Cytokine Imbalance as a Common Mechanism in Both Psoriasis and Rheumatoid Arthritis.

Psoriasis (PS) and rheumatoid arthritis (RA) are immune-mediated inflammatory diseases. Previous studies showed that these two diseases had a common pathogenesis, but the precise molecular mechanism remains unclear. In this study, RNA sequencing of peripheral blood mononuclear cells was employed to explore both the differentially expressed genes (DEGs) of 10 PS and 10 RA patients compared with those of 10 healthy volunteers and the shared DEGs between these two diseases. Bioinformatics network analysis was used to reveal the connections among the shared DEGs and the corresponding molecular mechanism. In total, 120 and 212 DEGs were identified in PS and RA, respectively, and 31 shared DEGs were identified. Bioinformatics analysis indicated that the cytokine imbalance relevant to key molecules (such as extracellular signal-regulated kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor (TNF), colony-stimulating factor 3 (CSF3), interleukin- (IL-) 6, and interferon gene (IFNG)) and canonical signaling pathways (such as the complement system, antigen presentation, macropinocytosis signaling, nuclear factor-kappa B (NF-κB) signaling, and IL-17 signaling) was responsible for the common comprehensive mechanism of PS and RA. Our findings provide a better understanding of the pathogenesis of PS and RA, suggesting potential strategies for treating and preventing both diseases. This study may also provide a new paradigm for illuminating the common pathogenesis of different diseases.

Differential Amino Acid, Carbohydrate and Lipid Metabolism Perpetuations Involved in a Subtype of Rheumatoid Arthritis with Chinese Medicine Cold Pattern.

Pattern classification is a key approach in Traditional Chinese Medicine (TCM), and it is used to classify the patients for intervention selection accordingly. TCM cold and heat patterns, two main patterns of rheumatoid arthritis (RA) had been explored with systems biology approaches. Different regulations of apoptosis were found to be involved in cold and heat classification in our previous works. For this study, the metabolic profiling of plasma was explored in RA patients with typical TCM cold or heat patterns by integrating liquid chromatography/mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS) platforms in conjunction with the Ingenuity Pathway Analysis (IPA) software. Three main processes of metabolism, including amino acid, carbohydrate and lipid were focused on for function analysis. The results showed that 29 and 19 differential metabolites were found in cold and heat patterns respectively, compared with healthy controls. The perturbation of amino acid metabolism (increased essential amino acids), carbohydrate metabolism (galactose metabolism) and lipid metabolism, were found to be involved in both cold and heat pattern RA. In particular, more metabolic perturbations in protein and collagen breakdown, decreased glycolytic activity and aerobic oxidation, and increased energy utilization associated with RA cold pattern patients. These findings may be useful for obtaining a better understanding of RA pathogenesis and for achieving a better efficacy in RA clinical practice.

The Potential Biomarkers to Identify the Development of Steatosis in Hyperuricemia.

Hyperuricemia (HU) often progresses to combine with non-alcoholic fatty liver disease (NAFLD) in the clinical scenario, which further exacerbates metabolic disorders; early detection of biomarkers, if obtained during the HU progression, may be beneficial for preventing its combination with NAFLD. This study aimed to decipher the biomarkers and mechanisms of the development of steatosis in HU. Four groups of subjects undergoing health screening, including healthy subjects, subjects with HU, subjects with HU combined with NAFLD (HU+NAFLD) and subjects with HU initially and then with HU+NAFLD one year later (HU→HU+NAFLD), were recruited in this study. The metabolic profiles of all subjects' serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry. The metabolomic data from subjects with HU and HU+NAFLD were compared, and the biomarkers for the progression from HU to HU+NAFLD were predicted. The metabolomic data from HU→HU+NAFLD subjects were collected for further verification. The results showed that the progression was associated with disturbances of phospholipase metabolism, purine nucleotide degradation and Liver X receptor/retinoic X receptor activation as characterized by up-regulated phosphatidic acid, cholesterol ester (18:0) and down-regulated inosine. These metabolic alterations may be at least partially responsible for the development of steatosis in HU. This study provides a new paradigm for better understanding and further prevention of disease progression.

Molecular mechanism of inhibition of the abnormal proliferation of human umbilical vein endothelial cells by hydroxysafflor-yellow A.

