Photobiomodulation therapy drives massive epigenetic histone modifications, stem cells mobilization and accelerated epithelial healing.

Emerging evidence indicates the clinical benefits of photobiomodulation therapy (PBMT) in the management of skin and mucosal wounds. Here, we decided to explore the effects of different regiments of PBMT on epithelial cells and stem cells, and the potential implications over the epigenetic circuitry during healing. Scratch-wound migration, immunofluorescence (anti-acetyl-Histone H3, anti-acetyl-CBP/p300 and anti-BMI1), nuclear morphometry and western blotting (anti-Phospho-S6, anti-methyl-CpG binding domain protein 2 [MBD2]) were performed. Epithelial stem cells were identified by the aldehyde dehydrogenase enzymatic levels and sphere-forming assay. We observed that PBMT-induced accelerated epithelial migration and chromatin relaxation along with increased levels of histones acetylation, the transcription cofactors CBP/p300 and mammalian target of rapamycin. We further observed a reduction of the transcription repression-associated protein MBD2 and a reduced number of epithelial stem cells and spheres. In this study, we showed that PBMT could induce epigenetic modifications of epithelial cells and control stem cell fate, leading to an accelerated healing phenotype.

Propolis: A useful agent on psychiatric and neurological disorders? A focus on CAPE and pinocembrin components.

Propolis consists of a honeybee product, with a complex mix of substances that have been widely used in traditional medicine. Among several compounds present in propolis, caffeic acid phenethyl ester (CAPE), and pinocembrin emerge as two principal bioactive compounds, with benefits in a variety of body systems. In addition to its well-explored pharmacological properties, neuropharmacological activities have been poorly discussed. In an unprecedented way, the present review addresses the current finding on the promising therapeutic purposes of propolis, focusing on CAPE and pinocembrin, highlighting its use on neurological disturbance, as cerebral ischemia, neuroinflammation, convulsion, and cognitive impairment, as well as psychiatric disorders, such as anxiety and depression. In addition, we provide a critical analysis, discussion, and systematization of the molecular mechanisms which underlie these central nervous system effects. We hypothesize that the pleiotropic action of CAPE and pinocembrin, per se or associated with other substances present in propolis may result in the therapeutic activities reported. Inhibition of the pro-inflammatory cascade, antioxidant activity, and positive neurotrophic modulatory effects consist of the main molecular targets attributed to CAPE and pinocembrin in health benefits.

Epigenetic Modifications and Accumulation of DNA Double-Strand Breaks in Oral Lichen Planus Lesions Presenting Poor Response to Therapy.

Epigenetics refers to changes in cell characteristics that occur independently of modifications to the deoxyribonucleic acid (DNA) sequence. Alterations mediated by epigenetic mechanisms are important factors in cancer progression. Although an exciting prospect, the identification of early epigenetic markers associated with clinical outcome in premalignant and malignant disorders remains elusive. We examined alterations in chromatin acetylation in oral lichen planus (OLP) with distinct clinical behavior and compared the alterations to the levels of DNA double-strand breaks (DSBs). We analyzed 42 OLP patients, who had different responses to therapy, for acetyl-histone H3 at lys9 (H3K9ac), which is associated with enhanced transcription and nuclear decondensation, and the presence of DSBs, as determined by accumulation of phosphorylated γH2AX foci. Patients with high levels of H3K9ac acetylation failed to respond to therapy or experienced disease recurrence shortly after therapy. Similar to H3K9ac, patients who responded poorly to therapy had increased accumulation of DNA DSB, indicating genomic instability. These findings suggest that histone modifications occur in OLP, and H3K9ac and γH2AX histones may serve as epigenetic markers for OLP recurrence.

Healing action of topical chamomile on 5-fluoracil induced oral mucositis in hamster.

BACKGROUND: Oral mucositis is a common complication in the treatment of cancer. Its management and prevention are seen as high priority in cancer patient care. The aim of the present study was to investigate the effect of topical chamomile in the treatment of oral mucositis induced by 5-fluoracil (5-FU) in hamsters. MATERIALS AND METHODS: One hundred five hamsters were randomly separated into three groups (35 animals each): group I--without treatment (control); group II--treatment with chamomile (Ad-Muc®); and group III--treatment with corticoid (betamethasone elixir--Celestone®). The animals received an intraperitoneal injection of 5-FU on days 0 and 2. On days 3 and 4, the buccal mucosa was scratched and therapy was initiated on day 5. Three animals were sacrificed on days 0, 2, 5, 8, 10, 12, 14, and 16, weighed, and the buccal mucosa removed for clinical and histopathological analysis. RESULTS: The animals that developed mucositis and were treated with chamomile or the corticoid agent weighed significantly less than those in the control group. The group treated with the corticoid agent exhibited a more severe clinical condition, whereas the group treated with chamomile exhibited mild mucositis throughout the experiment. The group treated with chamomile had a 12-fold greater chance of scoring zero (absence of mucositis) than the control group. Analysis of the histopathological results demonstrated that the group treated with chamomile exhibited a lesser degree of mucositis throughout the evaluation period in comparison to the control and corticoid groups. CONCLUSION: Chamomile proved effective in the treatment of oral mucositis in a hamster model. However, well-designed clinical studies are needed to confirm the clinical efficacy of this medicine in humans.