Anti-Allergic Inflammatory Activity of Interleukin-37 Is Mediated by Novel Signaling Cascades in Human Eosinophils

IL-1 family regulatory cytokine IL-37b can suppress innate immunity and inflammatory activity in inflammatory diseases. In this study, IL-37b showed remarkable in vitro suppression of inflammatory tumor necrosis factor-α, IL-1β, IL-6, CCL2, and CXCL8 production in the coculture of human primary eosinophils and human bronchial epithelial BEAS-2B cells with the stimulation of bacterial toll-like receptor-2 ligand peptidoglycan, while antagonizing the activation of intracellular nuclear factor-κB, PI3K–Akt, extracellular signal-regulated kinase 1/2, and suppressing the gene transcription of allergic inflammation-related PYCARD, S100A9, and CAMP as demonstrated by flow cytometry, RNA-sequencing, and bioinformatics. Results therefore elucidated the novel anti-inflammation-related molecular mechanisms mediated by IL-37b. Using the house dust mite (HDM)-induced humanized asthmatic NOD/SCID mice for preclinical study, intravenous administration of IL-37b restored the normal plasma levels of eosinophil activators CCL11 and IL-5, suppressed the elevated concentrations of Th2 and asthma-related cytokines IL-4, IL-6, and IL-13 and inflammatory IL-17, CCL5, and CCL11 in lung homogenate of asthmatic mice. Histopathological results of lung tissue illustrated that IL-37b could mitigate the enhanced mucus, eosinophil infiltration, thickened airway wall, and goblet cells. Together with similar findings using the ovalbumin- and HDM-induced allergic asthmatic mice further validated the therapeutic potential of IL-37b in allergic asthma. The above results illustrate the novel IL-37-mediated regulation of intracellular inflammation mechanism linking bacterial infection and the activation of human eosinophils and confirm the in vivo anti-inflammatory activity of IL-37b on human allergic asthma

Actein Inhibits the Proliferation and Adhesion of Human Breast Cancer Cells and Suppresses Migration in vivo

Background and purpose: Metastasis is an important cause of death in breast cancer patients. Anti-metastatic agents are urgently needed since standard chemotherapeutics cannot diminish the metastatic rate. Actein, a cycloartane triterpenoid, has been demonstrated to exhibit anti-angiogenic and anti-cancer activities. Its anti-metastatic activity and underlying mechanisms were evaluated in the present study.Methods: The effects of actein on the proliferation, cell cycle phase distribution, migration, motility and adhesion were evaluated using two human breast cancer cell lines, MDA-MB-231 (estrogen receptor-negative) and MCF-7 cells (estrogen receptor-positive) in vitro. Western blots and real-time PCR were employed to examine the protein and mRNA expression of relevant signaling pathways. A human metastatic breast cancer cell xenograft model was established in transparent zebrafish embryos to examine the anti-migration effect of actein in vivo.Results:In vitro results showed that actein treatment significantly decreased cell proliferation, migration and motility. Furthermore, actein significantly caused G1 phase cell cycle arrest and suppressed the protein expression of matrix metalloproteinases of MDA-MB-231 cells. In addition, actein inhibited breast cancer cell adhesion to collagen, also reduced the expression of integrins. Actein treatment down-regulated the protein expression of epidermal growth factor receptor (EGFR), AKT and NF-κB signaling proteins. In vivo results demonstrated that actein (60 μM) significantly decreased the number of zebrafish embryos with migrated cells by 74% and reduced the number of migrated cells in embryos.Conclusion: Actein exhibited anti-proliferative, anti-adhesion and anti-migration activities, with the underlying mechanisms involved the EGFR/AKT and NF-kappaB signalings. These findings shed light for the development of actein as novel anti-migration natural compound for advanced breast cancer

Effects of Spray-Drying and Choice of Solid Carriers on Concentrations of Labrasol ® and Transcutol ® in Solid Self-Microemulsifying Drug Delivery Systems (SMEDDS)

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The Diagnostic Utility of Cardiac Biomarkers in Dialysis Patients

Mortality in dialysis patients remains high due to excessive cardiovascular disease burden from coronary artery disease, left ventricular hypertrophy, and heart failure. Thus, cardiovascular risk stratification is an important aspect in managing dialysis patients; it may enable early identification of high-risk patients to optimize therapeutic interventions that may ultimately lower their cardiovascular morbidity and mortality. In particular, serum cardiac biomarkers that are readily measured, inexpensive, reproducible with high sensitivity and specificity, may have potential for cardiovascular risk prediction and stratification. Cardiac troponin represents a highly sensitive and specific marker of myocardial damage and is a current gold standard test for diagnosing acute myocardial infarction in the general population. On the other hand, natriuretic peptides, released from the heart secondary to increased left ventricular wall stress, have emerged as a diagnostic marker for heart failure in the general population. These two biomarkers reflect unique pathology of the myocardium and are powerful prognostic markers in the dialysis population. This article reviews the diagnostic potentials of these two cardiac biomarkers and their clinical application in the dialysis population. © 2012 Wiley Periodicals, Inc.Link_to_subscribed_fulltex