Context It has been found that hydroxysafflor-yellow A (HSYA) inhibits angiogenesis and the proliferation of abnormal human umbilical vein endothelial cells (HUVECs) in our previous study; however, the mechanism is still unclear. Objective This study investigates the mechanisms of HSYA inhibiting abnormal proliferation of HUVECs through detecting the expression of vascular endothelial growth factor (VEGF) and its receptor (KDR), and the protein expression in the Ras-Raf-MEK-ERK-signalling pathway. Materials and methods HepG2 cell cultural supernatant was used to culture HUVECs to make promote abnormal proliferation, and HSYA was added into the medium. The expression of VEGF, KDR, c-myc, N-ras and NF-κB1 in abnormal HUVEC was detected by RT-qPCR and ELISA at the mRNA and protein levels. Protein expression of ERK signal pathway was measured by Western blot. Results Compared with the abnormal proliferation of HUVECs without any treatment, HSYA inhibited the expression of VEGF and KDR in vitro. Similarly, the protein expression of Ras, p-raf, p-ERK and p-p38MARK in the abnormal HUVECs was reduced when they were treated by HSYA, especially in p-ERK, yet the total raf, ERK, p38MAPK and Akt were not changed whether HSYA existed or not. HSYA could also inhibit the expression of c-myc, N-ras, and NF-κB1. Conclusion When the abnormal HUVECs were treated with HSYA, the low expression of VEGF and KDR reduced the expression of oncogene and transcription factor through the Ras-Raf-MEK-ERK1/2 pathway of the MAPK family. This resulted in inhibiting the abnormal proliferation of HUVECs and angiogenesis.

The Crosstalk of Pathways Involved in Immune Response Maybe the Shared Molecular Basis of Rheumatoid Arthritis and Type 2 Diabetes.

Rheumatoid arthritis (RA) and Type 2 diabetes (T2D) are both systemic diseases linked with altered immune response, moderate mortality when present together. The treatment for both RA and T2D are not satisfied, partly because of the linkage between them has not yet been appreciated. A comprehensive study for the potential associations between the two disorders is needed. In this study, we used RNA sequencing to explore the differently expressed genes (DEGs) in peripheral blood mononuclear cells (PBMC) of 10 RA and 10 T2D patients comparing with 10 healthy volunteers (control). We used bioinformatics analysis and the Ingenuity Pathways Analysis (IPA) to predict the commonalities on signaling pathways and molecular networks between those two diseases. 212 DEGs in RA and 114 DEGs in T2D patients were identified compared with healthy controls, respectively. 32 DEGs were shared between the two comparisons. The top 10 shared pathways interacted in cross-talking networks, regulated by 5 shared predicted upstream regulators, leading to the activated immune response were explored, which was considered as partly of the association mechanism of this two disorders. These discoveries would be considered as new understanding on the associations between RA and T2D, and provide novel treatment or prevention strategy.

Molecular network-based analysis of guizhi-shaoyao-zhimu decoction, a TCM herbal formula, for treatment of diabetic peripheral neuropathy.

