Next, we further studied the potential inhibitory effect of G-CSF administration in mice with lung fibrosis induced by bleomycin. We examined both the antifibrotic effects of G-CSF in mice with bleomycin-induced pulmonary fibrosis in vivo and its effects on the proliferation, differentiation and chemotactic movement of cells in vitro. Flow cytometry, real-time PCR, transwell and Cell Counting Kit-8 (CCK-8) assays were used in this study. The results showed that both preventative and therapeutic G-CSF administration could significantly inhibit bleomycin-induced pulmonary fibrosis. G-CSF enhanced BMSC migration to lung tissues, but this effect could be alleviated by AMD3100, which blocked the SDF-1/CXCR4 axis. We also found that BMSCs could inhibit fibroblast proliferation and transdifferentiation into myofibroblasts through paracrine actions. In conclusion, G-CSF exerted antifibrotic effects in bleomycin-induced lung fibrosis, in part by promoting BMSC homing to injured lung tissues via SDF-1/CXCR4 chemotaxis.
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Quimiocina CXCL12/metabolismo , Quimiotaxis/efectos de los fármacos , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Células Madre Mesenquimatosas/efectos de los fármacos , Fibrosis Pulmonar/tratamiento farmacológico , Receptores CXCR4/metabolismo , Animales , Bleomicina , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Factor Estimulante de Colonias de Granulocitos/farmacología , Ratones , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
AIM: Fluorofenidone (1-(3-fluorophenyl)-5-methyl-2-(1H)-pyridone) is a novel pyridone agent. The aim of the present study is to investigate the effects of fluorofenidone on angiotensin (Ang)II-induced fibrosis and the involved molecular mechanism in rat proximal tubular epithelial cells. METHODS: NRK-52E cells, a rat proximal tubular epithelial cell line, were incubated with medium containing AngII, with or without nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitor diphenylene iodonium (DPI), losartan, fluorofenidone (2, 4 and 8 mmol/L) and pirfenidone (8 mmol/L) for 24 h. Cells in the serum-free medium were controls. The expression of three subunits of NADPH oxidase, including p47phox, Nox-4 and p22phox, were determined by real-time reverse transcription polymerase chain reaction (RT-PCR) and western blot. NADPH oxidase activity was measured directly by superoxide dismutase (SOD) inhibitable cytochrome C reduction assay. The generation of reactive oxygen species (ROS) was measured by dichlorofluorescein fluorescence analysis. The mRNA and protein expression of collagen I and transforming growth factor (TGF)-beta1 were determined by real-time RT-PCR and enzyme-linked immunosorbent assay. RESULTS: Fluorofenidone significantly inhibited TGF-beta1 and collagen I expression upregulation induced by AngII or TGF-beta1 respectively. Moreover, fluorofenidone greatly reduced the elevation of expression and activity of NADPH oxidase and inhibited ROS generation induced by AngII in rat proximal tubular epithelial cells. These responses were also attenuated by DPI, losartan, and pirfenidone. CONCLUSION: Fluorofenidone acted as an anti-oxidative and anti-fibrotic agent through the mechanisms of blocking NADPH oxidase-dependent oxidative stress and inhibiting TGF-beta1 expression in rat proximal tubular epithelial cells.
