Astragaloside IV targeting autophagy of T cells improves inflammation of asthma.

Astragaloside IV (AST) has been confirmed to have antiasthmatic effects. However, the underline mechanism is unclear. The study aimed to explore the treatment mechanism of AST based on autophagy of memory T cells. AST treatment significantly decreased the number of T effector cells in asthma mice blood and the nude mice that received AST-treated TCMs had relieved inflammation compared with the untreated group; meanwhile, we found that AST significantly decreased the autophagy level and inhibited OX40/OX40L signal pathway of lymphocytes. The results highlighted that AST regulated autophagy to inhibit differentiation of effector T-cell phenotype.

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.

Baicalin ameliorates cigarette smoke-induced airway inflammation in rats by modulating HDAC2/NF-κB/PAI-1 signalling.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease distinguished by airway remodelling and progressive inflammation. PAI-1 is an important regulator of fibrosis. Recent studies have shown that PAI-1 seems to be involved in COPD progression. Elevated levels of PAI-1 have been found in the lungs of patients with acute inflammation. PAI-1 has been shown to regulate the levels of proinflammatory cytokines in the lungs, such as tumour necrosis factor (TNF)-α and interleukin (IL)-6, indicating that PAI-1 may play a fundamental role during inflammation. In the present study, we investigated the anti-inflammatory role of baicalin, the main active component of Scutellaria baicalensis, against cigarette smoke (extract) (CS/CSE)-induced airway inflammation in vivo and in vitro. For the in vivo study, SD rats were exposed to CS for 1 h/day, 6 days/week, for 24 weeks and treated with baicalin (40, 80 and 160 mg/kg) or budesonide (0.2 mg/kg). For this study, HBE cells were pretreated with baicalin (10, 20, 40 µM) or dexamethasone (10-7 M) and then exposed to CSE. We found that baicalin treatment could ameliorate CS-induced airway inflammatory infiltration in rats and decrease PAI-1 expression. The ELISA results showed that baicalin significantly inhibited the levels of TNF-α and IL-1ß in CS/CSE-exposed rats and cells. Mechanistic studies showed that baicalin enhanced histone deacetylase 2 (HDAC2) protein expression and inhibited the expression of NF-κB and its downstream target PAI-1, and these effects were reversed by the HDAC2 inhibitor CAY-10683. In conclusion, baicalin ameliorated CS-induced airway inflammation in rats, and these effects were partially attributed to the modulation of HDAC2/NF-κB/PAI-1 signalling.

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.

[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.

Psoralen attenuates cigarette smoke extract-induced inflammation by modulating CD8+ T lymphocyte recruitment and chemokines via the JAK2/STAT1 signaling pathway.

Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Psoralen (PSO) is the main pharmacological component identified from Bu-Shen-Fang-Chuan formula which has been traditionally used in treatment of COPD, yet its efficacy in COPD inflammation were unreported. In this study, we aimed to elucidate the anti-inflammatory potential of PSO in COPD and unravel the underlying mechanisms, focusing on T lymphocyte recruitment and the modulation of chemokines, namely monokine induced by interferon-gamma (CXCL9), interferon inducible protein 10 (CXCL10), and interferon inducible T-Cell alpha chemoattractant (CXCL11). In vitro, RAW264.7 was stimulated by interferon (IFN)-γ + cigarette smoke extract (CSE) and were treated with PSO (2.5, 5, 10 µM), then the levels of chemokines and the activation of Janus kinase (JAK)/Signal transducer and activator of transcription 1 (STAT1) pathway were analyzed by real time PCR and western blot. In vivo, a murine model was established by intraperitoneal injection of CSE on day 1, 8, 15, and 22, then treated with PSO (10 mg/kg). Our experiments in vitro illustrated that PSO reduced the levels of CXCL9, CXCL10, and CXCL11, and decreased the protein phosphorylation levels of JAK2 and STAT1. Additionally, PSO effectively improved inflammatory infiltration and decreased the proportion of CD8+ T cells in CSE-exposed mice. Furthermore, PSO reduced the levels of CXCL9, CXCL10, and CXCL11 in bronchoalveolar lavage fluid (BALF) and lung tissue, and decreased the protein phosphorylation levels of JAK2 and STAT1. In conclusion, our results revealed the therapeutic potential of PSO for COPD inflammation, possibly mediated through the regulation of CD8+ T cell recruitment and chemokines via the JAK2/STAT1 signaling pathway.

Airway inflammation and hypothalamic-pituitary-adrenal axis activity in asthmatic adults with depression.

