Domus Academy

Barrier membranes are essential components of tissue regenerative therapies, acting as physical barriers to protect the healing site. Although collagen-based membranes are widely used, they degrade enzymatically, often triggering inflammation and cytotoxicity arising from residual cross-linking agents. Synthetic polymer-based membranes, such as polydioxanone (PDO), present customizable properties, predictable degradation rates, and induce bone formation more effectively. However, both materials are at risk of exposure to the microbial contamination. To address this, antibiotics have been loaded onto membranes as drug-delivery systems, a strategy that has not yet been explored for PDO membranes. In this study, the oral polymicrobial contamination of PDO-based membranes was evaluated and compared with collagen membranes and aimed to develop an amoxicillin-loaded PDO (AMX-PDO) membrane. For this purpose, PDO membranes with different pore sizes (0.25, 0.50, and 1.00 mm) and two commercially available collagen membranes were evaluated, using in vitro and in situ models, in terms of polymicrobial accumulation. Next, AMX-PDO membranes were developed by glow discharge plasma using Ar and O2 gases and an amoxicillin compound. The findings revealed similar microbial levels for both PDO and collagen-based membranes, but PDO membranes modulated microbial composition with reduced (∼3-5 fold-decrease) levels of specific oral pathogens. The AMX-PDO membrane maintained similar physical and chemical properties to those of untreated membranes, but it significantly reduced polymicrobial accumulation and prevented microbial cells from passing through them. Thus, they acted as more than passive physical barriers only, but rather as biologically active barriers. Therefore, amoxicillin loading on PDO barrier membranes by means of plasma technology seems to be a promising strategy to prevent local infection during regenerative therapy.

L48H37 is a synthetic curcumin analog that has anticancer potentials. Here, we further explored the anticancer effect of L48H37 on oral cancer cells and its mechanistic acts. Cell cycle distribution was assessed using flow cytometric analysis. Apoptosis was elucidated by staining with PI/Annexin V and activation of the caspase cascade. Cellular signaling was explored using apoptotic protein profiling, Western blotting, and specific inhibitors. Our findings showed that L48H37 significantly reduced the cell viability of SCC-9 and HSC-3 cells, resulting in sub-G1 phase accumulation and increased apoptotic cells. Apoptotic protein profiling revealed that L48H37 increased cleaved caspase-3, and downregulated cellular inhibitor of apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP) in SCC-9 cells, and the downregulated cIAP1 and XIAP in both oral cancer cells were also demonstrated by Western blotting. Meanwhile, L48H37 triggered the activation of caspases and mitogen-activated protein kinases (MAPKs). The involvement of c-Jun N-terminal kinase (JNK) and p38 MAPK (p38) in the L48H37-triggered apoptotic cascade in oral cancer cells was also elucidated by specific inhibitors. Collectively, these findings indicate that L48H37 has potent anticancer activity against oral cancer cells, which may be attributed to JNK/p38-mediated caspase activation and the resulting apoptosis. This suggests a potential benefit for L48H37 for the treatment of oral cancer.

<div>Abstract<p><b>Purpose:</b> Multiplexing assay of biomarkers at the point-of-care is an elusive goal for molecular diagnostics.</p><p><b>Experimental Design:</b> Here, we report an electrochemical (EC) sensor for oral cancer detection based on the simultaneous detection of two salivary biomarkers: interleukin (IL)-8 mRNA and IL-8 protein.</p><p><b>Results:</b> Under the multiplexing mode, the limit of detection of salivary IL-8 mRNA reaches to 3.9 fM and 7.4 pg/mL for IL-8 protein in saliva. Multiplex assay of these 2 biomarkers directly from 28 cancer and 28 matched control saliva samples shows significant difference between the two groups. From the receiver operating characteristic analysis, the EC sensor yields around 90% sensitivity and specificity for both IL-8 mRNA and IL-8 protein, which are very close to the data measured by traditional assays (ELISA and PCR) with the same group of saliva. Combined IL-8 mRNA and protein show better AUC compared with single biomarker.</p><p><b>Conclusions:</b> We show, for the first time, concurrently multiplexing detection of salivary mRNA and protein biomarkers using point-of-care EC sensor.</p></div>

