Apigenin ameliorates non-eosinophilic inflammation, dysregulated immune homeostasis and mitochondria-mediated airway epithelial cell apoptosis in chronic obese asthma via the ROS-ASK1-MAPK pathway.

BACKGROUND: Obese asthma is one of the important asthma phenotypes that have received wide attention in recent years. Excessive oxidative stress and different inflammatory endotypes may be important reasons for the complex symptoms, frequent aggravation, and resistance to traditional treatments of obese asthma. Apigenin (API), is a flavonoid natural small molecule compound with good anti-inflammatory and antioxidant activity in various diseases and proved to have the potential efficacy to combat obese asthma. METHODS: In vivo, this study fed C57BL/6 J mice with high-fat diets(HFD)for 12 weeks and then stimulated them with OVA for 6 weeks to establish a model of chronic obese asthma, while different doses of oral API or dexamethasone were used for therapeutic interventions. In vitro, this study used HDM to stimulate human bronchial cells (HBEs) to establish the model and intervened with API or Selonsertib (SEL). RESULTS: This study clarified that OVAinduced a type of mixed granulocytic asthma with elevated neutrophils and eosinophils in obese male mice fed with long-term HFD, which also exhibited mixed TH17/TH1/TH2 inflammation. Apigenin effectively suppressed this complex inflammation and acted as a regulator of immune homeostasis. Meanwhile, apigenin reduced AHR, inflammatory cell infiltration, airway epithelial cell apoptosis, airway collagen deposition, and lung oxidative stress via the ROS-ASK1-MAPK pathway in an obese asthma mouse model. In vitro, this study found that apigenin altered the binding status of TRAF6 to ASK1, inhibited ASK1 phosphorylation, and protected against ubiquitin-dependent degradation of ASK1, suggesting that ROS-activated ASK1 may be an important target for apigenin to exert anti-inflammatory and anti-apoptotic effects. To further verify the intervention mechanism, this study clarified that apigenin improved cell viability and mitochondrial function and inhibited apoptosis by interfering with the ROS-ASK1-MAPK pathway. CONCLUSIONS: This study demonstrates for the first time the therapeutic effect of apigenin in chronic obese asthma and further clarifies its potential therapeutic targets. In addition, this study clarifies the specificity of chronic obese asthma and provides new options for its treatment.

Louki Zupa decoction attenuates the airway inflammation in acute asthma mice induced by ovalbumin through IL-33/ST2-NF-κB/GSK3ß/mTOR signalling pathway.

CONTEXT: Asthma is a common respiratory system disease. Louki Zupa decoction (LKZP), a traditional Chinese medicine, presents a promising efficacy against lung diseases. OBJECTIVE: To investigate the pathogenic mechanism of asthma and reveal the intervention mechanism of LKZP. MATERIALS AND METHODS: Forty-eight female Balb/c mice were randomly divided into 6 groups: normal control group (NC), ovalbumin (OVA)/saline asthma model group, OVA/LL group, OVA/LM group, OVA/LH group and OVA/DEX group (n = 8 per group). The asthmatic mice were modelled through intraperitoneal injecting and neutralizing OVA. LKZP decoction was administrated by gavage at the challenge stage for seven consecutive days (2.1, 4.2 and 8.4 g/kg/day). We investigated the change in lung function, airway inflammation, mucus secretion and TH-1/TH-2-related cytokines. We further verify the activated status of the IL-33/ST2/NF-κB/GSK3ß/mTOR signalling pathway. RESULTS: LKZP was proved to improve asthmatic symptoms, as evidenced by the down-regulated airway resistance by 36%, 58% and 53% (p < 0.01, p < 0.001 vs. OVA/saline group), up-regulated lung compliance by 102%, 114% and 111%, decreased airway inflammation and mucus secretion by 33%, 40% and 33% (p < 0.001 vs. OVA/saline group). Moreover, the content of cytokines in BALF related to airway allergy (such as IgE) and T helper 1/T helper 2 cells (like IL-2, IL-4, IL-5, IL-13, TNF-α and IFN-γ), were also markedly reduced by 13-65% on LKZP intervention groups compared with model group. Mechanistic research revealed that the IL-33/ST2-NF-κB/GSK3ß/mTOR signalling pathway was activated in the OVA/saline group and LKZP significantly down-regulated this pathway. DISCUSSION AND CONCLUSION: LKZP improves lung function, airway inflammation, mucus secretion and correct immune imbalance by intervening with the IL-33/ST2-NF-κB/GSK3ß/mTOR signalling pathway, presenting a promising therapeutic choice for asthma.

