Design of Trehalose-Based Amide/Sulfonamide C-type Lectin Receptor Signaling Compounds

Mincle agonists have been shown to induce inflammatory cytokine production, such as tumor necrosis factor-alpha (TNF) and promote the development of a Th1/Th17 immune response that might be crucial to development of effective vaccination against pathogens such as Mycobacterium tuberculosis. As an expansion of our previous work, a library of 6,6′-amide and sulfonamide α,α-d -trehalose compounds with various substituents on the aromatic ring was synthesized efficiently in good to excellent yields. These compounds were evaluated for their ability to activate the human C-type lectin receptor Mincle by the induction of cytokines from human peripheral blood mononuclear cells. A preliminary structure–activity relationship (SAR) of these novel trehalose diamides and sulfonamides revealed that aryl amide-linked trehalose compounds demonstrated improved activity and relatively high potency cytokine production compared to the Mincle ligand trehalose dibehenate adjuvant (TDB) and the natural ligand trehalose dimycolate (TDM) inducing dose-dependent and human-Mincle-specific stimulation in a HEK reporter cell line.     

5-Benzylidene-4-Oxazolidinones Are Synergistic with Antibiotics for the Treatment of Staphylococcus aureus Biofilms

The failure of frontline antibiotics in the clinic is one of the most serious threats to human health and requires a multitude of novel therapeutics and innovative approaches to treatment so as to curtail the growing crisis. In addition to traditional resistance mechanisms resulting in the lack of efficacy of many antibiotics, most chronic and recurring infections are further made tolerant to antibiotic action by the presence of biofilms. Herein, we report an expanded set of 5-benzylidene-4-oxazolidinones that are able to inhibit the formation of Staphylococcus aureus biofilms, disperse preformed biofilms, and, in combination with common antibiotics, are able to significantly reduce the bacterial load in a robust collagen-matrix model of biofilm infection.     

九种助剂对草甘膦的增效作用比较

草甘膦异丙胺盐药液中分别加入九种助剂后对空心莲子草喷多处理，测定植株鲜重及再生植株鲜重，并测定药液的表面张力。结果表明，药液中助剂UC—12、TI—800、JFC、Tween20的浓度达到1000—5000mg/L时鲜重抑制率比CK提高了6—20个百分点。加入UC—12、JFC对根茎抑制作用最为明显，复发率降低了约12个百分点。九种助剂降低药液表面张力的效能从高到低顺序为：农乳500＞904＞APG＞JFC＞TL800＞UC-12＞Tween20＞961＞SD。上述试验结果表明，助剂UC-12、TI—800、JFC、Tween20对草甘膦的增效作用较为显著，助剂增效作用大小与降低表面张力的效能无密切相关性。     

赤霉素A_(4+7)水剂的稳定性研究

当温度超过50℃时,赤霉素A4+7(GA4+7)水溶液,容易分解而失去活性。研究表明:加入适量的农药助剂M,可以明显提高GA4+7水剂的稳定性,使其热贮分解率在5%以下,达到农药制剂热贮稳定性的要求。     

Immune and Anticancer Responses Elicited by Fully Synthetic Aberrantly Glycosylated MUC1 Tripartite Vaccines Modified by a TLR2 or TLR9 Agonist

The mucin MUC1 is overexpressed and aberrantly glycosylated by many epithelial cancer cells manifested by truncated O‐linked saccharides. Although tumor‐associated MUC1 has generated considerable attention because of its potential for the development of a therapeutic cancer vaccine, it has been difficult to design constructs that consistently induce cytotoxic T‐lymphocytes (CTLs) and ADCC‐mediating antibodies specific for the tumor form of MUC1. We have designed, chemically synthesized, and immunologically examined vaccine candidates each composed of a glycopeptide derived from MUC1, a promiscuous T_helper peptide, and a TLR2 (Pam₃CysSK₄) or TLR9 (CpG‐ODN 1826) agonist. It was found that the Pam₃CysSK₄‐containing compound elicits more potent antigenic and cellular immune responses, resulting in a therapeutic effect in a mouse model of mammary cancer. It is thus shown, for the first time, that the nature of an inbuilt adjuvant of a tripartite vaccine can significantly impact the quality of immune responses elicited against a tumor‐associated glycopeptide. The unique adjuvant properties of Pam₃CysSK₄, which can reduce the suppressive function of regulatory T cells and enhance the cytotoxicity of tumor‐specific CTLs, are likely responsible for the superior properties of the vaccine candidate 1 .     