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Colágeno Tipo I/antagonistas & inhibidores , Fibrosis/tratamiento farmacológico , NADPH Oxidasas/fisiología , Piridonas/farmacología , Factor de Crecimiento Transformador beta1/antagonistas & inhibidores , Animales , Células Cultivadas , Colágeno Tipo I/genética , Riñón/patología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , NADPH Oxidasas/genética , Ratas , Superóxidos/metabolismo , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
OBJECTIVES: This study was aimed to compare the effectiveness of aromatherapy and acupressure massage intervention strategies on the sleep quality and quality of life (QOL) in career women. DESIGN: The randomized controlled trial experimental design was used in the present study. One hundred and thirty-two career women (24-55 years) voluntarily participated in this study and they were randomly assigned to (1) placebo (distilled water), (2) lavender essential oil (Lavandula angustifolia), (3) blended essential oil (1:1:1 ratio of L. angustifolia, Salvia sclarea, and Origanum majorana), and (4) acupressure massage groups for a 4-week treatment. The Pittsburgh Sleep Quality Index and Short Form 36 Health Survey were used to evaluate the intervention effects at pre- and postintervention. RESULTS: After a 4-week treatment, all experimental groups (blended essential oil, lavender essential oil, and acupressure massage) showed significant improvements in sleep quality and QOL (p < 0.05). Significantly greater improvement in QOL was observed in the participants with blended essential oil treatment compared with those with lavender essential oil (p < 0.05), and a significantly greater improvement in sleep quality was observed in the acupressure massage and blended essential oil groups compared with the lavender essential oil group (p < 0.05). CONCLUSIONS: The blended essential oil exhibited greater dual benefits on improving both QOL and sleep quality compared with the interventions of lavender essential oil and acupressure massage in career women. These results suggest that aromatherapy and acupressure massage improve the sleep and QOL and may serve as the optimal means for career women to improve their sleep and QOL.
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Acupresión , Aromaterapia , Trastornos del Sueño-Vigilia/terapia , Mujeres Trabajadoras , Adulto , Femenino , Humanos , Persona de Mediana Edad , Calidad de Vida , Sueño/fisiología , Encuestas y Cuestionarios , Mujeres Trabajadoras/psicología , Mujeres Trabajadoras/estadística & datos numéricosAsunto(s)
Antivirales/uso terapéutico , Virus de la Hepatitis B/fisiología , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Carga Viral , Antivirales/farmacología , ADN Viral/sangre , Hepatitis B/sangre , Antígenos de Superficie de la Hepatitis B/sangre , Antígenos e de la Hepatitis B/sangre , Virus de la Hepatitis B/efectos de los fármacos , Humanos , Interferón-alfa/farmacología , Interferón-alfa/uso terapéutico , Cinética , Lamivudine/farmacología , Lamivudine/uso terapéutico , Modelos EstadísticosRESUMEN
PURPOSE: This study investigated the impact of arms/hands and body position on the measurement of breast density using MRI. METHODS: Noncontrast-enhanced T1-weighted images were acquired from 32 healthy women. Each subject received four MR scans using different experimental settings, including a high resolution hands-up, a low resolution hands-up, a high resolution hands-down, and finally, another high resolution hands-up after repositioning. The breast segmentation was performed using a fully automatic chest template-based method. The breast volume (BV), fibroglandular tissue volume (FV), and percent density (PD) measured from the four MR scan settings were analyzed. RESULTS: A high correlation of BV, FV, and PD between any pair of the four MR scans was noted (r > 0.98 for all). Using the generalized estimating equation method, a statistically significant difference in mean BV among four settings was noted (left breast, score test p = 0.0056; right breast, score test p = 0.0016), adjusted for age and body mass index. Despite differences in BV, there were no statistically significant differences in the mean PDs among the four settings (p > 0.10 for left and right breasts). Using Bland-Altman plots, the smallest mean difference/bias and standard deviations for BV, FV, and PD were noted when comparing hands-up high vs low resolution when the breast positions were exactly the same. CONCLUSIONS: The authors' study showed that BV, FV, and PD measurements from MRI of different positions were highly correlated. BV may vary with positions but the measured PD did not differ significantly between positions. The study suggested that the percent density analyzed from MRI studies acquired using different arms/hands and body positions from multiple centers can be combined for analysis.