Iristectorigenin A exerts novel protective properties against airway inflammation and mucus hypersecretion in OVA-induced asthmatic mice: Iristectorigenin A ameliorates asthma phenotype.

BACKGROUND: Despite the substantial amount of efforts made to reduce morbidity and improve respiratory management, asthma control remained a major challenge for severe patients. Plant isoflavones, one of the most estrogenic compounds, are considered a potential alternative therapy for asthma. Iristectorigenin A, a naturally occurring isoflavone, is extracted from a variety of medical plants and its biological activity has not been reported previously. PURPOSE: In present study, we aim to reveal the potential therapeutic role of Iristectorigenin A against acute asthmatic mice. STUDY DESIGN: We established ovalbumin (OVA) induced asthmatic murine model and orally administrated Iristectorigenin A at concentration of 5 and 10 mg/kg and dexamethasone as a positive control substance. METHODS: Asthmatic murine model was established with OVA sensitization and challenge. Lung function was assessed with FinePoint Ventilation system recording lung resistance (RI) and lung compliance (Cydn). White cells were sorted and counted in BALF. Histopathological assessment was conducted by H&E, PAS, and Masson's trichrome staining on paraffin embedded lung tissues. BALF content of IL-4, IL-5, IL-33, IL-13, INF-γ, IL-9 and serum IgE, IgG1 were measured using ELISA kit. Expression levels of mRNAs associated with inflammatory cytokines and goblet cell metaplasia were evaluated via quantitative RT-PCR. Protein expression levels of FOXA3, MUC5AC, SPDEF were estimated by immunohistochemistry on lung tissue, while NOTCH1 and NOTCH2 expressions were evaluated by western blotting analysis. RESULTS: Iristectorigenin A resulted in improved airway hyperresponsiveness (AHR) mirrored by decreased RI and increased Cydn. With Iristectorigenin A, we also observed reduced number of BALF leukocytes, improved inflammatory cell infiltration in lung tissue, decreased content of BALF IL-4, IL-5, IL-33, but not IL-13, INF-γ, IL-9, and their mRNA levels, along with decreased levels of OVA-specific IgE, IgG1 in asthmatic mice. Additionally, Iristectorigenin A exhibited significant therapeutic potential on attenuating mucus production reflected by mitigated FOXA3 and MUC5AC immunostaining on the airway epithelium, as well as decreased mRNAs associated with goblet cell metaplasia. At last, a decrease in elevated expression level of NOTCH2, but not NOTCH1, in asthmatic mice lung tissue was observed by western blotting analysis. CONCLUSION: Our study provides strong evidence that Iristectorigenin A can be potential therapeutic agent ameliorating airway inflammation and mucus hypersecretion in allergic asthma. This is a first research reported the potential of Iristectorigenin A as an alternative therapeutic agent.

Quantitative proteomic profiling of targeted proteins associated with Loki Zupa Decoction Treatment in OVA-Induced asthmatic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Loki Zupa (LKZP) decoction is one of the herbal prescriptions in traditional Uyghur medicine, which is commonly used for treating airway abnormality. However, underlying pathological mechanism and pathways involved has not been well studied. OBJECTIVES: In this paper, we aim to further confirmed the anti-inflammatory and anti-fibrotic role of LKZP decoction in airway, and uncover the passible mechanism involved via comprehensive quantitative proteomic DIA-MS analysis. MATERIALS AND METHODS: Mice asthmatic model was established with sensitizing and challenging with OVA. Lung function, pathological status, and inflammatory cytokines were assessed. Total of nine lung tissues were analyzed using proteomic DIA-MS analysis and 18 lung tissues were subjected to PRM validation. RESULTS: Total of 704 differentially expressed proteins (DEPs) (363 up regulated, 341 down regulated) were quantified in comparison of asthmatic and healthy mice, while 152 DEPs (91 up regulated, 61 down regulated) were quantified in LKZP decoction treated compared to asthmatic mice. Total of 21 proteins were overlapped between three groups. ECM-receptor interaction was significantly enriched and commonly shared between downregulated DEPs in asthma and upregulated DEPs in LKZP decoction treated mice. Total of 20 proteins were subjected to parallel reaction monitoring (PRM) analysis and 16 of which were quantified. At last, two proteins, RMB 10 and COL6A6, were validated with significant difference (P < 0.001) in protein abundance. CONCLUSIONS: Our results suggest that attenuated airway inflammation and fibrosis caused by LKZP decoction may associated with ECM-receptor interaction and RMB 10 and COL6A6 may be targeted by LKZP decoction in OVA-induced asthmatic mice.

