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Dental plaque is the main cause leading to the dental caries and periodontal diseases. The main purpose of this study was to test the efficacy of oral spray containing the antimicrobial peptide P-113 on the reduction of oral bacteria number and dental plaque formation in a randomized clinical assessment. This study was divided into two parts. In Part A, we investigated the user experiences with the P-113 containing oral spray. In part B, 14 subjects in the experimental group used the P-113-containing oral spray, while 14 subjects in the control group used a placebo without the P-113 in a 4-week clinical trial. Participants were asked to use the P-113-containing oral spray or placebo 3 times per day and 5 times per use. Moreover, 3 check-ups and 2 washouts were carried out to evaluate the DMFT score, dental plaque weight, dental plaque index, and gingival index. In part A, up to 91.8% of the subjects in the experimental group were satisfied with the use of the P-113-containing oral spray. In part B, based on our PacBio SMRT sequencing platform and DADA2 analysis, the numbers of Streptococcus and Porphyromonas in the experimental group were lower than those in the control group. In addition, decreased dental plaque weight, dental plaque index, and gingival index were all observed in the experimental group. The P-113-containing oral spray has the potential to reduce the dental caries and periodontal disease-related bacteria and to control the dental plaque formation. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) governs all aspects of cancer progression and in vitro 3D cell culture platforms are increasingly developed to emulate the interactions between components of the stromal tissues and cancer cells. However, conventional cell culture platforms are inadequate in recapitulating the TME, which has complex compositions and dynamically changing matrix mechanics. In this study, we developed a dynamic gelatin-hyaluronic acid hybrid hydrogel system through integrating modular thiol-norbornene photopolymerization and enzyme-triggered on-demand matrix stiffening. In particular, gelatin was dually modified with norbornene and 4-hydroxyphenylacetic acid to render this bioactive protein photo-crosslinkable (through thiol-norbornene gelation) and responsive to tyrosinase-triggered on-demand stiffening (through HPA dimerization). In addition to the modified gelatin that provides basic cell adhesive motifs and protease cleavable sequences, hyaluronic acid (HA), an essential tumor matrix, was modularly and covalently incorporated into the cell-laden gel network. We systematically characterized macromer modification, gel crosslinking, as well as enzyme-triggered stiffening and degradation. We also evaluated the influence of matrix composition and dynamic stiffening on pancreatic ductal adenocarcinoma (PDAC) cell fate in 3D. We found that either HA-containing matrix or a dynamically stiffened microenvironment inhibited PDAC cell growth. Interestingly, these two factors synergistically induced cell phenotypic changes that resembled cell migration and/or invasion in 3D. Additional mRNA expression array analyses revealed changes unique to the presence of HA, to a stiffened microenvironment, or to the combination of both. Finally, we presented immunostaining and mRNA expression data to demonstrate that these irregular PDAC cell phenotypes were a result of matrix-induced epithelial-mesenchymal transition (EMT). [ABSTRACT FROM AUTHOR]

The complex network of biochemical and biophysical cues in the pancreatic desmoplasia not only presents challenges to the fundamental understanding of tumor progression, but also hinders the development of therapeutic strategies against pancreatic cancer. Residing in the desmoplasia, pancreatic stellate cells (PSCs) are the major stromal cells affecting the growth and metastasis of pancreatic cancer cells by means of paracrine effects and extracellular matrix protein deposition. PSCs remain in a quiescent/dormant state until they are ‘activated’ by various environmental cues. While the mechanisms of PSC activation are increasingly being described in literature, the influence of matrix stiffness on PSC activation is largely unexplored. To test the hypothesis that matrix stiffness affects myofibroblastic activation of PSCs, we have prepared cell-laden hydrogels capable of being dynamically stiffened through an enzymatic reaction. The stiffening of the microenvironment was created by using a peptide linker with additional tyrosine residues, which were susceptible to tyrosinase-mediated crosslinking. Tyrosinase catalyzes the oxidation of tyrosine into dihydroxyphenylalanine (DOPA), DOPA quinone, and finally into DOPA dimer. The formation of DOPA dimer led to additional crosslinks and thus stiffening the cell-laden hydrogel. In addition to systematically studying the various parameters relevant to the enzymatic reaction and hydrogel stiffening, we also designed experiments to probe the influence of dynamic matrix stiffening on cell fate. Protease-sensitive peptides were used to crosslink hydrogels, whereas integrin-binding ligands (e.g., RGD motif) were immobilized in the network to afford cell-matrix interaction. PSC-laden hydrogels were placed in media containing tyrosinase for 6 h to achieve in situ gel stiffening. We found that PSCs encapsulated and cultured in a stiffened matrix expressed higher levels of αSMA and hypoxia-inducible factor 1α (HIF-1α), suggestive of a myofibroblastic phenotype. This hydrogel platform offers a facile means of in situ stiffening of cell-laden matrices and should be valuable for probing cell fate process dictated by dynamic matrix stiffness. Statement of Significance Hydrogels with spatial-temporal controls over crosslinking kinetics (i.e., dynamic hydrogel) are increasingly being developed for studying mechanobiology in 3D. The general principle of designing dynamic hydrogel is to perform cell encapsulation within a hydrogel network that allows for postgelation modification in gel crosslinking density. The enzyme-mediated in situ gel stiffening is innovative because of the specificity and efficiency of enzymatic reaction. Although tyrosinase has been used for hydrogel crosslinking and in situ cell encapsulation, to the best of our knowledge tyrosinase-mediated DOPA formation has not been explored for in situ stiffening of cell-laden hydrogels. Furthermore, the current work provides a gradual matrix stiffening strategy that may more closely mimic the process of tumor development. [ABSTRACT FROM AUTHOR]