AIM: Guizhi-shaoyao-zhimu decoction (GSZ), a traditional Chinese medicine (TCM) herbal formula, has been shown effective in the treatment of diabetic peripheral neuropathy (DPN). In this study, network analysis was performed to decipher the molecular mechanisms of GSZ in the treatment of DPN. METHODS: The chemical components of the 3 herbs forming GSZ, ie, Ramulus Cinnamomi (Guizhi), Paeonia lactiflora (Shaoyao) and Rhizoma Anemarrhenae (Zhimu), were searched in Chinese medicine dictionaries, and their target proteins were identified in PubChem. DPN genes were searched in PubMed gene databases. Ingenuity Pathway Analysis (IPA) was used to build the GSZ pharmacological network and DPN molecular network. The canonical pathways between the two networks were compared to decipher the molecular mechanisms of GSZ in the treatment of DPN. RESULTS: Sixty-one protein targets for Guizhi, 31 targets for Shaoyao, 47 targets for Zhimu, as well as 23 genes related to DPN were identified and uploaded to IPA. The primary functions of the DPN molecular network were inflammatory response, metabolic disease, cellular assembly and organization. As far as the pharmacological network functions were concerned, Guizhi target proteins were involved in neurological disease, inflammatory disease, cellular growth and proliferation, cell signaling, molecular transport, and nucleic acid metabolism, Shaoyao target proteins were related to neurological disease, inflammatory disease, and Zhimu target proteins focused on cell death and survival, cellular movement, immune cell trafficking, DNA replication, recombination and repair, and cell cycle. In the three-herb combination GSZ, several new network functions were revealed, including the inflammatory response, gene expression, connective tissue development and function, endocrine system disorders, and metabolic disease. The canonical pathway comparison showed that Shaoyao focused on IL-12 signaling and production in macrophages, and Zhimu focused on TNFR2 signaling, death receptor signaling, ILK signaling, IL-17A in gastric cells, IL-6 signaling, IL-8 signaling, the role of JAK1, JAK2, and TYK2 in interferon signaling, IL-9 signaling, HMGB1 signaling, NO production and ROS production in macrophages, whereas GSZ focused aryl hydrocarbon receptor signaling and apoptosis signaling in addition to those pathways induced by Guizhi, Shaoyao and Zhimu. CONCLUSION: Although each single herb can affect some DPN-related functions and pathways, GSZ exerts more effects on DPN-related functions and pathways. The effects of GSZ on aryl hydrocarbon receptor signaling and apoptosis signaling pathways may be the key components of its total molecular mechanisms.

Lipidomic-based investigation into the regulatory effect of Schisandrin B on palmitic acid level in non-alcoholic steatotic livers.

Schisandrin B (SchB) is one of the most abundant bioactive dibenzocyclooctadiene derivatives found in the fruit of Schisandra chinensis. Here, we investigated the potential therapeutic effects of SchB on non-alcoholic fatty-liver disease (NAFLD). In lipidomic study, ingenuity pathway analysis highlighted palmitate biosynthesis metabolic pathway in the liver samples of SchB-treated high-fat-diet-fed mice. Further experiments showed that the SchB treatment reduced expression and activity of fatty acid synthase, expressions of hepatic mature sterol regulatory element binding protein-1 and tumor necrosis factor-α, and hepatic level of palmitic acid which is known to promote progression of steatosis to steatohepatitis. Furthermore, the treatment also reduced hepatic fibrosis, activated nuclear factor-erythroid-2-related factor-2 which is known to attenuate the progression of NASH-related fibrosis. Interestingly, in fasting mice, a single high-dose SchB induced transient lipolysis and increased the expressions of adipose triglyceride lipase and phospho-hormone sensitive lipase. The treatment also increased plasma cholesterol levels and 3-hydroxy-3-methylglutaryl-CoA reductase activity, reduced the hepatic low-density-lipoprotein receptor expression in these mice. Our data not only suggest SchB is a potential therapeutic agent for NAFLD, but also provided important information for a safe consumption of SchB because SchB overdosed under fasting condition will have adverse effects on lipid metabolism.

Predicting and verifying outcome of Tripterygium wilfordii Hook F. based therapy in rheumatoid arthritis: from open to double-blinded randomized trial.

Tripterygium wilfordii Hook F. (TwHF) based therapy has been proved as effective in treating rheumatoid arthritis (RA), yet the predictors to its response remains unclear. A two-stage trial was designed to identify and verify the baseline symptomatic predictors of this therapy. 167 patients with active RA were enrolled with a 24-week TwHF based therapy treatment and the symptomatic predictors were identified in an open trial; then in a randomized clinical trial (RCT) for verification, 218 RA patients were enrolled and classified into predictor positive (P+) and predictor negative (P-) group, and were randomly assigned to accept the TwHF based therapy and Methotrexate and Sulfasalazine combination therapy (M) for 24 weeks, respectively. Five predictors were identified (diuresis, excessive sweating, night sweats for positive; and yellow tongue-coating, thermalgia in the joints for negative). In the RCT, The ACR 20 responses were 82.61% in TwHF/P+ group, significantly higher than that in TwHF/P- group (P = 0.0001) and in M&S/P+ group (P < 0.05), but not higher than in M&S/P- group. Similar results were yielded in ACR 50 yet not in ACR 70 response. No significant differences were detected in safety profiles among groups. The identified predictors enable the TwHF based therapy more efficiently in treating RA subpopulations.