Benzoylaconine induces mitochondrial biogenesis in mice via activating AMPK signaling cascade.

The traditional Chinese medicine "Fuzi" (Aconiti Lateralis Radix Praeparata) and its three representative alkaloids, aconitine (AC), benzoylaconine (BAC), and aconine, have been shown to increase mitochondrial mass. Whether Fuzi has effect on mitochondrial biogenesis and the underlying mechanisms remain unclear. In the present study, we focused on the effect of BAC on mitochondrial biogenesis and the underlying mechanisms. We demonstrated that Fuzi extract and its three components AC, BAC, and aconine at a concentration of 50 µM significantly increased mitochondrial mass in HepG2 cells. BAC (25, 50, 75 µM) dose-dependently promoted mitochondrial mass, mtDNA copy number, cellular ATP production, and the expression of proteins related to the oxidative phosphorylation (OXPHOS) complexes in HepG2 cells. Moreover, BAC dose-dependently increased the expression of proteins involved in AMPK signaling cascade; blocking AMPK signaling abolished BAC-induced mitochondrial biogenesis. We further revealed that BAC treatment increased the cell viability but not the cell proliferation in HepG2 cells. These in vitro results were verified in mice treated with BAC (10 mg/kg per day, ip) for 7 days. We showed that BAC administration increased oxygen consumption rate in mice, but had no significant effect on intrascapular temperature. Meanwhile, BAC administration increased mtDNA copy number and OXPHOS-related protein expression and activated AMPK signaling in the heart, liver, and muscle. These results suggest that BAC induces mitochondrial biogenesis in mice through activating AMPK signaling cascade. BAC may have the potential to be developed as a novel remedy for some diseases associated with mitochondrial dysfunction.

Acupuncture Regulates the Balance of CD4+ T Cell Subtypes in Experimental Asthma Mice.

OBJECTIVE: To evaluate the involvement of different CD4+ T cell subtypes in the anti-asthmatic effects of acupuncture in asthmatic mice. METHODS: BALB/c mice were challenged by ovalbumin (OVA) for the establishment of experimental asthma model. Mice were divided into 4 groups by a random number table including the normal control, asthma model, acupuncture and sham acupuncture groups (14 per group). Acupoints Dazhui (GV 14), bilateral Fengmen (BL 12) and Feishu (BL 13) were selected for manual acupuncture treatment every other day for 4 weeks and Huantiao (GB 30) was selected for sham acupuncture. Airway hyperresponsiveness was examined by Buxco Pulmonary System. Pulmonary histopathology analysis was performed for inflammatory cell infiltration and mucus hypersecretion by haematoxylin eosin staining and periodic acid-Schiffstaining. Inflammatory mediators assays of serum were investigated by enzyme-linked immunosorbent assay and Bio-Plex. CD4+ T cell subpopulations including the expression levels of important factors in T lymphocyte polarization in lung tissue were examined by flow cytometric and Western blot analyses. Related pathways were detected by Western blot assay. RESULTS: Compared with the OVA-induced asthma model group, acupuncture could attenuate airway hyperresponsiveness, inhibit inflammatory cell infiltration and mucus hypersecretion (P<0.05 or P<0.01). Furthermore, acupuncture increased the expressions of T-bet and Foxp3+, the cell numbers of CD4+ interferon gamma (IFN-γ)+ and CD4+ Foxp3+ in lung tissue and the level of Treg type cytokine interleukin (IL)-10 in serum (P<0.05 or P<0.01). Meanwhile, acupuncture reduced the RAR-related orphan receptor gamma t (RORγt) level, the cell numbers of CD4+ IL-17A+ as well as the levels of IL-5, IL-13 and IL-17A in serum (P<0.05 or P<0.01). In addition, both acupuncture and sham acupuncture could inhibit the phosphorylation of p38 and p44/42 (P<0.01). CONCLUSION: Acupuncture could alleviate allergic airway inflammation by strengthening the activities of Th1 and Treg, thus regulating the balance of CD4+ T cell subtypes in experimental asthmatic mice.

