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1. Superparamagnetic nanoparticles for the treatment of periodontal disease

   https://doi.org/10.1117/12.2654656  

   Fritz, Shayden; Armijo, Leisha M.; Simpson, Kayla; Lopez, Kimberly; Osinski, Marek; Bandara, Nihal; Smyth, Hugh D.; Sheng, Jian; Xu, Wei (March 2023, Colloidal Nanoparticles for Biomedical Applications XVIII)

   Osiński, Marek; Kanaras, Antonios G. (Ed.)

   Periodontal diseases are prevalent worldwide and are linked to numerous other health conditions due to dysbiosis and chronic inflammatory state. Most periodontal diseases are caused by pathogenic bacteria that colonize dental tissues in the form of biofilm. Eradication of bacterial biofilms can be difficult to achieve due to the complex architecture of the teeth and gums which complicates the removal. Orthodontic wires and dental devices introduce additional hurdles to the adequate removal of biofilms by traditional methods since mechanical disruption via direct contact with toothbrush bristles, floss, and abrasive toothpaste is limited. Magnetically activated nanoparticles (NPs), specifically iron oxide nanoparticles (IONPs) that can be functionalized as antimicrobial particles and remotely controlled by magnetic fields, are of interest for oral biofilm eradication. We present data in multi-species bacterial cultures, established biofilms, human gingival keratinocytes, and human gingival fibroblast cells alone and in the presence of multispecies biofilm co-cultures to determine the safest, most efficacious IONP size ranges and treatment concentrations of active magnetic NPs for removal of dental biofilms. We report enhanced efficacy for IONPs coated with alginate vs. dextran, and small sizes (~8 nm vs. >20 nm in size) appear to exhibit enhanced antimicrobial efficacy. Human gingival keratinocyte (TIGK) cells in co-culture with treated and untreated multispecies biofilms in an in-vitro periodontitis model also exhibited a trend of reduced inflammatory markers in wells with IONP-treated biofilms. 

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2. The Vibrio type VI secretion system induces intestinal macrophage redistribution and enhanced intestinal motility

   https://doi.org/10.1128/mbio.02419-24  

   Ngo, Julia S; Amitabh, Piyush; Sokoloff, Jonah G; Trinh, Calvin; Wiles, Travis J; Guillemin, Karen; Parthasarathy, Raghuveer (January 2025, mBio)

   Graf, Joerg (Ed.)

   Intestinal microbes, whether resident or transient, influence the physiology of their hosts, altering both the chemical and the physical characteristics of the gut. An example of the latter is the human pathogenVibrio cholerae’sability to induce strong mechanical contractions, discovered in zebrafish. The underlying mechanism has remained unknown, but the phenomenon requires the actin crosslinking domain (ACD) ofVibrio’s type VI secretion system (T6SS), a multicomponent protein syringe that pierces adjacent cells and delivers toxins. By using a zebrafish-nativeVibrioand imaging-based assays of host intestinal mechanics and immune responses, we find evidence that macrophages mediate the connection between the T6SS ACD and intestinal activity. Inoculation withVibriogives rise to strong, ACD-dependent, gut contractions whose magnitude resembles those resulting from genetic depletion of macrophages.Vibrioalso induces tissue damage and macrophage activation, both ACD-dependent, recruiting macrophages to the site of tissue damage and away from their unperturbed positions near enteric neurons that line the midgut and regulate intestinal motility. Given known crosstalk between macrophages and enteric neurons, our observations suggest that macrophage redistribution forms a key link betweenVibrioactivity and intestinal motility. In addition to illuminating host-directed actions of the widespread T6SS protein apparatus, our findings highlight how localized bacteria-induced injury can reshape neuro-immune cellular dynamics to impact whole-organ physiology. IMPORTANCEGut microbes, whether beneficial, harmful, or neutral, can have dramatic effects on host activities. The human pathogenVibrio choleraecan induce strong intestinal contractions, though how this is achieved has remained a mystery. Using a zebrafish-nativeVibrioand live imaging of larval fish, we find evidence that immune cells mediate the connection between bacteria and host mechanics. A piece ofVibrio’s type VI secretion system, a syringe-like apparatus that stabs cellular targets, induces localized tissue damage, activating macrophages and drawing them from their normal residence near neurons, whose stimulation of gut contractions they dampen, to the damage site. Our observations reveal a mechanism in which cellular rearrangements, rather than bespoke biochemical signaling, drives a dynamic neuro-immune response to bacterial activity. 

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3. Activation of Gingival Fibroblasts by Bacterial Cyclic Dinucleotides and Lipopolysaccharide

   https://doi.org/10.3390/pathogens9100792  

   Elmanfi, Samira; Sintim, Herman O.; Zhou, Jie; Gürsoy, Mervi; Könönen, Eija; Gürsoy, Ulvi K. (October 2020, Pathogens)

   null (Ed.)

   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. 

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4. Beta-Amyloid Instigates Dysfunction of Mitochondria in Cardiac Cells

   https://doi.org/10.3390/cells11030373  

   Jang, Sehwan; Chapa-Dubocq, Xavier R.; Parodi-Rullán, Rebecca M.; Fossati, Silvia; Javadov, Sabzali (February 2022, Cells)

   Alzheimer’s disease (AD) includes the formation of extracellular deposits comprising aggregated β-amyloid (Aβ) fibers associated with oxidative stress, inflammation, mitochondrial abnormalities, and neuronal loss. There is an associative link between AD and cardiac diseases; however, the mechanisms underlying the potential role of AD, particularly Aβ in cardiac cells, remain unknown. Here, we investigated the role of mitochondria in mediating the effects of Aβ1-40 and Aβ1-42 in cultured cardiomyocytes and primary coronary endothelial cells. Our results demonstrated that Aβ1-40 and Aβ1-42 are differently accumulated in cardiomyocytes and coronary endothelial cells. Aβ1-42 had more adverse effects than Aβ1-40 on cell viability and mitochondrial function in both types of cells. Mitochondrial and cellular ROS were significantly increased, whereas mitochondrial membrane potential and calcium retention capacity decreased in both types of cells in response to Aβ1-42. Mitochondrial dysfunction induced by Aβ was associated with apoptosis of the cells. The effects of Aβ1-42 on mitochondria and cell death were more evident in coronary endothelial cells. In addition, Aβ1-40 and Aβ1-42 significantly increased Ca2+ -induced swelling in mitochondria isolated from the intact rat hearts. In conclusion, this study demonstrates the toxic effects of Aβ on cell survival and mitochondria function in cardiac cells. 

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5. Guanidinium-Functionalized Photodynamic Antibacterial Oligo(Thiophene)s

   https://doi.org/10.1557/adv.2019.359  

   Zhou, Zhe; Ergene, Cansu; Palermo, Edmund F. (September 2019, MRS Advances)

   ABSTRACT We synthesized precision oligomers of thiophene with cationic and hydrophobic side chains to mimic the charge, hydrophobicity, and molecular size of antibacterial host defense peptides (HDPs). In this study, the source of cationic charge was a guanidinium salt moiety intended to reflect the structure of arginine-rich HDPs. Due to the pi-conjugated oligo(thiophene) backbone structure, these compounds absorb visible light in aqueous solution and react with dissolved oxygen to produce highly biocidal reactive oxygen species (ROS). Thus, the compounds exert bactericidal activity in the dark with dramatically enhanced potency upon visible light illumination. We find that guanylation of primary amine groups enhanced the activity of the oligomers in the dark but also mitigated their light-induced activity enhancement. In addition, we also quantified their toxicity to mammalian cell membranes using a hemolysis assay with red blood cells, in the light and dark conditions. 

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