New-onset atrial fibrillation (NOAF) is associated with adverse outcomes in patients with coronary artery disease (CAD). Although newer generation drug-eluting stents (NG-DESs) are more beneficial than bare-metal stents (BMSs) in reducing the risk of in-stent restenosis and revascularization, whether NG-DES implantation in patients with stable CAD reduces NOAF risk compared with BMS implantation remains unknown. This population-based cohort study was conducted using data from Taiwan's National Health Insurance Research Database. Propensity score matching was used to select 18,423 pairs of patients with stable CAD receiving NG-DES implantation and BMS implantation with similar baseline characteristics for evaluation. A competing risk model was used to evaluate the risk of NOAF between the NG-DES and BMS groups in which death was considered a competing risk. After adjustment for patients' clinical variables, the use of NG-DESs was associated with a decreased risk of NOAF at 1-year follow-up (adjusted subdistribution hazard ratio [SHR] = 0.79, 95% confidence interval [CI] = 0.68–0.93, P = 0.005) compared with the use of BMSs. Similar results indicated that NG-DESs were beneficial for reducing the risk of NOAF (adjusted SHR = 0.81, 95% CI = 0.67–0.97, P = 0.020) in patients with a CHA 2 DS 2 -VASc score of ≥2. These findings were also consistent with those for patients who received dual antiplatelet therapy for an undefined duration of >1 month following stent implantation. Our findings suggest that NG-DESs might reduce the risk of NOAF in patients with stable CAD. • The strategies to prevent NOAF in patients with stable CAD remain still unclear. • The use of NG-DESs is beneficial to prevent NOAF in patients with stable CAD. • CHA 2 DS 2 -VASc score assists to identify patients who can benefit from NG-DESs implantation. [ABSTRACT FROM AUTHOR]

Abstract: Using a murine hypodermic air pouch infection model designed to mimic the release of bacterial products at physiological levels, 3-hydroxy fatty acid (3-OH FA) and endotoxin unit levels from Burkholderia cenocepacia isolates were assessed. The B. cenocepacia environmental isolates (n=35) survived in the hypodermic air pouch but did not invade across the peritoneal epithelial layer during a 72-h infection. For all 35 strains, when the molar ratio of C14:0 3-OH FA to C16:0 3-OH FA in the air pouch fluid wash samples was between 1.4 and 2.5, the concentrations of C14:0 3-OH FA were correlated with the endotoxin unit levels. However, both surrogate markers exhibited different correlations to the inflammatory response. The linear regression coefficient was 0.4234 for C14:0 3-OH FA concentrations vs. NO productions, 0.223 for endotoxin unit levels vs. NO productions, 0.5008 for C14:0 3-OH FA concentrations vs. TNF-alpha productions and 0.2869 for endotoxin unit levels vs. TNF-alpha productions. Therefore, C14:0 3-OH FA concentrations, rather than endotoxin unit levels, acted as an immunostimulatory indicator for LPS in the B. cenocepacia isolates. [Copyright &y& Elsevier]