Moxibustion upregulates hippocampal progranulin expression.

In China, moxibustion is reported to be useful and has few side effects for chronic fatigue syndrome, but its mechanisms are largely unknown. More recently, the focus has been on the wealth of information supporting stress as a factor in chronic fatigue syndrome, and largely concerns dysregulation in the stress-related hypothalamic-pituitary-adrenal axis. In the present study, we aimed to determine the effect of moxibustion on behavioral symptoms in chronic fatigue syndrome rats and examine possible mechanisms. Rats were subjected to a combination of chronic restraint stress and forced swimming to induce chronic fatigue syndrome. The acupoints Guanyuan (CV4) and Zusanli (ST36, bilateral) were simultaneously administered moxibustion. Untreated chronic fatigue syndrome rats and normal rats were used as controls. Results from the forced swimming test, open field test, tail suspension test, real-time PCR, enzyme-linked immunosorbent assay, and western blot assay showed that moxibustion treatment decreased mRNA expression of corticotropin-releasing hormone in the hypothalamus, and adrenocorticotropic hormone and corticosterone levels in plasma, and markedly increased progranulin mRNA and protein expression in the hippocampus. These findings suggest that moxibustion may relieve the behavioral symptoms of chronic fatigue syndrome, at least in part, by modulating the hypothalamic-pituitary-adrenal axis and upregulating hippocampal progranulin.

[Establishment of Social Stress Induced Depression-like Animal Model in Mice of C57BL/6 Strain and Behavioral Assessments].

OBJECTIVE: To establish social stress induced depression-like model in mice of C57BL/6 strain, and to assess its reliability using differenf behavioral methods. METHODS: Totally 20 male mice of C57BL/6 strain were divided into the normal group and the stress model group by random digit table,10 in each group. Another 10 CD1 mice were subjected to social stress. Mice in the normal control group received no stress, while those in the model group received social stress for 10 successive days. Behavioral assessment was performed using social interaction test (SIT), the elevated plus-maze (EPM) test, tail suspension test (TST), respectively. Serum cortisol level was detected by ELISA to assess the reliability of the model. RESULTS: In the social interaction test when the social target (CDI mice) was inexistent, mice in the normal control group spent longer time in the social interaction zone and less time in the corner zone (P < 0.05); mice in the model group spent less time in the social interaction zone and more time in the corner zone (P < 0.05). Compared with the normal group when CDI mice existed, mice in the model group spent less time in the social interaction zone and more time in the corner zone (P < 0.05). Compared with the normal control group, the total times for entry into open arms, close arms, and the maze were obviously reduced (P < 0.05), and the proportion of entering open arms was significantly reduced (P < 0.05) in the model group. In TST, the motionless time within the last 4 mm was prolonged in the model group (P < 0.05). The serum cortisol level in the model group was obviously elevated (P < 0.01). CONCLUSION: Social stress induced depression-like animal model in mice of C57BL/6 straineasquite reliable and possibly suitable to be used in integrative medicine research of combination of disease and syndrome model.

Electroacupuncture regulate hypothalamic-pituitary-adrenal axis and enhance hippocampal serotonin system in a rat model of depression.

Hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathogenesis of depression. Dysfunction of the hippocampal serotonin (5-hydroxytryptamine, 5-HT) system has been shown to be a key factor in depression. There is growing evidence that electro-acupuncture (EA) has antidepressant-like effect. However, the effect of EA on HPA axis and hippocampal serotonin system remains unknown. In our study, we investigated the antidepressant-like effect and mechanism of EA for depression rat models. Depression in rats was induced by chronic unpredictable mild stress (CUMS). EA treatment was administered once daily to CUMS rats for 14 days. The acupoints (ST36, bilateral and CV4) were selected. Untreated CUMS rats and normal rats were used as controls. Behavioral tests including forced swim test and open-field test were performed to evaluate the antidepressant effects of EA treatment. Hypothalamic corticotropin-releasing hormone (CRH) mRNA, plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were estimated as indices of HPA axis activity. Enzyme linked immunosorbent assay (ELISA) was performed to determine the concentrations of 5-HT in the hippocampus. Real-time PCR(RT-PCR)and Western blot were respectively used to detect the mRNA and protein levels of 5-hydroxytryptamine 1A receptor (5-HT1AR) in the hippocampus. Our results showed that EA treatment reversed the behavioral deficiency induced by CUMS in rats. EA treatment decreased CRH mRNA expression in the hypothalamic, and ACTH and CORT level in plasma, and markedly increased 5-HT concentration, 5-HT1AR (mRNA and protein) expression in the hippocampus. These results indicated that EA treatment could act on depression by modulating HPA axis and enhancing hippocampal 5-HT/5-HT1AR in CUMS Rats.

