Photobiomodulation effects on fibroblasts and keratinocytes after ionizing radiation and bacterial stimulus.

OBJECTIVE: Photobiomodulation therapy (PBMT) has proven to reduce inflammation and pain and increase wound healing. Thus, the aim of this study was to analyze the effects of PBMT parameters on migration, proliferation, and gene expression after ionizing radiation and bacterial-induced stress in an in vitro study. DESIGN: Keratinocytes (HaCaT) and Fibroblasts (HGFs) were grown in DMEM with 10 % fetal bovine serum until stressful condition induction with lipopolysaccharide (LPS) of Escherichia coli (1 µg/mL), Porphyromonas gingivalis protein extract (5 µg/mL) and ionizing radiation (8 Gy). Low-laser irradiation (660 nm, 30 mW) was carried out in four sessions, with 6 h intervals, and energy density of 2, 3, 4, and 5 J/cm². Scratch assays, immunofluorescence, and RT-qPCR were performed. RESULTS: Treated fibroblasts and keratinocytes showed significant response in proliferation and migration after scratch assays (p < 0.05). Higher expressions of α-SMA in fibroblasts and F-actin in keratinocytes were observed in cells subjected to 3 J/cm². PI3K-pathway genes expression tended to enhance in fibroblasts, presenting a higher relative expression when compared to keratinocytes. In keratinocytes, PBMT groups demonstrated deregulated expression for all inflammatory cytokines' genes tested while fibroblasts presented a tendency to enhance those genes expression in a dose dependent way. CONCLUSIONS: The present study showed that delivering 660 nm, 30 mW was effective to stimulate cell migration, proliferation and to accelerate wound healing. PBMT can modulate cytokines and pathways involved in wound repair. The different energy densities delivering distinct responses in vitro highlights that understanding laser parameters is fundamental to improve treatment strategies.

Effects of oral supplementation to manage radiation dermatitis in cancer patients: a systematic review.

PURPOSE: To evaluate the effectiveness and safety of oral supplementation as a radioprotective intervention in the management of radiation dermatitis (RD). METHODS: Systematic review and meta-analysis. Six databases and the gray literature were searched for randomized controlled clinical trials (RCTs). Meta-analysis was performed only with studies that evaluated the same intervention. Methodology of included studies was evaluated by the Cochrane risk-of-bias tool for randomized trials (RoB 2.0), and the certainty of evidence was assessed by the GRADE instrument. RESULTS: Seventeen RCTs were included in this review. These evaluated different types of oral supplementations. Findings from three meta-analyses demonstrated no significant benefits to the more severe grades of RD, as oral curcuminoids (RR, 0.59; 95% CI, 0.27 to 1.29; P = 0.19; I2 = 88%), glutamine (RR, 0.40; 95% CI, 0.15 to 1.03; P = 0.06; I2 = 78%) or Wobe-Mugos (RR, 0.57; 95% CI, 0.29 to 1.14; P = 0.11; I2 = 72%). Also, the certainty of the evidence of outcomes evaluated was moderate or low. Except for a few gastrointestinal adverse events, oral supplementation was well tolerated. CONCLUSION: Most oral supplements cannot yet be recommended to manage RD due to insufficient or conflicting evidence. However, despite no significant results, glutamine was shown to be a promising substance in terms of the potential radioprotective effect and may be well tolerated. These results suggest that more RCTs with larger samples are needed to evaluate the efficacy, safety, and tolerance of glutamine in the management of RD.

Use of Chamomile Infusion to Mitigate Radiotherapy-Induced Dry Desquamation in Head and Neck Cancer Patients.