Effect of curcumin on aged Drosophila melanogaster: a pathway prediction analysis.

OBJECTIVE: To re-analyze the data published in order to explore plausible biological pathways that can be used to explain the anti-aging effect of curcumin. METHODS: Microarray data generated from other study aiming to investigate effect of curcumin on extending lifespan of Drosophila melanogaster were further used for pathway prediction analysis. The differentially expressed genes were identified by using GeneSpring GX with a criterion of 3.0-fold change. Two Cytoscape plugins including BisoGenet and molecular complex detection (MCODE) were used to establish the protein-protein interaction (PPI) network based upon differential genes in order to detect highly connected regions. The function annotation clustering tool of Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for pathway analysis. RESULTS: A total of 87 genes expressed differentially in D. melanogaster melanogaster treated with curcumin were identified, among which 50 were up-regulated significantly and 37 were remarkably down-regulated in D. melanogaster melanogaster treated with curcumin. Based upon these differential genes, PPI network was constructed with 1,082 nodes and 2,412 edges. Five highly connected regions in PPI networks were detected by MCODE algorithm, suggesting anti-aging effect of curcumin may be underlined through five different pathways including Notch signaling pathway, basal transcription factors, cell cycle regulation, ribosome, Wnt signaling pathway, and p53 pathway. CONCLUSION: Genes and their associated pathways in D. melanogaster melanogaster treated with anti-aging agent curcumin were identified using PPI network and MCODE algorithm, suggesting that curcumin may be developed as an alternative therapeutic medicine for treating aging-associated diseases.

The shared crosstalk of multiple pathways involved in the inflammation between rheumatoid arthritis and coronary artery disease based on a digital gene expression profile.

Rheumatoid arthritis (RA) and coronary artery disease (CAD) are both complex inflammatory diseases, and an increased prevalence of CAD and a high rate of mortality have been observed in RA patients. But the molecular mechanism of inflammation that is shared between the two disorders is unclear. High-throughput techniques, such as transcriptome analysis, are becoming important tools for genetic biomarker discovery in highly complex biological samples, which is critical for the diagnosis, prognosis, and treatment of disease. In the present study, we reported one type of transcriptome analysis method: digital gene expression profiling of peripheral blood mononuclear cells of 10 RA patients, 10 CAD patients and 10 healthy people. In all, 213 and 152 differently expressed genes (DEGs) were identified in RA patients compared with normal controls (RA vs. normal) and CAD patients compared with normal controls (CAD vs. normal), respectively, with 73 shared DEGs between them. Using this technique in combination with Ingenuity Pathways Analysis software, the effects on inflammation of four shared canonical pathways, three shared activated predicted upstream regulators and three shared molecular interaction networks were identified and explored. These shared molecular mechanisms may provide the genetic basis and potential targets for optimizing the application of current drugs to more effectively treat these diseases simultaneously and for preventing one when the other is diagnosed.

Serum metabolomics reveals betaine and phosphatidylcholine as potential biomarkers for the toxic responses of processed Aconitum carmichaelii Debx.

We recently reported that processed Aconitum carmichaelii Debx (Bai-Fu-Pian in Chinese, BFP) elicits differential toxic responses in rats under various health conditions. The present study aimed to determine the graded toxicity of BFP so as to derive a safe therapeutic rationale in clinical practice. Sensitive and reliable biomarkers of toxicity were also identified, with the corresponding metabolic pathways being unveiled. Thirty male Sprague-Dawley rats were divided into five groups (n = 6) and received oral administration of BFP extract (0.32, 0.64, 1.28 or 2.56 g kg(-1) per day) or an equal volume of drinking water (control) for 15 days. The metabolomic profiles of rat serum were analyzed by liquid chromatography quadruple time-of-flight mass spectrometry (LC-Q-TOF-MS). Linear regression analysis and Ingenuity Pathway Analysis (IPA) were used to elucidate the differentiated altered metabolites and associated network relationships. Results from biochemical and histopathological examinations revealed that BFP could induce prominent toxicity in the heart, liver and kidneys at a dose of 2.56 g kg(-1) per day. Betaine up-regulation and phosphatidylcholine down-regulation were detected in the serum samples of drug-treated groups in a dose-dependent manner. In summary, betaine and phosphatidylcholine could be regarded as sensitive biomarkers for the toxic responses of BFP. Perturbations of RhoA signaling, choline metabolism and free radical scavenging were found to be partly responsible for the toxic effects of the herbal drug. Based on the metabolomics findings, we could establish a safe therapeutic range in the clinical use of BFP, with promising predictions of possible drug toxicity.