Bu-Shen-Yi-Qi formulae suppress chronic airway inflammation and regulate Th17/Treg imbalance in the murine ovalbumin asthma model.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-Shen-Yi-Qi formulae (BSYQF) are frequently used in the treatment of chronic inflammatory diseases in the respiratory system in traditional Chinese medicine (TCM). However, the regulatory effect of BSYQF on T helper 17 (Th17) and regulatory T (Treg) cells in murine ovalbumin (OVA) asthma model remains poorly understood. In the present study, we sought to determine the effect of high-performance liquid chromatography/mass spectrometry (HPLC/MS) standardized BSYQF on chronic airway inflammation and Th17/Treg imbalance in the murine OVA asthma model. MATERIALS AND METHODS: The murine asthma model was induced by OVA sensitization and challenge and BSYQF was oral administrated. 24h after last OVA exposure, airway hyperresponsiveness (AHR) to methacholine (Mch) was assessed, and inflammatory cell counts and classification in bronchoalveolar lavage fluid (BALF) were analysed. Histopathological evaluation of the lung tissue was performed by hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining. Th17 and Treg associated cytokine levels in serum and BALF as well as transcription factors expression in the lung tissue were measured by ELISA, Bio-Plex and western blot assay. We also analysed the CD4(+)RORγt(+) and CD4(+)Foxp3(+) T cells in BALF and spleen by flow cytometric analysis. RESULTS: Our results demonstrated that oral administration of BSYQF inhibited the markedly increased AHR and lung inflammation (p<0.05), resulted in a dramatic reduction in total inflammatory cells as well as neutrophils (Neu), lymphocytes (Lym), monocytes (Mon), eosinophils (Eos) and basophils (Bas) of OVA-induced asthmatic mice (p<0.05). Furthermore, BSYQF treatment caused a distinct reduction in IL-6, IL-10 and IL-17A levels in serum (p<0.05), and induced a significant improvement in IL-6 and IL-10 as well as a marked decrease in TGF-ß1 and IL-17A levels in BALF of OVA-induced asthmatic mice (p<0.05). Mice in BSYQF treated groups also had decreased RORγt and increased Foxp3 expression in the lung tissue (p<0.05). Flow cytometry analysis revealed that CD4(+)RORγt(+) T cells elevated markedly and CD4(+)Foxp3(+) T cells decreased prominently in BALF and spleen in murine OVA asthma model (p<0.05), and BSYQF and DEX treatment lead to an obvious reduction in CD4(+)RORγt(+) T cells in BALF (p<0.05) but not in spleen. BSYQF and DEX treatment resulted in an obvious elevation in CD4(+)Foxp3(+) T cells in BALF and spleen (p<0.05). CONCLUSIONS: Collectively, these results demonstrated that BSYQF could suppress chronic airway inflammation and regulate Th17/Treg imbalance by inhibition of Th17 and enhancement of Treg functions in the murine OVA asthma model, which may help to elucidate the underlying regulatory mode of BSYQF on asthma treatment.

Flavonoid components in Scutellaria baicalensis inhibit nicotine-induced proliferation, metastasis and lung cancer-associated inflammation in vitro.

The objective of the present study was to investigate the therapeutic efficacy of flavonoid components in Scutellaria baicalensis on proliferation, metastasis and lung cancer-associated inflammation during nicotine induction in the A549 and H1299 lung cancer cell lines. After experimental period, augmentation of proliferation was observed, accompanied by marked decrease in apoptotic cells in nicotine-induced lung cancer cells; additionally, nicotine-exposed cells exhibited increased invasive and migratory abilities based on invasion and wound-healing assay. Flavones in Scutellaria, baicalin, baicalein and wogonin significantly counteracted the above deleterious changes. Moreover, assessment of tumor apoptotic and metastatic factors on mRNA levels by quantitative PCR and protein levels by western blotting revealed that these phytochemical treatments effectively negated nicotine-induced upregulated expression of bcl-2, bcl-2/bax ratio, caspase-3, matrix metalloproteinase (MMP)-2 and MMP-9 as well as downregulated expression of bax. Further analysis of inflammatory markers such as tumor necrosis factor (TNF)-α and interleukin (IL)-6 in cell culture supernatant and mRNA and protein expression of nuclear transcription factor-kappaB (NF-κB) and I kappa B-alpha (IκB-α) was carried out to substantiate the anti-inflammatory effect of flavones in Scutellaria in nicotine-exposed lung cancer cells. The therapeutic effects observed in the present study are attributed to the potent potential against proliferation, metastasis and inflammatory microenvironment by flavonoid components in Scutellaria in nicotine-induced lung cancer cells.