OBJECTIVE: To investigate the features of airway inflammation and hypothalamic-pituitary-adrenal axis (HPAA) activity in patients with asthma accompanied by depression. METHODS: Adult asthmatics were recruited and enrolled into one of the two groups based on scores on the Hamilton Depression Rating Scale (HAMD): asthmatics with depression (HAMD score ≥8, n = 23), and asthmatics without depression (HAMD score <8, n = 41). In addition, 27 healthy individuals and 21 adults with depression only were enrolled as controls. Induced sputum and blood samples were collected for measurement of cytokines and other inflammatory factors. The diurnal rhythm profiles of salivary cortisol and other hormones were obtained for assessment of the HPAA activity. RESULTS: For the group of asthmatics with depression, the mean HAMD score was 19.0, and for the group of asthmatics without depression, the HAMD score averaged 4.9(p < .001). Serum and sputum tumor necrosis factor alpha (TNF-α) were significantly higher in asthmatics with depression than those in the other groups (p < .05) while serum interferon-gamma (IFN-γ) was lower in asthmatics with depression than that in the other groups (p < .05). Twenty-four-hour urinary cortisol, salivary cortisol at 8 a.m. and 4 p.m. were lower in asthmatics with depression compared to other groups (p < .05). CONCLUSIONS: As compared to healthy individuals and those with asthma or depression alone, individuals with comorbid depression and asthma showed the highest level of pro-inflammatory cytokines and the lowest level of anti-inflammatory cytokines and cortisol. These observations may serve as a valuable reference for diagnosis and clinic therapies of depression in asthmatics.

[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.

Role of cellular senescence in inflammatory lung diseases.

Cellular senescence, a characteristic sign of aging, classically refers to permanent cell proliferation arrest and is a vital contributor to the pathogenesis of cancer and age-related illnesses. A lot of imperative scientific research has shown that senescent cell aggregation and the release of senescence-associated secretory phenotype (SASP) components can cause lung inflammatory diseases as well. In this study, the most recent scientific progress on cellular senescence and phenotypes was reviewed, including their impact on lung inflammation and the contributions of these findings to understanding the underlying mechanisms and clinical relevance of cell and developmental biology. Within a dozen pro-senescent stimuli, the irreparable DNA damage, oxidative stress, and telomere erosion are all crucial in the long-term accumulation of senescent cells, resulting in sustained inflammatory stress activation in the respiratory system. An emerging role for cellular senescence in inflammatory lung diseases was proposed in this review, followed by the identification of the main ambiguities, thus further understanding this event and the potential to control cellular senescence and pro-inflammatory response activation. In addition, novel therapeutic strategies for the modulation of cellular senescence that might help to attenuate inflammatory lung conditions and improve disease outcomes were also presented in this research.

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.

[Effects of acupuncture on default mode network images of chronic sciatica patients in the resting network state].

OBJECTIVE: To observe the functional magnetic resonance imaging (fMRI) data changes of default mode network (DMN) in chronic sciatica patients in the resting network state treated by acupuncture, and to study the correlation between DMN and the consisting effects after acupuncture analgesia. METHODS: Weizhong (BL40) and Huantiao (GB30) of the patients' lower limbs were selected as the main points to acupuncture for ten times. The whole brain was scanned using fMRI. The independent component analysis (ICA) was adopted to get DMN information. The brain DMN function link was analyzed in the two groups of subjects. RESULTS: The DMN images were obtained in all subjects after DMN fMRI data processing. The main DMN differences between the sciatica patients group and the healthy control group were demonstrated as decreased activities of DLPFC and anterior cingulate cortex (ACC). After acupuncture, activities of these regions basically recovered to normal. The DMN of healthy volunteers shown by fMRI data in the RNS mainly existed in the precuneus, BA7, BA10, and ACC. CONCLUSION: MRI images of DMN in the RNS could reflect chronic pain, which was suitable for studies on the effects after acupuncture analgesia.

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.

[Effects of icariin on Bcl-2 and Bax protein expressions and eosinophils apoptosis in bronchial asthmatic mice].

OBJECTIVE: To study the effects of icariin on Bcl-2 and Bax protein expressions and eosinophils apoptosis in bronchial asthmatic mice. METHODS: 48 female Balb/c mice were randomly divided into 6 groups, i.e., the normal control group, the model group, the Dexamethasone group, the low dose icariin group, the middle dose icariin group, and the high dose icariin group, 8 mice in each group. Bronchial asthma in mice were induced by intraperitoneal sensitization and challenged with nebulized ovalbumin (OVA). The mice of each treatment group were administrated with different doses of icariin by peritoneal injection from the first asthma sensitization (the 3rd week after the modeling) to the day before killing once every other day, while mice in the normal control group were administrated with physiological saline. The mice were killed after 6 weeks of treatment. The apoptosis of eosinophils and the Bcl-2 and Bax protein expressions of the lung tissues were detected by TUNEL and immunohistochemical assay respectively. RESULTS: As compared with the model group, the apoptosis ratio of eosinophils were higher in the rest four treatment groups (P<0.05). The Bcl-2 protein positive areas in the lung tissues and the airway wall were significantly lowered (P<0.05). The Bax protein positive area significantly increased (P<0.05). CONCLUSION: In bronchial asthmatic mice, icariin could enhance the apoptosis of eosinophils and lessen their infiltration by decreasing the expression of Bcl-2 protein and increasing the expression of Bax protein in lung.

[Effects of bushen huoxue recipe on urinary levels of albumin, IL-6, TGF-beta1 and MCP-1 in chronic nephritis patients of shen-deficiency blood-stasis syndrome].