Ginsenoside Rg1 reduces toxicity of fine particulate matter on human alveolar epithelial cells: a preliminary observation.

Fine particulate matter (PM2.5) is a significant environmental pollutant responsible for a number of human diseases. Ginsenoside Rg1 (Rg1) is likely to have the potential to relieve PM2.5­induced cell injury. The present study is designed to preliminarily observe the harmful effect of PM2.5 and the protective effect of Rg1 against PM2.5 on human A549 lung epithelial cells in vitro. The cytotoxic effects of the PM2.5 or Rg1 on A549 cells were measured by means of cell viability, and then exposure concentration of PM2.5 and pretreatment concentration of Rg1 used in the following assays were established. The A549 cells were pretreated with Rg1 for 1 h and then exposed to PM2.5 for 24 h. The levels of lactate dehydrogenase (LDH) in the cell culture supernatant and malondialdehyde (MDA) within the cells were assayed. The present results revealed that 200­1,200 µg/ml of PM2.5 decreased the viability of A549 cells significantly in a concentration­dependent manner; however, 50­400 µg/ml of Rg1 had no significant effect. Pretreatment with 100, 200 or 400 µg/ml Rg1 significantly diminished the 200 µg/ml PM2.5­induced A549 cell viability and decreased LDH leakage and MDA generation in a concentration­dependent manner. These results indicated that PM2.5 induced cell injury and Rg1, antagonized PM2.5­induced cell injury to a certain extent.

Rheumatoid arthritis with deficiency pattern in traditional chinese medicine shows correlation with cold and hot patterns in gene expression profiles.

In our precious study, the correlation between cold and hot patterns in traditional Chinese medicine (TCM) and gene expression profiles in rheumatoid arthritis (RA) has been explored. Based on TCM theory, deficiency pattern is another key pattern diagnosis among RA patients, which leads to a specific treatment principle in clinical management. Therefore, a further analysis was performed aiming at exploring the characteristic gene expression profile of deficiency pattern and its correlation with cold and hot patterns in RA patients by bioinformatics analysis approach based on gene expression profiles data detected with microarray technology. The TCM deficiency pattern-related genes network comprises 7 significantly, highly connected regions which are mainly involved in protein transcription processes, protein ubiquitination, toll-like receptor activated NF- κ B regulated gene transcription and apoptosis, RNA clipping, NF- κ B signal, nucleotide metabolism-related apoptosis, and immune response processes. Toll-like receptor activated NF- κ B regulated gene transcription and apoptosis pathways are potential specific pathways related to TCM deficiency patterns in RA patients; TCM deficiency pattern is probably related to immune response. Network analysis can be used as a powerful tool for detecting the characteristic mechanism related to specific TCM pattern and the correlations between different patterns.

Serum metabolic signatures of four types of human arthritis.

Similar symptoms of the different types of arthritis have continued to confound the clinical diagnosis and represent a clinical dilemma making treatment choices with a more personalized or generalized approach. Here we report a mass spectrometry-based metabolic phenotyping study to identify the global metabolic defects associated with arthritis as well as metabolic signatures of four major types of arthritis--rheumatoid arthritis (n = 27), osteoarthritis (n = 27), ankylosing spondylitis (n = 27), and gout (n = 33)--compared with healthy control subjects (n = 60). A total of 196 metabolites were identified from serum samples using a combined gas chromatography coupled with time-of-flight mass spectrometry (GC-TOF MS) and ultraperformance liquid chromatography quadrupole-time-of-flight mass spectrometry (UPLC-QTOF MS). A global metabolic profile is identified from all arthritic patients, suggesting that there are common metabolic defects resulting from joint inflammation and lesion. Meanwhile, differentially expressed serum metabolites are identified constituting an unique metabolic signature of each type of arthritis that can be used as biomarkers for diagnosis and patient stratification. The results highlight the applicability of metabonomic phenotyping as a novel diagnostic tool for arthritis complementary to existing clinical modalities.