Ultrasmall Graphene Oxide Supported Gold Nanoparticles as Adjuvants Improve Humoral and Cellular Immunity in Mice

Adjuvants play an important role in vaccines. Alum and MF59 are two dominant kinds of adjuvants used in humans. Both of them, however, have limited capacity to generate the cellular immune response required for vaccines against cancers and viral diseases. It is desirable to develop new and efficient adjuvants with the aim of improving the cellular immune response against the antigen. Here, the feasibility and efficiency of ultrasmall graphene oxide supported gold nanoparticles (usGO‐Au) as a new immune adjuvant to improve immune responses are explored. usGO‐Au is obtained from reduction of chloroauric acid using usGO and then decorated with ovalbumin (OVA, a model antigen) through physical adsorption to construct usGO‐Au@OVA. As the results show, the as‐synthesized usGO‐Au@OVA can efficiently stimulate RAW264.7 cells to secrete tumor necrosis factor‐α (TNF‐α), a mediator for cellular immune response. In vivo studies demonstrate that usGO‐Au@OVA can also promote robust OVA specific antibody response, CD8⁺ T cells proliferation, and different cytokines secretion. The results indicate that using usGO‐Au as an adjuvant can stimulate potent humoral and cellular immune responses against antigens, which may promote better understanding of cellular immune response and facilitate potential applications for cancer and viral vaccines.     

Surface application of calcium‐containing gels to improve quality of late maturing peach cultivars

BACKGROUND: A strategy to supply Ca directly to fruits as a tool for improving peach quality has been devised and tested under field conditions. Since peaches in the area of study (Calanda, Spain) are routinely bagged shortly after thinning, a method based on the application of Ca gels to the fruit surface was introduced. The effect of surface treatments was assessed in terms of quality, nutrient balance and surface deposition. RESULTS: Application of Ca‐containing formulations increased mesocarp and exocarp Ca concentrations, providing evidence for the penetration of Ca through the peach skin. Surface Ca treatments had a particular mode of deposition and in some instances improved the shelf life of fruits without affecting their quality. CONCLUSION: Surface treatment with Ca‐containing gels appears to be a viable approach to increase fruit Ca, quality and storability of bagged peach cultivars and should be optimised in future studies. Copyright © 2009 Society of Chemical Industry     

Nonglycosidic Agonists of Invariant NKT Cells for Use as Vaccine Adjuvants

Based on the crystal structures of human α‐GalCer–CD1d and iNKT–α‐GalCer–CD1d complexes, nonglycosidic analogues of α‐GalCer were synthesized. They activate iNKT cells resulting in dendritic cell maturation and the priming of antigen‐specific T and B cells. Therefore, they are attractive adjuvants in vaccination strategies for cancer and infectious diseases.

     

Subunit-based mucosal vaccine delivery systems for pulmonary delivery - Are they feasible?

Pulmonary infections are the most common cause of death globally. However, the development of mucosal vaccines that provide protective immunity against respiratory pathogens are limited. In contrast to needle-based vaccines, efficient vaccines that are delivered via noninvasive mucosal routes (such as via the lungs and nasal passage) produce both antigen-specific local mucosal IgA and systemic IgG protective antibodies. One major challenge in the development of pulmonary vaccines using subunit antigens however, is the production of optimal immune responses. Subunit vaccines therefore rely upon use of adjuvants to potentiate immune responses. While the lack of suitable mucosal adjuvants has hindered progress in the development of efficient pulmonary vaccines, particle-based systems can provide an alternative approach for the safe and efficient delivery of subunit vaccines. In particular, the rational engineering of particulate vaccines with optimal physicochemical characteristics can produce long-term protective immunity. These protect antigens against enzymatic degradation, target antigen presenting cells and initiate optimal humoral and cellular immunity. This review will discuss our current understanding of pulmonary immunology and developments in fabricating particle characteristics that may evoke potent and durable pulmonary immunity.