PURPOSE: To evaluate the effect of using a compress with Chamomilla recutita infusion in the regression of dry desquamation and in the prevention of moist desquamation in head and neck cancer patients undergoing radiotherapy. METHODS: A prospective intervention study was carried out from May 2019 to May 2021. In total, 43 participants were included, who were instructed to apply the compress with the infusion 3 times a day, after occurrence of dry desquamation. Skin evaluation took place daily from initiation of the intervention up to the end of radiotherapy. RESULTS: All the participants presented dry desquamation regression, where 65.1% (95% CI 50.1-78.1) had total regression until the end of radiotherapy, with a mean of 9 days of regression. Only 34.9% (95% CI 21.8-49.9) of the participants developed moist desquamation by the end of the radiotherapy sessions, with a mean accumulated dose of ionizing radiation of 50.9 Gy. CONCLUSION: This study highlighted the potential clinical benefits of using Chamomilla recutita in the regression of dry desquamation and in the prevention of moist desquamation.

Effects of medicinal plants and natural compounds in models of prostate cancer related to sex steroids: A systematic review.

Prostate cancer remains a health problem for men. Targeting androgen (AR) and estrogen (ER) receptors improves the outcomes of the disease, and many medicinal plants exert their effects by modulating these pathways. Therefore, a systematic review was conducted to identify medicinal plants and their natural compounds that may modulate the AR and/or ER pathways in cell and animal models. A search was conducted across EMBASE, LILACS, PubMed, Scopus, and Web of Science, with grey literature from Google SCHOLAR and ProQuest. Two authors independently selected eligible studies based on their titles and abstracts, and a third author resolved conflicts. Then, data from the full text of eligible studies were extracted and synthesized. In total, 75 studies were included. Results showed the effects of several different medicinal plants and natural compounds in reduction of AR and/or ER transcription and translation and AR secondary effects: cell growth reduction, induction of apoptosis, and cell cycle arrest. In animal models, tumor size reduction, increase in apoptosis, and downregulation of AR expression in tumors were also observed. No single phytochemical group concentrating molecules with anti-AR and/or ER activity was identified. Nevertheless, several phytochemical compounds showed potential for future clinical studies in the management of the disease.

Effectiveness of photobiomodulation therapy in radiation dermatitis: A systematic review and meta-analysis.

PURPOSE: To evaluate the effectiveness of photobiomodulation therapy (PBMT) in the prevention and treatment of radiation dermatitis (RD). METHODS: A systematic review was conducted using seven databases and the gray literature. We performed a meta-analysis to summarize the effect sizes of response rates (RRs). RESULTS: We included seven clinical trials. Breast cancer patients receiving PBMT developed more grade 1 RD than the control group (RR 1.55, 95 % CI 1.14-2.10, I2 = 51 %). PBMT appears to prevent RD grade 2 (RR 0.33, 95 % CI 0.09-1.23, I2 = 85 %) and RD grade 3 (RR 0.21, 95 % CI 0.05-0.94, I2 = 0%) with very low certainty of evidence. CONCLUSIONS: There is very low certainty of evidence that PBMT was effective in the prevention of RD. However, PBMT showed a significant effect to prevent grade 3 RD in breast cancer patients. Thus, further randomized clinical trials are required to confirm the promising effect of PBMT in RD.

Curcumin downregulates the PI3K-AKT-mTOR pathway and inhibits growth and progression in head and neck cancer cells.

Curcumin, a polyphenol isolated from the rhizome of Curcuma longa, has been studied because of its antioxidant, antimicrobial, and antiinflammatory properties. This study aimed to evaluate the effects of curcumin on head and neck cancer (HNC) cell lines and how it modulates the PI3K-AKT-mTOR signaling pathway. Dose-response curves for curcumin were established for hypopharynx carcinoma (FaDu), tongue carcinoma (SCC-9), and keratinocytes (HaCaT) cell lines and IC50 values were calculated. Cell cycle and cell death were investigated through flow cytometry. Cytoskeleton organization was assessed through phalloidin+FITC staining. qPCR array and western blot were performed to analyze gene and protein expression. Curcumin reduced cell viability in a dose-dependent and selective manner, induced cell death on SCC-9 cells (necrosis/late apoptosis: 44% curcumin vs. 16.4% vehicle), and arrested cell cycle at phase G2 /M on SCC-9 and FaDu (G2 : SCC-9-19.1% curcumin vs. 13.4% vehicle; FaDu-37.8% curcumin vs. 12.9% vehicle). Disorganized cytoskeleton and altered cell morphology were observed. Furthermore, curcumin downregulated the PI3K-AKT-mTOR signaling pathway by modifying the expression of key genes and proteins. These findings highlight the promising therapeutic potential of curcumin to inhibit HNC growth and progression and to modulate the PI3K-AKT-mTOR pathway.

