Adenosine is a nucleoside that is widely distributed in the central nervous system and acts as a central excitatory and inhibitory neurotransmitter in the brain. The protective role of adenosine in different pathological conditions and neurodegenerative diseases is mainly mediated by adenosine receptors. However, its potential role in mitigating the deleterious effects of oxidative stress in Friedreich’s ataxia (FRDA) remains poorly understood. We aimed to investigate the protective effects of adenosine against mitochondrial dysfunction and impaired mitochondrial biogenesis in L-buthionine sulfoximine (BSO)-induced oxidative stress in dermal fibroblasts derived from an FRDA patient. The FRDA fibroblasts were pre-treated with adenosine for 2 h, followed by 12.50 mM BSO to induce oxidative stress. Cells in medium without any treatments or pre-treated with 5 µM idebenone served as the negative and positive controls, respectively. Cell viability, mitochondrial membrane potential (MMP), aconitase activity, adenosine triphosphate (ATP) level, mitochondrial biogenesis, and associated gene expressions were assessed. We observed disruption of mitochondrial function and biogenesis and alteration in gene expression patterns in BSO-treated FRDA fibroblasts. Pre-treatment with adenosine ranging from 0–600 µM restored MMP, promoted ATP production and mitochondrial biogenesis, and modulated the expression of key metabolic genes, namely nuclear respiratory factor 1 (NRF1), transcription factor A, mitochondrial (TFAM), and NFE2-like bZIP transcription factor 2 (NFE2L2). Our study demonstrated that adenosine targeted mitochondrial defects in FRDA, contributing to improved mitochondrial function and biogenesis, leading to cellular iron homeostasis. Therefore, we suggest a possible therapeutic role for adenosine in FRDA.

Background and Objectives: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in the world. Transient receptor potential vanilloid 4 (TRPV4) channel has been shown to be involved in angiogenesis in multiple types of tumors. However, not much is known about TRPV4′s involvement in OSCC. Thus, in this study, we investigate the effect of administering a TRPV4 agonist on angiogenesis in OSCC. Materials and Methods: Thirty-six Sprague Dawley (SD) rats were used in this study. 4-nitroquinoline 1-oxide (4NQO) was used to induce OSCC. Cisplatin (an anticancer drug), and GSK1016790A (an agonist for TRPV4) was used in this study. Immunohistochemistry was employed to examine the TRPV4 expression. An RT² Profiler PCR Array was performed for gene expression analysis of TRPV4, vascular growth factors that correspond directly with angiogenesis, such as angiopoietin (Ang-1 and Ang-2), and tyrosine kinase (Tie-1 and Tie-2) receptors. Tumor vessel maturity was assessed by microvessel density and microvessel-pericyte-coverage index. Results: RT² profiler PCR array showed significant elevated levels of Ang-1 (2.1-fold change; p < 0.05) and Tie-2 (4.5-fold change; p < 0.05) in OSCC following the administration of a combination of GSK1016790A and cisplatin. Additionally, the combination treatment significantly reduced the microvessel density (p < 0.01) and significantly increased the percentage of microvessels covered with pericytes (p < 0.01) in OSCC. Furthermore, tumor size was significantly reduced (p < 0.05) in rats that received cisplatin alone. The combination treatment also greatly reduced the tumor size; however, the data were not statistically significant. Conclusions: The findings suggest that combining a TRPV4 agonist with cisplatin for treatment of OSCC promote vessels normalization via modulation of Ang-1/Tie-2 pathway.

Probiotics are gaining attention for their benefits as a supplement to improve oral health. This study aimed to evaluate the antibacterial effect of the probiotic Lactobacillus helveticus against Porphyromonas gingivalis, a significant pathogen in periodontal diseases. Antibacterial susceptibility was assessed using the well diffusion assay, with 0.12% chlorhexidine (CHX) served as the positive control. Biofilm biomass was evaluated using crystal violet staining. Cell viability in P. gingivalis treated with L. helveticus was determined using the LIVE/DEAD Baclight bacterial assay via fluorescence microscopy. Ultra-morphological alterations in these cells were further examined using Field Emission Scanning Electron Microscopy. The results indicated that L. helveticus significantly reduced the growth of P. gingivalis. The highest concentration of 10⁹ cells/mL achieved the most substantial inhibition in the well diffusion assay, followed by concentrations of 10⁸ cells/mL and 10⁷ cells/mL, which demonstrated a clear dose-dependent response. Furthermore, biofilms of P. gingivalis treated with L. helveticus exhibited a notable biomass reduction of up to 85% at the highest concentrations. LIVE/DEAD staining confirmed a decreased in cell viability among the treated populations, while FESEM analysis revealed morphological disruptions in P. gingivalis cells treated with L. helveticus. These findings suggest that L. helveticus has a potent antibacterial effect against P. gingivalis, highlighting the need for further research to identify the optimal probiotic strategies that could enhance periodontal health.

Background: Porphyromonas gingivalis is widely recognised as a periodontal pathogen. In recent years, there has been growing interest in the use of medicinal plant extracts as alternative treatments for periodontitis to combat the emergence of antibiotic-resistant bacteria. Ruta angustifolia L. Pers has been traditionally used to treat various ailments, including oral bacterial infections. However, the antimicrobial potential of R. angustifolia extracts against the periodontal pathogen P. gingivalis remains unexplored. Hence, the aim of this study was to investigate the antimicrobial activity of R. angustifolia extracts against P. gingivalis. Methods: The antimicrobial activity of R. angustifolia extracts (crude methanol, hexane and chloroform fractionated extracts) against P. gingivalis was evaluated using the well diffusion method. Additionally, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined. Biofilm biomass assessment and live/dead cell viability assays were performed to analyse the effect of R. angustifolia extracts. Ultrastructural morphological changes in P. gingivalis cells were determined using field emission scanning electron microscopy (FE-SEM). Results: It was found that P. gingivalis was susceptible to R. angustifolia extracts, with the chloroform fractionated extract exhibiting the highest inhibition zones. The MIC and MBC of chloroform fractionated extract were determined to be 6.25 mg/mL which substantially reduced P. gingivalis biofilm biomass. Live/dead cell viability assays showed the highest percentage of dead P. gingivalis cells after 48 h of incubation. FE-SEM confirmed that the chloroform fractionated extract effectively damaged the bacterial cell wall and altered the ultrastructural morphology of P. gingivalis. Conclusion: The results indicated that extracts of R. angustifolia has the potential to be used as an alternative treatment in addition to conventional periodontal therapies.