Research Progress on the Structural Modification of Magnolol and Honokiol and the Biological Activities of Their Derivatives.

Magnolol and Honokiol are the primary active components that have been identified and extracted from Magnolia officinalis, and several investigations have demonstrated that they have significant pharmacological effects. Despite their therapeutic benefits for a wide range of illnesses, research on and the implementation of these compounds have been hindered by their poor water solubility and low bioavailability. Researchers are continually using chemical methods to alter their structures to make them more effective in treating and preventing diseases. Researchers are also continuously developing derivative drugs with high efficacy and few adverse effects. This article summarizes and analyzes derivatives with significant biological activities reported in recent research obtained by structural modification. The modification sites have mainly focused on the phenolic hydroxy groups, benzene rings, and diene bonds. Changes to the allyl bisphenol structure will result in unexpected benefits, including high activity, low toxicity, and good bioavailability. Furthermore, alongside earlier experimental research in our laboratory, the structure-activity relationships of magnolol and honokiol were preliminarily summarized, providing experimental evidence for improving their development and utilization.

Predictive factors of persistent infantile atopic dermatitis up to 6 years old in Taiwan: a prospective birth cohort study.

BACKGROUND: Atopic dermatitis affects 15-30% of children worldwide. Onset of disease usually occurs within the first year of life, over half of which regress by 6 years of age. The aim of this study was to investigate the risk factors related to the persistence of infantile atopic dermatitis. METHODS: In this birth cohort study, patients were enrolled prenatally and followed until 6 years of age; 246 patients had infantile atopic dermatitis at 6 months of age. Family history, maternal and paternal total and specific Immunoglobulin E (IgE) levels, and cord blood IgE were recorded. Clinical examination, questionnaire survey, and blood samples for total and specific IgE of the children were collected at each follow-up visit. RESULTS: Of the 246 patients with infantile atopic dermatitis at 6 months of age, 48 patients had persisted atopic dermatitis at 6 years of age (19.5%). Risk factors associated with persistent infantile atopic dermatitis included egg white sensitization (odds ratio: 3.801, P = 0.020), and atopic dermatitis involving two or more areas at 6 months old (odds ratio: 2.921, P = 0.018) after multivariate analysis with logistic regression. Patients with persistent infantile atopic dermatitis had a higher risk of asthma before 6 years old (39.6% vs 24.2%, P = 0.032). CONCLUSION: Egg white sensitization and the initial involvement of two or more areas at 6 months of age were associated with the persistent infantile atopic dermatitis. Patients with persistent infantile atopic dermatitis are more likely to develop asthma by 6 years of age.

Expression of plzfa in embryo and adult of medaka Oryzias latipes.

In this study, a homologous gene named plzfa was identified and characterized in medaka Oryzias latipes. Oryzias latipes plzfa was detected in all the tissues including brain, gill, muscle, liver, intestine, kidney, spleen, testis and ovary using reverse transcriptase (RT)-PCR. plzfa was detected in the oocytes of the ovary and in the spermatogonia and somitic cells of the testis by in situ hybridization. plzfa had a maternal origin with continuous and dynamic expression during embryonic development. plzfa was observed in the brain, neural rod and sensor organs including the eyes, ears and nose during embryogenesis. plzfa was also detected in the neural crest, somite, pectoral fin, intestine and skin. These results indicate that plzfa is a pleiotropic gene that may play major roles in various tissues.

Th17- and Treg-related cytokine and mRNA expression are associated with acute and resolving Kawasaki disease.

BACKGROUND: Kawasaki disease is a vasculitis most commonly afflicting children <5 years of age. Many autoimmune diseases are associated with up-regulation of T helper (Th) 17 cells, and down-regulation Treg cells. Few studies have examined the Th17/Treg expression in Kawasaki disease. METHODS: Blood samples were obtained from 186 children with Kawasaki disease at 24 h before IVIG therapy, followed by 3 days and 21 days after IVIG therapy. Thirty children with an acute febrile infectious disease and 30 healthy children were obtained as control. Plasma levels of Th17- and Treg-related cytokines including IL-6, IL-17A, IL-10, TGF-ß, and mRNA expression levels of RORγt and Foxp3 were tested. RESULTS: Patients with Kawasaki disease had higher levels of plasma IL-17A (25.35 ± 3.21 vs 7.78 ± 1.78 pg/ml, P < 0.001) and IL-6 (152.29 ± 21.94 vs 38.63 ± 12.40 pg/ml, P < 0.001) when compared to the febrile control group. IVIG resulted in a reduction in IL-6 and IL-17A at both 3 and 21 days after IVIG therapy. FoxP3 levels increased significantly 3 days after IVIG therapy (2.28 ± 0.34 vs 0.88 ± 0.14, P < 0.001). IVIG resistance was associated with higher levels of IL-10 and IL-17A. CONCLUSION: Kawasaki disease was associated with higher IL-17A and IL-6, a cytokine profile similar to other autoimmune diseases. IVIG therapy resulted in increased expression of Treg-related FoxP3. IVIG resistance was associated with higher levels of IL-10 and IL-17A. Our findings provide further evidence that Kawasaki disease is an autoimmune-like disease.