Laser therapy for recurrent aphthous stomatitis: an overview.

OBJECTIVES: To evaluate therapeutic effects of laser therapy on patients with recurrent aphthous stomatitis assessing evidences from previously published systematic reviews. MATERIALS AND METHODS: An overview of systematic reviews was conducted based on PRISMA checklist. Search strategies were developed and adapted for six different electronic databases and a gray literature search was also performed. The methodology quality of the included systematic reviews was assessed by the Measurement Tool to Assess the Methodological Quality of Systematic Reviews 2 (AMSTAR 2). RESULTS: After a two-step selection, five systematic reviews were included. Methodology quality was considered as a high risk of bias in two systematic reviews, while in the other three were graded as moderate. The systematic reviews' conclusions demonstrated that all included systematics reviews showed positive effects of laser therapy for pain relief, and most of them demonstrated healing improvement. A meta-analysis was not feasible due to heterogeneity in treatments parameters. CONCLUSIONS: Evidence suggested that laser therapy is an effective tool to treat recurrent aphthous stomatitis; nevertheless, more randomized clinical trials should be conducted to compare different lasers parameters. CLINICAL RELEVANCE: The present overview evaluated recent evidence about laser therapy for recurrent aphthous stomatitis management in order to contribute for evidence-based dentistry and decision-making. This overview suggests that laser therapy is a safe and promising alternative to treat recurrent aphthous stomatitis, since it promotes wound healing and pain relief.

Effects of oral supplementation in the management of oral mucositis in cancer patients: A meta-analysis of randomized clinical trials.

PURPOSE: To evaluate the effects of oral supplementation on the management of oral mucositis in patients with cancer undergoing chemo and/or radiation therapy. METHOD: This is a systematic review and meta-analysis. The search was performed at 6 databases, and in the gray literature. Methodology of included studies was evaluated by the Cochrane Collaboration Risk of Bias Tool, and evidence quality was assessed by GRADE instrument. RESULTS: Twelve randomized clinical trials were included in this review. The oral supplementation used was an oral elemental diet with amino acids and minerals (elental), glutamine, and zinc. The majority of the studies included in this review showed benefits in delaying the occurrence of OM by using glutamine and zinc, and in reducing the severity of OM with glutamine, zinc, and elental in patients receiving chemoradiotherapy. The meta-analysis showed that the risk of oral mucositis in the zinc group was slightly lower than in the control (RR: 0.71, 95% CI: 0.53-0.96, P = 0.02, n = 982) while the glutamine group presented the same risk as the control (RR: 0.91, 95% CI: 0.78-1.05, P = 0.19, n = 314). The evidence quality suggested low confidence for zinc and glutamine studies in the estimated effect from the outcomes assessed. CONCLUSIONS: Zinc is a promising strategy in the management of oral mucositis since it delayed the occurrence and reduced its severity. Glutamine and Elental, on the other hand, had no strong evidence in the prevention and/or treatment of oral mucositis in patients with cancer.

In vitro evaluation of Eugenia dysenterica in primary culture of human gingival fibroblast cells.

