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Osteoporosis is a prevalent bone condition with adverse effects observed in patients undergoing long-term glucocorticoid therapy, resulting in bone demineralization and tissue loss. There has been limited studies on the global response to dexamethasone in terms of comparing its expression profile to other common glucocorticoids during osteogenic differentiation. This study focused on the downregulated gene expression profile of glucocorticoid compounds; dexamethasone, budesonide, and fluticasone propionate, during osteogenic differentiation to elucidate the related target genes and pathways associated with the anti-osteoporotic potential of telomerase-immortalized human bone marrow-derived mesenchymal stem cells using a bioinformatics approach. Based on gene expression microarrays experiments and bioinformatics analysis, several key genes involved in the regulation of osteogenic differentiation and osteoporosis development in mesenchymal stem cells that were targeted by these specific glucocorticoids were determined. Network analysis using GeneCards, OMIM, and CTD databases were performed and osteoporosis-related genes were identified. LIMMA and moderated Welch test R packages were performed to determine significant downregulated differentially expressed genes for each glucocorticoid treatment. A total of 479 (dexamethasone), 84 (budesonide), and 889 (fluticasone propionate) differentially expressed genes were identified for each glucocorticoid, of which 35 common genes overlapped. Enrichment pathway analysis was conducted using Metascape, and protein-protein interaction networks were constructed using the STRING database and Cytoscape software to determine potential target genes involved with osteoporosis. Enrichment pathway analysis revealed genes involved in 3 Reactome pathways namely cytokine signaling in immune system, immune system and the interferon alpha/beta signaling pathways and identified 10 hub genes based on the PPI network to determine potential target pathways associated with osteoporosis. These findings provide preliminary insights into the relationship between the key target genes of dexamethasone, budesonide, and fluticasone propionate, and the pathways associated with regulated osteoporosis metabolism during osteogenic differentiation.

Background: Saudi Arabia has an overall smoking rate of 15.9%. The link between smoking and periodontal disease has been studied extensively. It is possible for human gingival fibroblasts to accumulate nicotine intracellularly over a period of four hours. Additionally, unmetabolized nicotine is released into the environment. Tobacco presence can impair tissue inflammation, wound healing, and organ development. To counterbalance tobacco toxins, vitamin C has been added to a variety of products. Aim: This study aims to analyze the RNA expression of antioxidant, anti-inflammatory, and wound healing proteins in human gingival fibroblasts from smokers and nonsmokers using polymerase chain reaction. Materials and Methods: hGFs were extracted from clinically healthy periodontium sites of adult male subjects. Both heavy cigarette smokers and never-smokers participated as subjects. Cells were cultured and subcultured in supplemented growth medium. Vitamin C was inducted in the medium at the experimental 6th passage. RNA expression analysis (qRT-PCR) was performed to analyze adhesion, proliferation, and extracellular matrix expression. Results: The results revealed marked expression of a wound healing gene (VEGF-A) in never-smokers (p value = 0.016). GPX3 and SOD3 represent antioxidants that are highly expressed in treated never-smoker cells. SOD2 significantly increased (p value = 0.016) in smokers after vitamin C exposure. The anti-inflammatory markers IL-6 and IL-8 were lower among smokers than among nonsmokers (p

Background: Porphyromonas gingivalis (P. gingivalis) is viewed as a keystone microorganism in the pathogenesis of periodontal and peri-implant diseases. Hyaluronic acid (HA) is believed to exert antimicrobial activity. The aim of this study is to assess the in-vitro growth and biofilm formation of P. gingivalis under HA and compare the effect of HA to that of azithromycin (AZM) and chlorhexidine (CHX). Materials and methods: In each material, the minimum inhibitory concentration (MIC), 50% MIC, 25% MIC, and 12.5% MIC were tested. The growth of P. gingivalis was evaluated by absorbance spectrophotometry after 48 h. A biofilm inhibition assay was performed on a 72-hour culture by washing planktonic bacterial cells, fixing and staining adherent cells, and measuring the variation in stain concentrations relative to the untreated control using absorbance spectrophotometry. Results: The results show that the overall growth of P. gingivalis after 48 h was 0.048 ± 0.030, 0.008 ± 0.013, and 0.073 ± 0.071 under HA, AZM, and CHX, respectively, while the untreated control reached 0.236 ± 0.039. HA was also able to significantly reduce the biofilm formation of P. gingivalis by 64.30 % ± 22.39, while AZM and CHX reduced biofilm formation by 91.16 %±12.58 and 88.35 %±17.11, respectively. Conclusions: High molecular-weight HA significantly inhibited the growth of P. gingivalis. The overall effect of HA on the growth of P. gingivalis was similar to that of CHX but less than that of AZM. HA was also able to significantly reduce the biofilm formation of P. gingivalis. However, the ability of HA to prevent the biofilm formation of P. gingivalis was generally less than that of both AZM and CHX.