Acupuncture treatment of chronic low back pain reverses an abnormal brain default mode network in correlation with clinical pain relief.

BACKGROUND: Acupuncture is gaining in popularity as a treatment for chronic low back pain (cLBP); however, its therapeutic mechanisms remain controversial, partly because of the absence of an objective way of measuring subjective pain. Resting-state functional MRI (rsfMRI) has demonstrated aberrant default mode network (DMN) connectivity in patients with chronic pain, and also shown that acupuncture increases DMN connectivity in pain-modulator and affective-emotional brain regions of healthy subjects. OBJECTIVE: This study sought to explore how cLBP influences the DMN and whether, and how, the altered DMN connectivity is reversed after acupuncture for clinical pain. METHODS: RsfMRI data from 20 patients with cLBP, before and after 4 weeks of treatment, and 10 age- and gender-matched healthy controls (without treatment) were analysed using independent components analyses to determine connectivity within the DMN, and combined with correlation analyses to compute covariance between changes in DMN connectivity and changes in clinical pain. Visual analogue scale data were assessed to rate clinical pain levels. RESULTS: Less connectivity within the DMN was found in patients with cLBP than in healthy controls, mainly in the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate gyrus and precuneus. After acupuncture, patients' connectivities were restored almost to the levels seen in healthy controls. Furthermore, reductions in clinical pain were correlated with increases in DMN connectivity. CONCLUSIONS: This result suggests that modulation of the DMN by acupuncture is related to its therapeutic effects on cLBP. Imaging of the DMN provides an objective method for assessment of the effects of acupuncture-induced analgesia.

[The application of "preventive treatment theory" in chronic airway inflammatory disease].

Bronchial asthma and chronic obstructive pulmonary disease (COPD), as chronic airway inflammatory diseases, seriously threaten the health of human beings. Chinese medicine has obvious advantages in prevention and treatment of them. "Preventive treatment theory" is a sort summarization of preventive medicine in Chinese medicine. The theory is not only reflected at the disease prevention levels, also embodied in the active treatment and the rehabilitation process. It was especially deep and colorfully embodied in the prevention and treatment of chronic airway inflammatory diseases such as asthma and COPD. In this paper,clarified were the prevention and treatment targets, ways of thinking and methods in different stages of asthma and COPD from various viewpoints including prevention before disease occurrence, treating disease at disease onset, preventing the aggravation once disease occurs, and consolidation after disease occurs. We hope to improve ways of thinking and prevention and treatment levels of bronchial asthma and COPD by Chinese medicine.

[An animal model establishment of social stress and its effect evaluation].

OBJECTIVE: To establish a social defeat stress model for simulating the human mental disease, thus laying a foundation for in-depth laboratory research on depression. METHODS: Eight C57BL/6J mice (abbreviated as C57 mice) were recruited as the stress group. They were subject to psychological stress of social defeat for 10 successive days. Besides, another 8 C57 mice were selected as the normal control group (receiving no stress). The Noldus Ethovision was used to evaluate the depressive behavior of mice. The date was acquired in the case of with or without aggressive CD-1 mice in the social defeat open field (SDOF), and it included the two groups of mice's trajectory in the SDOF and the first time of the two groups of mice's entry into the interactive area of the SDOF, the residence time of the two groups of mice in the interactive area of the SDOF, the first time of the two groups of mice's entry into the corner areas of the SDOF and the residence time of the two groups of mice in the corner areas of the SDOF. All data were used to analyze the changes in the behavior of the C57, mice, thus inferring the psychological changes of C57 mice. RESULTS: The mice in the social stress group showed significant behavioral differences when compared with the normal control group. Their trajectories in the interactive area of the SDOF were significantly reduced. The trajectories of the mice in the social stress group were mainly distributed in the corner areas of the SDOF and its surrounding area within the smaller range. The residence time of mice in the social stress group in the interactive area of the SDOF was shortened (P < 0.05). The first time for the mice in the social stress group to enter the interactive area of the SDOF was extended (P < 0.05). Their residence time in the corner areas of the SDOF was shortened (P < 0.05). The first time for mice in the social stress group to enter the corner areas of the SDOF was extended (P < 0.05). CONCLUSION: An animal model of depressive behavior can be established by social defeat stress, which was consistent with human depression.