Molecular network and chemical fragment-based characteristics of medicinal herbs with cold and hot properties from Chinese medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Chinese herbal medicines (HMs) is one of the great herbal systems of the world, which play an important role in current health care system in many countries. In the view of tradition Chinese medicine (TCM) theory, Yin-yang and five-elements theory is the central theory, which is used to explain how the world and body work. Under the guidance of such philosophy, TCM considers that HMs have different properties, which are the important factors for prescribing herbal formulae; such prescriptions are based on TCM pattern classification in clinical practice. The cold and hot property are commonly defined for HM property identification; however, the biological activities that are related to the HM property remain a mystery because of a lack of appropriate methods. A bioinformatics approach was applied to identify the distinguishing biological activities of HMs that have these cold and hot properties. MATERIAL AND METHODS: Twenty HMs with typical cold and hot properties (10 cold and 10 hot) were selected based on TCM clinical application records and Chinese pharmacopeia. The active target proteins of each HM were searched in the PubChem database and were analyzed in Ingenuity Pathway Analysis (IPA) platform to find out the HM property-related biological activities. In addition, the main compounds of the HMs were fragmented using a fragment-based approach and were analyzed for the purpose of deciphering the properties. RESULTS: The main biological networks of HMs with cold and hot properties include cell cycle, cellular growth, proliferation and development, cancer, cytokine signaling, and intracellular and second messenger signaling; 11 specific pathways are presented to be perturbed only by HMs with the hot property, and the 27 specific target protein molecules include PRKACA, PRKCA, PRKCB, PRKCD, PRKCE, PRKCG, PRKD1, TLR4, TLR7, TLR8, TLR9, HTR4, HTR6, HTR7, HTR2A, HTR1B, HTR2B, GNAO1, GNAI1, TNF, IL8, ROCK2, AKT1, MAPK1, RPS6KA1, RPS6KA3 and JAK2, which are involved in the biological network. One specific pathway is detected to be involved in the biological network of HMs with the cold property, the specific molecules are RAN and KPNB1. Cold propertied HMs show intensive toxicity in the heart, liver and kidney compared with hot HMs, which is likely to be correlated with the specific chemical fragments constructions in the HMs with the cold property, such as long chain alkenes, Benzo heterocycle and azotic heterocycle according to the chemical fragment analysis for the HMs. CONCLUSIONS: Inflammation and immunity regulation are more related to HMs with the hot property, and cold propertied HMs possess the tendency to impact cell growth, proliferation and development. Integrative bioinformatics analysis and chemical structure analysis are a promising methods for identifying the biological activity of HM properties.

Deciphering the differential toxic responses of Radix aconiti lateralis praeparata in healthy and hydrocortisone-pretreated rats based on serum metabolic profiles.

Radix aconiti lateralis praeparata (Baifupian) has received great attention because of its excellent therapeutic effects as well as the associated adverse drug reactions. According to the traditional Chinese medicine (TCM) principle, Baifupian should only be used in patients with TCM "kidney-yang" deficiency pattern, a clinical state that can be mimicked by hydrocortisone induction in rats. This study aimed to decipher the differential toxic responses of Baifupian in healthy and hydrocortisone-pretreated rats based on serum metabolic profiles. Drug-treated rats received Baifupian intragastrically at the dose of 1.28 g/kg/day for 15 days. Serum metabolic profiles were obtained by using the LC-Q-TOF-MS technique. Our results show that Baifupian could induce severe toxicity in the heart, liver, and kidneys of healthy rats. These drug-induced toxic reactions were largely alleviated in hydrocortisone-pretreated animals. Changes of metabolic profiles in drug-treated healthy and hydrocortisone-pretreated rats were demonstrated, involving oxidative phosphorylation, amino acid and lipid metabolism as characterized by altered phosphate, betaine, and phosphatidyl choline. These metabolic alterations could be responsible at least in part for the differential toxic responses of Baifupian under various health conditions. This study provides a new paradigm for better understanding of the risks and limitations when using potentially toxic herbs in clinical applications.