Eugenia dysenterica is a Brazilian tree investigated for its properties and bioactive compounds, which are believed to have both pharmacological and phytochemical therapeutic effects. The leaves of this tree contain tannins, flavonoids, terpenes, and saponins, with reportedly beneficial effects to the human body. Despite these therapeutic applications, its effects have never been tested on oral tissues. Therefore, the aim of the present study was to evaluate the cytotoxic and antioxidant effects and the anti-inflammatory and repair properties of the acetone fraction of E. dysenterica on primary culture of human gingival fibroblasts and on the immortalized murine macrophage cell line (RAW 264.7). For this purpose, a metabolic activity assay, a wound healing assay, a nitric oxide assay, and RT-qPCR were performed. The assays revealed a cytoprotective effect of this plant, suggested by the increase in the expression of SOD1 and NRF2. An antioxidant potential effect was observed in the DPPH• assay. However, the fraction of E. dysenterica did not show anti-inflammatory activity. In conclusion, Eugenia dysenterica may promote cytoprotection when associated with chlorhexidine digluconate because of its antioxidant effect. However, additional studies are necessary on other human dental tissues using other parts of the plant in order to develop a possible mouthwash to assist patients with oral disorders.

Effects of turmeric and curcumin on oral mucositis: A systematic review.

The aim of this study was to evaluate the effects of turmeric and curcumin in the management of oral mucositis in cancer patients undergoing chemo and/or radiotherapy. The systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses. The search was performed in the following database: Cochrane Library, LILACS, LIVIVO, PubMed, Scopus, and Web of Science. A gray literature search was undertaken using Google Scholar, Open Grey, and ProQuest. The methodology of included studies was evaluated by the Meta-Analysis of Statistics Assessment and Review Instrument. After a two-step selection process, four randomized and one nonrandomized clinical trials were included in the analysis. Two studies were categorized as low and three as moderate risk of bias. Turmeric/curcumin was applied topically as a gel or as a mouthwash. Patients treated with turmeric/curcumin experienced reduced grade of mucositis, pain, erythema intensity, and ulcerative area. Current evidence suggests that topical application of turmeric or curcumin is effective in controlling signs and symptoms of oral mucositis. Thus, further investigation is required to confirm the promising effect of turmeric and curcumin in oral inflammatory lesions.

In vitro evaluation of wound healing and antimicrobial potential of ozone therapy.

Although ozone therapy is extensively applied when wound repair and antimicrobial effect are necessary, little is known about cellular mechanisms regarding this process. Thus, this study aimed to evaluate ozone cytotoxicity in fibroblasts (L929) and keratinocytes (HaCaT) cell lines, its effects on cell migration and its antimicrobial activity. Cells were treated with ozonated phosphate-buffered saline (8, 4, 2, 1, 0.5 and 0.25 µg/mL ozone), chlorhexidine 0.2% or buffered-solution, and cell viability was determined through MTT assay. The effect of ozone on cell migration was evaluated through scratch wound healing and transwell migration assays. The minimum inhibitory concentrations for Candida albicans and Staphylococcus aureus were determined. Ozone showed no cytotoxicity for the cell lines, while chlorhexidine markedly reduced cell viability. Although no significant difference between control and ozone-treated cells was observed in the scratch assay, a considerable increase in fibroblasts migration was noticed on cells treated with 8 µg/mL ozonated solution. Ozone alone did not inhibit growth of microorganisms; however, its association with chlorhexidine resulted in antimicrobial activity. This study confirms the wound healing and antimicrobial potential of ozone therapy and presents the need for studies to elucidate the molecular mechanisms through which it exerts such biological effects.

In vivo and in vitro effects of curcumin on head and neck carcinoma: a systematic review.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) contributes globally to a great number of deaths and morbidity, in spite of new therapeutic strategies. There is a great need of new drugs that are significantly effective and less deleterious to the patients' general health. In this sense, phytotherapy is a tendency, with results pointing to its use as a chemo-preventive and adjuvant therapy. Therefore, the objective of this systematic review was to investigate the effects of curcumin on proliferation and survival of HNSCC. MATERIALS AND METHODS: The search was conducted on six databases: Cochrane, LILACS, EMBASE, MEDLINE, PubMed, and Web of Science. In vitro and in vivo studies that evaluated the effects of curcumin on cell viability, tumor growth, cell cycle and/or cell death pattern in HNSCC cell lines or animal models were selected. RESULTS: Of the 525 initially gathered studies, 30 met the inclusion criteria. These studies demonstrated that curcumin induces cytotoxicity, apoptosis (via intrinsic pathway), and cell cycle arrest in G2 /M phase in HSNCC cell lines. It also reduces tumor measurements in animal models. These events were mostly studied through MTT assay, flow cytometry, and cell cycle- and apoptosis-related proteins expression. CONCLUSION: This systematic review demonstrated that curcumin is effective on HNSCC cell proliferation and survival, reinforcing the currently available evidence that curcumin could be an adjuvant drug in HNSCC treatment.