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Mama/fisiología , Imagen por Resonancia Magnética/métodos , Postura , Adulto , Envejecimiento/patología , Envejecimiento/fisiología , Brazo/anatomía & histología , Brazo/fisiología , Pueblo Asiatico , Índice de Masa Corporal , Mama/anatomía & histología , Estudios de Cohortes , Femenino , Mano/anatomía & histología , Mano/fisiología , Humanos , Procesamiento de Imagen Asistido por Computador , Persona de Mediana Edad , Postura/fisiología , Adulto JovenRESUMEN
Our understanding of the mechanisms underlying the development of pancreatic cancer has been greatly advanced. However, the molecular events involved in the initiation and development of pancreatic cancer remain inscrutable. None of the present medical technologies have been proven to be effective in significantly improving early detection or reducing the mortality/morbidity of this disease. Thus, a better understanding of the molecular basis of pancreatic cancer is required for the identification of more effective diagnostic markers and therapeutic targets. Non-coding RNAs (ncRNAs), generally including microRNAs and long non-coding RNAs, have recently been found to be deregulated in many human cancers, which provides new opportunities for identifying both functional drivers and specific biomarkers of pancreatic cancer. In this article, we review the existing literature in the field documenting the significance of aberrantly expressed and functional ncRNAs in human pancreatic cancer, and discuss how oncogenic ncRNAs may be involved in the genetic and epigenetic networks regulating functional pathways that are deregulated in this malignancy, particularly of the ncRNAs' role in drug resistance and epithelial-mesenchymal transition biological phenotype, with the aim of analyzing the feasibility of clinical application of ncRNAs in the diagnosis and treatment of pancreatic cancer.
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Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Neoplasias Pancreáticas/genética , ARN no Traducido/genética , Microambiente Tumoral , Animales , Biomarcadores de Tumor/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/terapia , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Pruebas Genéticas , Terapia Genética , Humanos , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/terapia , Valor Predictivo de las Pruebas , Pronóstico , ARN no Traducido/metabolismoRESUMEN
The effect of chronic immobilization stress (CIS) on the biochemical parameters has been one of the hot topics in neuroscience. The aim of this study was to investigate the effects of CIS on the levels of glucocorticoid receptor (GR), corticotrophin-releasing factor (CRF) mRNA and proopiomelanocortin (POMC) mRNA in brains of rats. The rats were randomly divided into stressed and control groups. The stressed group was given CIS 3 h a day for 21 days continuously. GR of rats' hippocampus and prefrontal cortex (PFC) were detected by immunohistochemistry method. In addition, the CRF mRNA and POMC mRNA of rats' brain regions (hypothalamus, pituitary, hippocampus, and PFC) were detected by reverse transcription-polymerase chain reaction (RT-PCR). After exposure to CIS for 21 days, the GR immuno staining (the gray values) of the stressed group was less than that of the control group in hippocampal CA(1), dentate gyrus, and PFC (P < 0.01). Quantitative analysis indicated the presence of CRF mRNA in hypothalamus and pituitary, while POMC mRNA in PFC, hippocampus and pituitary of the stressed group was less than that of the control group (P < 0.01). The decreased levels of GR, CRF mRNA, and POMC mRNA in different brain regions may contribute to explanation of the CIS induced mechanism.
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Encéfalo/fisiología , Hormona Liberadora de Corticotropina/genética , Proopiomelanocortina/genética , Receptores de Glucocorticoides/metabolismo , Estrés Fisiológico/metabolismo , Estrés Fisiológico/fisiopatología , Animales , Enfermedad Crónica , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Restricción Física , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
AIM: To observe the effect of Xiaoyao Powder on the content changes of CRF mRNA in relative brain zone (hypothalamus, pituitary, hippocampus, cortex) in chronic restrained stress rats. METHODS: RT-PCR and graphic analysis methods were applied to test the content changes of CRF mRNA in relative brain zone. RESULTS: The CRF-1 gene expression in hypothalamus was modulated lower in stress group and the difference was significant when compared with control group (P < 0.01). The gene expression of CRF-1 in Xiaoyao Powder group was markedly modulated lower in hypothalamus, but it was markedly modulated higher in cortex as compared with control group (P < 0.01). The gene expression of CRF-2 in Xiaoyao Powder group was higher in hypothalamus than that in stress group (P < 0.01), and it was also higher in hippocampus as compared with that in control and stress group (P < 0.01, P < 0.05 respectively). CONCLUSION: The modulation point of Xiaoyao Powder group on central neuropeptide of chronic restrained stress is respectively hypothalamus, pituitary, hippocampus and cortex. The modulating target is hypothalamus, the limbic system and the cortex center. It can be suggested that medicine of smoothing the liver simultaneously have poly-target and dual-modulating action and been involved in the integration function of nerve-endocrine-immune net.