OBJECTIVE: To observe the effect of Bushen Huoxue Recipe (BSHXR, a Chinese medicine recipe for Shen reinforcing and blood circulation activating) on the levels of urinary albumin, interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-beta1), and monocyte chemotactic protein-1 (MCP-1) in chronic nephritis patients of Shen-deficiency blood-stasis syndrome. METHODS: Forty-five patients were blocking assigned randomly to two groups, fifteen patients in the control group and thirty in the treatment group. All orally took Monopril 10 mg, once daily. But BSHXR was given additionally to patients in the treatment group after decocting,one dose per day (taken in two times). The treatment course for both groups was eight weeks. Besides, a normal control group consisting of six healthy subjects from health examination of Shuguang Hospital was set up. The 24-h urinary albumin and contents of TGF-beta1, IL-6 and MCP-1 in urine of all subjects were observed. RESULTS: Compared with before treatment the 24-h urinary albumin was obviously reduced in the treatment group, showing significant difference (P<0.01). The urinary 24-h albumin decreased in the control group, with statistical significance (P<0.05). Statistical difference existed between the treatment group and the control group after treatment (P<0.01). Compared with before treatment, urinary levels of IL-6, TGF-beta1, and MCP-1 were all down-regulated in the treatment group and the control group after treatment (P<0.01), and the decreasing of IL-6 and TGF-beta1, levels was more significant in the treatment group statistically (P<0.05). CONCLUSIONS: BSHXR could attenuate the albuminuria in patients of chronic nephritis. Its mechanism might be possibly correlated with its down-regulation of IL-6, TGF-beta1, and MCP-1 levels.

Transcriptomic alterations underline aging of osteogenic bone marrow stromal cells.

BACKGROUND: Multipotent bone marrow stromal cells (BMSCs) are adult stem cells that form functional osteoblasts and play a critical role in bone remodeling. During aging, an increase in bone loss and reduction in structural integrity lead to osteoporosis and result in an increased risk of fracture. We examined age-dependent histological changes in murine vertebrae and uncovered that bone loss begins as early as the age of 1 mo. AIM: To identify the functional alterations and transcriptomic dynamics of BMSCs during early bone loss. METHODS: We collected BMSCs from mice at early to middle ages and compared their self-renewal and differentiation potential. Subsequently, we obtained the transcriptomic profiles of BMSCs at 1 mo, 3 mo, and 7 mo. RESULTS: The colony-forming and osteogenic commitment capacity showed a comparable finding that decreased at the age of 1 mo. The transcriptomic analysis showed the enrichment of osteoblastic regulation genes at 1 mo and loss of osteogenic features at 3 mo. The BMSCs at 7 mo showed enrichment of adipogenic and DNA repair features. Moreover, we demonstrated that the WNT and MAPK signaling pathways were upregulated at 1 mo, followed by increased pro-inflammatory and apoptotic features. CONCLUSION: Our study uncovered the cellular and molecular dynamics of bone aging in mice and demonstrated the contribution of BMSCs to the early stage of age-related bone loss.

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.

[Biomarkers and inflammatory characteristics for microcosmic syndrome differentiation of cold-phlegm syndrome and heat-phlegm syndrome in patients with bronchial asthma].

OBJECTIVE: To explore the biomarkers and inflammatory characteristics for microcosmic syndrome differentiation of cold-phlegm syndrome (CPS) and heat-phlegm syndrome (HPS) in patients with bronchial asthma. METHODS: Patients with bronchial asthma of chronic persistent condition were distributed into three groups according syndrome differentiation, the CPS group (27 patients), the HPS group (32 patients) and the non-cold/heat-phlegm syndrome group (NP group, 31 patients), besides, a control group was setup with 33 healthy persons. Percentages of neutrophils and eosinophils (NEU, EOS) in sputum sample (collected by induction) and peripheral blood were counted; and levels of interleukin-8, -5, and -4 (IL-8, IL-5 and IL-4), interferon-gamma (IFN-gamma), leukotriene B4 (LT-B4), eosinophil cationic protein (ECP), and C-reactive protein (CRP) in sputum supernatant and serum were determined by enzyme-linked immunosorbent assay. RESULTS: Percentage of NEU in sputum of HPS group was higher than that in the other three groups (P < 0.05); while percentages of EOS in serum and sputum of CPS group were higher than that in the other three groups (all P < 0.01). Level of ECP (a parameter closely associated with EOS) also was high in the CPS group, but IL-8 (a parameter closely associated with NEU) showed no significant difference in various groups (P > 0.05). Moreover, the CPS group showed a higher serum IL-4 (P < 0.05) but a lower IFN-gamma/IL-4 level as compared with those in the NP group (P < 0.01). CONCLUSION: Phlegm, which is considered by Chinese medicine as an inveterate root of asthma, might be closely related with the inflammation in modern medicine. The inflammatory characteristics of asthma in patients with CPS partially present as increase of EOS, possibly show Th2 dominant trend, similar to that presented in eosinophilic asthma. Asthma with HPS embodies increase of NEU in respiratory tract. EOS and ECP might be the important markers for microcosmic syndrome differentiation of CPS, and NEU might be that for HPS.