Natural Products from Chinese Medicines with Potential Benefits to Bone Health

Osteoporosis is a progressive, systemic bone disorder characterized by loss of bone mass and microstructure, leading to reduced bone strength and increased risk of fracture. It is often associated with reduced quality of life and other medical complications. The disease is common in the aging population, particularly among postmenopausal women and patients who receive long-term steroidal therapy. Given the rapid growth of the aging population, increasing life expectancy, the prevalence of bone loss, and financial burden to the healthcare system and individuals, demand for new therapeutic agents and nutritional supplements for the management and promotion of bone health is pressing. With the advent of global interest in complementary and alternative medicine and natural products, Chinese medicine serves as a viable source to offer benefits for the improvement and maintenance of bone health. This review summarizes the scientific information obtained from recent literatures on the chemical ingredients of Chinese medicinal plants that have been reported to possess osteoprotective and related properties in cell-based and/or animal models. Some of these natural products (or their derivatives) may become promising leads for development into dietary supplements or therapeutic drugs

IS THERE A LINK BETWEEN SUNLIGHT EXPOSURE AND 25-HYDROXYVITAMIN D DEFICIENCY IN CHRONIC KIDNEY DISEASE PATIENTS?

There is an increasing global recognition of nutritional vitamin D deficiency in patients with chronic kidney disease (CKD). Yet, there is not much data in the Chinese population. We performed this prospective cross-sectional survey, with an aim to determine the prevalence of vitamin D deficiency (defined as serum 25-hydroxyvitamin D [25(OH)D] level <30ng/mL) in a cohort of Chinese stage 3-5 CKD patients and factors associated with its deficiency. Two-hundred and fifty (157 men and 93 women) stage 3-5 CKD patients (mean age: 57±12 years) were invited to have blood taking for 25(OH)D levels and other biochemical parameters and were asked to record the average number of hours of outdoor sunlight exposure per day during weekday and weekend in the week before blood taking. The mean glomerular filtration rate (GFR) estimated by the MDRD equation was 25±13 ml/min per 1.73m2, with 84, 91 and 75 patients having stage 3, 4 and 5 CKD. Two hundred and twenty-six patients (90%) were confirmed to be 25(OH)D deficient with 97% of the women having 25(OH)D deficiency as compared to 87% of men. In the univariate analysis, both weekday and weekend outdoor sunlight exposure showed significant positive association with serum 25(OH)D levels. In the multiple linear regression analysis, younger age (P<0.001), fewer weekday sun exposure hours (P<0.001) and female gender (P=0.001) were found to be the most significant factors associated with lower serum 25(OH)D levels. In conclusion, our study confirmed an extremely high prevalence of vitamin D deficiency and an important association between outdoor sunlight exposure and 25(OH)D deficiency in Chinese stage 3-5 CKD patients. Further study is needed to determine whether increasing daily outdoor sunlight exposure may represent a cost-free treatment for correcting nutritional 25(OH)D deficiency in the CKD population

Effect of Tumor Necrosis Factor Family Member LIGHT (TNFSF14) on the Activation of Basophils and Eosinophils Interacting with Bronchial Epithelial Cells

Allergic asthma can cause airway structural remodeling, involving the accumulation of extracellular matrix and thickening of smooth muscle. Tumor necrosis factor (TNF) family ligand LIGHT (TNFSF14) is a cytokine that binds herpesvirus entry mediator (HVEM)/TNFRSF14 and lymphotoxin β receptor (LTβR). LIGHT induces asthmatic cytokine IL-13 and fibrogenic cytokine transforming growth factor-β release from allergic asthma-related eosinophils expressing HVEM and alveolar macrophages expressing LTβR, respectively, thereby playing crucial roles in asthmatic airway remodeling. In this study, we investigated the effects of LIGHT on the coculture of human basophils/eosinophils and bronchial epithelial BEAS-2B cells. The expression of adhesion molecules, cytokines/chemokines, and matrix metalloproteinases (MMP) was measured by flow cytometry, multiplex, assay or ELISA. Results showed that LIGHT could significantly promote intercellular adhesion, cell surface expression of intercellular adhesion molecule-1, release of airway remodeling-related IL-6, CXCL8, and MMP-9 from BEAS-2B cells upon interaction with basophils/eosinophils, probably via the intercellular interaction, cell surface receptors HVEM and LTβR on BEAS-2B cells, and extracellular signal-regulated kinase, p38 mitogen activated protein kinase, and NF-κB signaling pathways. The above results, therefore, enhance our understanding of the immunopathological roles of LIGHT in allergic asthma and shed light on the potential therapeutic targets for airway remodeling

Effects of karanjin on cell cycle arrest and apoptosis in human A549, HepG2 and HL-60 cancer cells

BACKGROUND: We have investigated the potential anticancer effects of karanjin, a principal furanoflavonol constituent of the Chinese medicine Fordia cauliflora, using cytotoxic assay, cell cycle arrest, and induction of apoptosis in three human cancer cell lines (A549, HepG2 and HL-60 cells). RESULTS: MTT cytotoxic assay showed that karanjin could inhibit the proliferation and viability of all three cancer cells. The induction of cell cycle arrest was observed via a PI (propidium iodide)/RNase Staining Buffer detection kit and analyzed by flow cytometry: karanjin could dose-dependently induce cell cycle arrest at G2/M phase in the three cell lines. Cell apoptosis was assessed by Annexin V-FITC/PI staining: all three cancer cells treated with karanjin exhibited significantly increased apoptotic rates, especially in the percentage of late apoptosis cells. CONCLUSION: Karanjin can induce cancer cell death through cell cycle arrest and enhance apoptosis. This compound may be effective clinically for cancer pharmacotherapy