The LuxS quorum sensing system is considered as the main system that most of the oral bacteria use to communicate in order to create biofilms. Here we identified 11 of the most important biofilm formers that utilize the LuxS system and presented current and recent information regarding this system. Though different bacterial species are able to communicate thorough the LuxS system, it was also found that cross kingdom communication can occur between bacteria and fungi and bacteria and epithelial cells. Immune response also plays and important role in mitigating the effects of biofilms. Here we identified 6 of the most important molecules that are involved in the immune response to biofilms. These immune molecules maintain the stability in the oral cavity by preventing bacteria from overwhelming the space and simultaneously minimizing the immune response in order not to cause tissue damage. Here we also discuss current research being done in order to maintain the balance in the oral cavity via inhibiting biofilm formation without eradicating oral bacteria in order to prevent the overgrowth of other organisms such as Candida albicans. One approach being used is inhibiting AI-2 intermediates which leads to lack of quorum sensing communication between bacteria through the use of intermediate analogues. Another approach that found success is the utilization of D forms of sugars where D-ribose and D-galactose have been proven to inhibit the LuxS system and subsequently preventing the process of quorum sensing leading to the reduction in biofilm formation.

Objectives: Finding alternative methods to overcome antibiotic resistance in the medically important bacterium Pseudomonas aeruginosa has become increasingly vital as antibiotic resistance becomes more difficult to overcome. DNA synthesis inhibition is a strategy that has been used to inhibit cancer cells from proliferating by using pyrimidine analogues. Gateway site-directed mutagenesis is an effective way to create precise knockouts which creates good models to understand the relationship between biochemical pathways and the physiology of the organism. This article demonstrates the effect of pyrimidine synthesis inhibition on the motility virulence and physiology of P. aeruginosa. Methods: Wild type Pseudomonas aeruginosa (PA01) was genetically modified using gateway cloning technology to inhibit the pyrimidine synthesis pathway through the complete knockout of the pyrE gene. The mutant strain was compared to the wild type PA01 in terms of its twitching, swarming and swimming motility forms and biofilm formation abilities. In addition to that, the production of the bacterial surfactant, rhamnolipids, was also measured. Results and conclusions: The inhibition of the pyrimidine synthesis pathway resulted in significant reduction in motility and biofilm capabilities, despite complementing the mutation with uracil to bypass the mutation. Inhibition of the pyrimidine synthesis pathway is thus an effective way to reduce the virulence of Pseudomonas aeruginosa. Even though the bacterium is able to acquire pyrimidines from its surrounding, it was not sufficient enough to overcome the effects of the mutation.

Objective: To evaluate the adhesion of Streptococcus mutans (S. mutans) and related surface properties of ion-releasing resin-based composite (RBC) restorative materials., Methods: Two ion-releasing RBCs, Activa (ACT) and Cention-N (CN), were compared to a conventional RBC (Z350) and a resin-modified glass ionomer cement (Fuji-II-LC). Ten disk-shaped specimens were fabricated for each material (n = 40). After standardized surface polishing procedure, the surface properties of the specimens were evaluated using surface roughness measurements by a profilometer and hydrophobicity using water contact angle measurements. To assess bacterial adhesion, the number of S. mutans bacteria was calculated from colony-forming units (CFU). Confocal laser scanning microscope analysis was done for qualitative & quantitative assessment. The data were analyzed using One-way ANOVA followed by Tukey's post-hoc test to compare the mean values of surface roughness, water contact angle and CFU values. To compare the mean dead cell percentage Kruskal-Wallis rank test and Conover test were used. A p-value of ≤ 0.05 was used to report the statistical significance., Results: Z350 and ACT had the smoothest surfaces, followed by CN, and the roughest surface was seen in FUJI-II-LC. The lowest water contact angles were seen in CN, and Z350, and the highest were in ACT. S. mutans counts were the highest in ACT and the lowest in Z350 and CN. CN and Fuji-II-LC registered the highest percentage of dead bacterial cells, while the lowest were in ACT., Significance: Surface properties did not significantly influence bacterial adhesion. More S. mutans bacteria accumulated on ACT than on the nanofilled composite and on CN. CN had antibacterial effects against Streptococcus mutans biofilms., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest, and there has been no significant financial interest in any company or any products mentioned in this manuscript that could have influenced the outcome., (Copyright © 2023 Elsevier Ltd. All rights reserved.)