Understanding the molecular mechanism of interventions in treating rheumatoid arthritis patients with corresponding traditional chinese medicine patterns based on bioinformatics approach.

Better effectiveness would be achieved when interventions are used in treating patients with a specific traditional Chinese medicine (TCM) pattern. In this paper, the effectiveness in treating rheumatoid arthritis (RA) patients in a randomized clinical trial as reanalyzed after the patients were classified into different TCM patterns and the underlying mechanism of how the TCM pattern influences the clinical effectiveness of interventions (TCM and biomedicine therapy) was explored. The pharmacological networks of interventions were builtup with protein and protein interaction analyses based on all the related targeted proteins obtained from PubChem. The underlying mechanism was explored by merging the pharmacological networks with the molecular networks of TCM cold and hot patterns in RA. The results show that the TCM therapy is better in treating the RA patients with TCM hot pattern, and the biomedical therapy is better in the RA patients with cold pattern. The pharmacological network of TCM intervention is merged well with the molecular network of TCM hot pattern, and the pharmacological network of biomedical therapy is merged well with the network of cold pattern. The finding indicates that molecular network analysis could give insight into the full understanding of the underlying mechanism of how TCM pattern impacts the efficacy.

The effect of curcumin on human bronchial epithelial cells exposed to fine particulate matter: a predictive analysis.

Fine particulate matter (PM2.5) has been associated in humans with inflammation, oxidative stress and cancer. Studies had shown that curcumin could potentially inhibit these effects; however, there had been no in vivo or in vitro reports about the effects of curcumin on organisms exposed to PM2.5. This predictive study explored the possible biological functions and pathways involved in the mechanism of curcumin inhibition of the hazardous effects of PM2.5. For predictive analysis, microarray data were used to investigate the effect of PM2.5 on human bronchial epithelial cells (HBEC), and human target proteins of curcumin were retrieved from PubChem. Two protein-protein interaction (PPI) networks were established based upon differential genes and target proteins, respectively, and the common network of these two networks was found. Functional and pathway analysis of the common network was performed using the Ingenuity Pathways Analysis (IPA) software. The results suggested that the predictive effects of curcumin on HBEC exposed to PM2.5 were involved in bio-functions, including inflammatory response of airway, cancerogenesis, and apoptosis, and in pathways such as cancer, glucocorticoid receptor signaling, and NF-kappaB signaling. This study predicted for the first time that curcumin could be a potential therapeutic agent for protecting the human airway from the hazardous effects of PM2.5.

Maturation of murine bone marrow-derived dendritic cells induced by Radix Glycyrrhizae polysaccharide.

Radix Glycyrrhizae polysaccharide (GP), the most important component of Radix Glycyrrhizae, has been reported to have many immunopharmacological activities. However, the mechanism by which GP affects dendritic cells (DCs) has not been elucidated. In this study, we investigated the effect of GP on murine bone marrow-derived DCs and the potential pathway through which GP exerts this effect. Mononuclear cells (MNCs) were isolated from murine bone marrow and induced to become DCs by culturing with GM-CSF and IL-4. Six days later, DCs were divided into three groups: control group, GP group and LPS group. After 48 h of treatment, phenotypic figures and antigen uptake ability were determined by FACS analysis. The proliferation of DC-stimulated allogenic CD3+ T cells was detected by WST-1. IL-12 p70 and IFN-γ, which are secreted by DCs and CD3+ T cells respectively, were quantified by ELISA. Additionally, IL-12 p40 mRNA expression was determined by real-time PCR. Alterations in TLR4-related signaling pathways were examined by performing an antibody neutralization experiment. Treatment of DCs with GP resulted in the enhanced expression of the cell surface molecules CD80, CD86 and MHC I-A/I-E. GP also increased the production of IL-12 p70 by DCs in a time-dependent manner. The endocytosis of FITC-dextran by DCs was suppressed by GP administration. Furthermore, GP-treated DCs enhanced both the proliferation and IFN-γ secretion of allogenic CD3+ T cells. Finally, the effects of GP on DCs were partially reduced by using inhibitors of TLR4, NF-κB, p38 MAPK or JNK. In conclusion, GP can induce the maturation of DCs, and does so, in part, by regulating a TLR4-related signaling pathway.