Anti-platelet and anti-thrombosis characteristics of Z4A5, a novel selective platelet glycoprotein IIb/IIIa inhibitor, compared with eptifibatide under long-term infusion.

Platelet Glycoprotein IIb/IIIa inhibitors are approved for the treatment of acute coronary syndromes and percutaneous coronary interventions due to their effects on the final common pathway of platelet aggregation. Z4A5 is a new hexapeptide IIb/IIIa inhibitor with antiplatelet and antithrombotic effects. This study was performed to assess the characteristics of Z4A5 compared with another IIb/IIIa inhibitor eptifibatide. Light-transmission aggregometry was used to measure platelet aggregation to assess the antiplatelet efficacy of Z4A5 in vitro and ex vivo in beagles. The time course of platelet inhibition and bleeding time prolongation during i.v. bolus plus infusion and after infusion of the Z4A5 were evaluated in beagles following two 2 x 2 Latin square designs. We also compared the antithrombotic activity of Z4A5 with eptifibatide in arterial thrombosis and arteriovenous shunt thrombosis model in beagles. Our data showed that Z4A5 completely inhibited adenosine diphosphate (ADP)-, thrombin- and arachidonic acid-induced in vitro platelet aggregation with values of IC50 of 260 nM, 128.6 and 56.4 n respectively. Z4A5 also markedly and stably prevented ADP-induced ex vivo platelet aggregation and prolonged the bleeding time throughout the 8-hour infusion. Both platelet function and bleeding time returned to normal sooner after cessation of Z4A5 infusion than after eptifibatide. Z4A5 inhibited thrombosis and had the same potent antithrombotic activity as eptifibatide. In conclusion, Z4A5 has the same potent antiplatelet effect and antithrombotic activity with the advantage of a faster on and off time compared to eptifibatide.

Assessment of cell binding to hyaluronic acid in a solid-phase assay.

Adhesion to hyaluronate by tumor cells has been shown to correlate with disease progression in various types of neoplasms. In order to study cell binding to hyaluronate, a novel assay was developed with hyaluronate covalently tethered to polystyrene plates in 96-well format. Hyaluronic acid is covalently linked to amine groups on the surface of these plates by 1-ethyl-3(3-dimethylaminopropyl) carbodiimide. The amide linkage is stable to repeated washings, and cell binding to this derivatized surface is highly reproducible. Use of plates coated with hyaluronate by this new method provides an ideal in vitro model system for assaying cell binding.

HIV acquires functional adhesion receptors from host cells.

CD4 is known to serve as the principal cellular receptor for HIV. However, several observations suggest that other molecules may be involved in infection of cells by HIV. Cell adhesion molecules and their ligands expressed on HIV-susceptible cells have been implicated in the biology of HIV in a number of studies. We have recently reported that HIV and SIV acquire cell adhesion molecules from host cells. We now report that a specific cell adhesion molecule, CD44, that is acquired by HIV retains its biological activity when expressed on the virus. We tested CEMx174 cells, which are CD4-positive and HIV-susceptible for phorbol ester-inducible binding to hyaluronic acid through CD44. Phorbol ester-stimulated but not unstimulated CEMx174 cells bound hyaluronic acid. Likewise, HIV from stimulated cells but not from unstimulated cells bound hyaluronic acid through acquired CD44 molecules. This is the first demonstration that adhesion molecules acquired by HIV are functional and the results imply that HIV may have the capacity to bind to any cell or substrate that its host cell binds to. The demonstration of functional adhesion receptors on HIV has important implications with respect to the tropism, infectivity, and dissemination of HIV.

HIV-induced loss of CD44 expression in monocytic cell lines.

We have found that HIV-1 infection of monocytic cell lines results in a new adhesion phenotype. Whereas uninfected cells grow as single cell suspensions, HIV-infected cells grow as large aggregates. When the expression of adhesion molecules was investigated, CD44 was almost completely depleted from the surface of HIV-infected cells. Immunoprecipitation with mAb confirmed the loss of CD44 from the surface of infected cells. In addition, loss of surface CD44 was not due to formation of internal complexes or release into the culture supernatant. Soluble CD44 was not detected in culture supernatant from HIV-infected cells. Northern blot analysis showed an altered RNA pattern in HIV-infected cells. The high molecular mass CD44 RNA (7.0 kb) was lost from infected cells, and the low molecular mass CD44 RNA (1.2 kb) remained. We have previously shown that anti-CD44 mAb induces homotypic adhesion in CD44+ cell lines. In this report, we show that homotypic adhesion of the HIV-infected cells occurs through a different mechanism than anti-CD44 mAb-induced aggregation. The homotypic adhesion in infected cells was CD18-mediated, but anti-CD44 mAb-induced homotypic adhesion in uninfected cells was CD18-independent. The change in adhesion phenotype and the loss of CD44 from the surface of HIV-1-infected monocytic cells are discussed in terms of their potential implications in cell-to-cell transmission of HIV.