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To address a key challenge of conjugated polymers in biomedical applications having poor antifouling properties that eventually leads to the failure and reduced lifetime of bioelectronics in the body, herein we describe the design, synthesis, and evaluation of our newly designed multifunctional zwitterionic liquid crystalline polymer PCBTh-C8C10 , which is facilely synthesized using oxidative polymerization. A conjugated polythiophene backbone, a multifunctional zwitterionic side chain, and a mesogenic unit are integrated into one segment. By DSC and POM characterization, we verify that the introduction of 3,5-bis(2-octyl-1-dodecyloxy)benzene as a mesogenic unit into the polythiophene backbone allows the formation of the liquid crystalline mesophase of the resulting polymer. We also demonstrate that the PCBTh-C8C10 coated surface exhibits good conductivity, stability, hydrophilicity, and remarkable antibiofouling properties against protein adsorption, cell growth, and bacteria attachment. This new zwitterionic liquid crystalline polymer having good antibiofouling features will be widely recognized as a promising biomaterial that is applicable in implantable organic bioelectronics via inhibiting the foreign body response. A deep understanding of structure–property relationships of zwitterionic conjugated polymers has also been provided in this study. 

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology. 

Human gingival fibroblasts (HGFs) recognize microbe-associated molecular patterns (MAMPs) and respond with inflammatory proteins. Simultaneous impacts of bacterial cyclic di-guanosine monophosphate (c-di-GMP), cyclic di-adenosine monophosphate (c-di-AMP), and lipopolysaccharide (LPS) on gingival keratinocytes have been previously demonstrated, but the effects of these MAMPs on other periodontal cell types, such as gingival fibroblasts, remain to be clarified. The present aim was to examine the independent and combined effects of these cyclic dinucleotides and LPS on interleukin (IL) and matrix metalloproteinase (MMP) response of HGFs. The cells were incubated with c-di-GMP and c-di-AMP, either in the presence or absence of Porphyromonas gingivalis LPS, for 2 h and 24 h. The levels of IL-8, -10, and -34, and MMP-1, -2, and -3 secreted were measured by the Luminex technique. LPS alone or together with cyclic dinucleotides elevated IL-8 levels. IL-10 levels were significantly increased in the presence of c-di-GMP and LPS after 2 h but disappeared after 24 h of incubation. Concurrent treatment of c-di-AMP and LPS elevated MMP-1 levels, whereas c-di-GMP with LPS suppressed MMP-2 levels but increased MMP-3 levels. To conclude, we produce evidence that cyclic dinucleotides interact with LPS-mediated early response of gingival fibroblasts, while late cellular response is mainly regulated by LPS. 

Cyclic guanosine monophosphate‐adenosine monophosphate and other bacterial‐derived cyclic di‐guanosine monophosphate or cyclic di‐adenosine monophosphate trigger innate immune responses through binding to stimulator of interferon genes (STING). Thus in chronic infection, such as in periodontitis, immune cells can be exposed to bacterial DNA and/or cyclic dinucleotides, potentially activating STING to cause inflammation. Thus far the cyclic GMP‐AMP synthase‐STING‐ TANK‐binding kinase 1 pathway has been well characterized but a global perspective of how the presence or lack of STING affect the proteome is lacking. The aim of this study is to identify macrophage proteins that are affected by STING.

Proteins are extracted from a macrophage cell line harboring STING (RAW‐Blue ISG) as well as a STING knockout (STING KO) cell line (RAW‐Lucia ISG‐KO‐STING) and global proteomics analyses are performed.

Proteins related to kinase and phosphatase signaling, spliceosome, terpenoid backbone biosynthesis, glycosylation, ubiquitination, and phagocytosis are affected by STING knock out.

STING pathway in macrophages is related to the regulation of several proteins that are known as potent biomarkers of various cancers and autoimmune diseases. Moreover, the relation between STING and phagocytosis is demonstrated for the first time. Further validation studies will help identify molecules and pathways that may function as diagnostic or therapeutic targets.