The peroxisome proliferator-activated receptor gamma (PPARG) gene encodes a transcription factor involved in the regulation of complex metabolic and inflammatory diseases. We investigated whether single nucleotide polymorphisms (SNPs) and haplotypes of the PPARG gene could contribute with susceptibility to develop periodontitis alone or together with type 2 diabetes mellitus (T2DM). Moreover, we evaluated the gene–phenotype association by assessing the subjects’ biochemical and periodontal parameters, and the expression of PPARG and other immune response–related genes. We examined 345 subjects with a healthy periodontium and without T2DM, 349 subjects with moderate or severe periodontitis but without T2DM, and 202 subjects with moderate or severe periodontitis and T2DM. PPARG SNPs rs12495364, rs1801282, rs1373640, and rs1151999 were investigated. Multiple logistic regressions adjusted for age, sex, and smoking status showed that individuals carrying rs1151999-GG had a 64% lower chance of developing periodontitis together with T2DM. The CCGT haplotype increased the risk of developing periodontitis together with T2DM. The rs1151999-GG and rs12495364-TC were associated with reduced risk of obesity, periodontitis, elevated triglycerides, and elevated glycated hemoglobin, but there was no association with gene expression. Polymorphisms of the PPARG gene were associated with developing periodontitis together with T2DM, and with obesity, lipid, glycemic, and periodontal characteristics.

Purpose: The aim of this study is to investigate if hypochlorous acid (Vashe and Endocyn), Ozone, sodium hypochlorite (0.5% NaOCl), chlorhexidine (0.12% CHX), and MTAD can be used as a disinfectant for endodontic surgery without causing bone tissue toxicity by comparing their cytotoxic effects to saline on osteoblasts in vitro. Methods: Human Fetal Osteoblast Cells (hFOB 1.19, ATCC CRL-11372) were used. The cells viability after 10-minute exposure of Vashe, Endocyn, Ozone, NaOCl (0.5%), CHX (0.12%), MTAD, and saline at concentrations of 10, 30, 60, 90 % volume ratio were measured using CCK8 analysis and the absorbance were measured at 450 nm. Saline was used as a negative control. The morphology changes of the cells after exposure of the testing solutions were compared to the negative media control group using a digital inverted microscope. Results: CCK8 analysis showed 0.5% NaOCl, CHX, MTAD displayed statistically significant cytotoxic effects to osteoblasts as low as 10% concentration compared to saline. Vashe exhibited a concentration dependent cytotoxic effect on osteoblasts. Vashe at 60% and 90% concentration demonstrated statistically significant cytotoxic effects. Endocyn and Ozone at concentrations of 10%, 30%, 60% were not cytotoxic, however, at concentrations of 90%, Endocyn and Ozone produced statistically significant cytotoxic effects. The morphology of cells did not show changes in 10%, 30 % Vashe, 10%, 30% Endocyn, 10%, 30%, 60% Ozone, and all concentration of saline compared to the negative control- media. Morphology of cells were altered after exposure of 10% of 0.5% NaOCl, CHX, and MTAD. Conclusion: This study concluded that 0.5% NaOCl, CHX, and MTAD had a significant cytotoxic effect on osteoblasts at a concentration as low as 10%. They should not be considered as irrigants for endodontic surgery. Vashe, Endocyn less than 30%, and Ozone less than 60% were not cytotoxic to osteoblasts; and they may be considered as irrigants for endodontic surgery, following further research. Saline produced non-cytotoxic effects to osteoblast at all concentrations.

The cause and prevention of recurrent aphthous stomatitis (also called aphthous ulcers or canker sores) are still unknown. This may be due in part to ignorance of the risk factors present in susceptible people. In this systematic review (PROSPERO record #CRD42019122214), we show that most of the risk factors for the disease are single nucleotide genetic polymorphisms in genes related to the functioning of immune system (TLR4, MMP9, E-selectin, IL-1 beta and TNF-alpha). Single nucleotide genetic polymorphisms do not constitute a modifiable risk. This indicates that, at least in part, susceptibility to recurrent aphthous stomatitis is hereditary, and that these factors cannot be modified.

Ionizing radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, and cerebrovascular injuries. We investigated a population of mice that recovered from high-dose radiation to live normal life spans. These "elite-survivors" harbored distinct gut microbiota that developed after radiation and protected against radiation-induced damage and death in both germ-free and conventionally housed recipients. Elevated abundances of members of the bacterial taxa Lachnospiraceae and Enterococcaceae were associated with postradiation restoration of hematopoiesis and gastrointestinal repair. These bacteria were also found to be more abundant in leukemia patients undergoing radiotherapy, who also displayed milder gastrointestinal dysfunction. In our study in mice, metabolomics revealed increased fecal concentrations of microbially derived propionate and tryptophan metabolites in elite-survivors. The administration of these metabolites caused long-term radioprotection, mitigation of hematopoietic and gastrointestinal syndromes, and a reduction in proinflammatory responses.