[Analysis of 'treating different diseases by the same method' from aspect of theoretical research and clinical application of 'replenishing Qi and strengthening Shen'].

Treating different diseases by the same method is one of the most important characteristics in Chinese medicine, and as the main principle of treatment it has been widely applied in Chinese clinics. Its clinical effect is clear. The integration of 'differentiation of diseases' and 'differentiation of syndrome' should be the prerequisite and basis of 'treating different diseases by the same method'. Only if different diseases have the same syndrome, the same treatment can be used on them. Replenishing qi and strengthening Shen is a widely used method that carries out 'treating different diseases by the same method'. It is indicated that the method of 'replenishing qi and strengthening Shen' has preferable effects on many diseases. Part of its mechanism is associated with the improvement of function of neuro-endocrine-immune network, and therefore, it has the clinical effect of 'adjustment of the whole and improvement of the part' on partial disorders. Asthma, chronic obstructive pulmonary disease (COPD), uterine bleeding in puberty, anovulatory infertility, Kidney syndrome and aging, although they are attributed to different diseases and states, only if they have the syndrome of Shen deficiency, the principle of 'treating different diseases by the same method' and the method of 'replenishing qi 'and strengthening Shen' can be used effectively.

Mechanisms Underlying the Antiproliferative and Prodifferentiative Effects of Psoralen on Adult Neural Stem Cells via DNA Microarray.

Adult neural stem cells (NSCs) persist throughout life to replace mature cells that are lost during turnover, disease, or injury. The investigation of NSC creates novel treatments for central nervous system (CNS) injuries and neurodegenerative disorders. The plasticity and reparative potential of NSC are regulated by different factors, which are critical for neurological regenerative medicine research. We investigated the effects of Psoralen, which is the mature fruit of Psoralea corylifolia L., on NSC behaviors and the underlying mechanisms. The self-renewal and proliferation of NSC were examined. We detected neuron- and/or astrocyte-specific markers using immunofluorescence and Western blotting, which could evaluate NSC differentiation. Psoralen treatment significantly inhibited neurosphere formation in a dose-dependent manner. Psoralen treatment increased the expression of the astrocyte-specific marker but decreased neuron-specific marker expression. These results suggested that Psoralen was a differentiation inducer in astrocyte. Differential gene expression following Psoralen treatment was screened using DNA microarray and confirmed by quantitative real-time PCR. Our microarray study demonstrated that Psoralen could effectively regulate the specific gene expression profile of NSC. The genes involved in the classification of cellular differentiation, proliferation, and metabolism, the transcription factors belonging to Ets family, and the hedgehog pathway may be closely related to the regulation.

Establishment and comparison of combining disease and syndrome model of asthma with "kidney yang deficiency" and "abnormal savda".

THE STUDY WAS THE FIRST TIME TO ESTABLISH AND COMPARE TWO RAT MODELS OF TWO COMMON SYNDROMES: Kidney Yang Deficiency syndrome (KYDS) in traditional Chinese medicine (TCM) and abnormal savda syndrome (ASS) in traditional Uighur medicine (TUM). Then, we also established and evaluated rat models of combining disease and syndrome models of asthma with KYDS or ASS. Results showed that usage of the high dose of corticosterone (CORT) injection or external factors could successfully establish the KYDS or ASS rat models, and the two models had similar changes in biological characterization, abnormal behaviors, dysfunction of hypothalamic-pituitary-target organ axes (HPTOA), and sympathetic/parasympathetic (S/P) nerve system but varied in different degrees. The rat models of combining disease and syndrome of asthma with KYDS or ASS had either pathological characteristics of asthma such as airway hyperresponsiveness (AHR), airway inflammation, airway remodeling, which were more serious than allergy exposure alone, or the syndrome performance of Kidney Yang Deficiency in TCM and abnormal savda in TUM. These findings provide a biological rationale for further investigation of combining disease and syndrome model of asthma as an effective animal model for exploring asthma based on the theory of traditional medicine.