Effects of Plants on Osteogenic Differentiation and Mineralization of Periodontal Ligament Cells: A Systematic Review.

This systematic review aimed to evaluate the effects of plants on osteogenic differentiation and mineralization of human periodontal ligament cells. The included studies were selected using five different electronic databases. The reference list of the included studies was crosschecked, and a partial gray literature search was undertaken using Google Scholar and ProQuest. The methodology of the selected studies was evaluated using GRADE. After a two-step selection process, eight studies were identified. Six different types of plants were reported in the selected studies, which were Morinda citrifolia, Aloe vera, Fructus cnidii, Zanthoxylum schinifolium, Centella asiatica, and Epimedium species. They included five types of isolated plant components: acemannan, osthole, hesperetin, asiaticoside, and icariin. In addition, some active substances of these components were identified as polysaccharides, coumarins, flavonoids, and triterpenes. The studies demonstrated the potential effects of plants on osteogenic differentiation, cell proliferation, mineral deposition, and gene and protein expression. Four studies showed that periodontal ligament cells induce mineral deposition after plant treatment. Although there are few studies on the subject, current evidence suggests that plants are potentially useful for the treatment of periodontal diseases. However, further investigations are required to confirm the promising effect of these plants in regenerative treatments.

Plants from Brazilian Cerrado with potent tyrosinase inhibitory activity.

The increased amount of melanin leads to skin disorders such as age spots, freckles, melasma and malignant melanoma. Tyrosinase is known to be the key enzyme in melanin production. Plants and their extracts are inexpensive and rich resources of active compounds that can be utilized to inhibit tyrosinase as well as can be used for the treatment of dermatological disorders associated with melanin hyperpigmentation. Using in vitro tyrosinase inhibitory activity assay, extracts from 13 plant species from Brazilian Cerrado were evaluated. The results showed that Pouteria torta and Eugenia dysenterica extracts presented potent in vitro tyrosinase inhibition compared to positive control kojic acid. Ethanol extract of Eugenia dysenterica leaves showed significant (p<0.05) tyrosinase inhibitory activity exhibiting the IC50 value of 11.88 µg/mL, compared to kojic acid (IC50 value of 13.14 µg/mL). Pouteria torta aqueous extract leaves also showed significant inhibitory activity with IC50 value of 30.01 µg/mL. These results indicate that Pouteria torta and Eugenia dysenterica extracts and their isolated constituents are promising agents for skin-whitening or antimelanogenesis formulations.

Macroscopic and microscopic effects of GaAIAs diode laser and dexamethasone therapies on oral mucositis induced by fluorouracil in rats.

PURPOSE: To present an animal model for mucositis induced by fluorouracil in rats, and test two therapeutic options, the GaAIAs laser and topical dexamethasone, analysing them with regard to the quality and quantity of tissue alterations and comparing them with the phases of mucositis. MATERIALS AND METHODS: Forty-five Wistar rats (250 g) were treated with fluorouracil (60 mg/kg) and, in order to mimic the clinical effect of chronic irritation, the palatal mucosa was irritated by superficial scratching with an 18-gauge needle. When all of the rats presented oral ulcers of mucositis, they were randomly allocated to one of three groups: group I was treated with laser (GaAIAs), group II was treated with topical dexamethasone, and group III was not treated. Excisional biopsies of the palatal mucosa were then performed, and the rats were killed. Tissue sections were stained with haematoxylin and eosin for morphological analyses, and with toluidine blue for mast-cell counts. RESULTS: Group I specimens showed higher prevalence of ulcers, bacterial biofilm, necrosis and vascularisation, while group II specimens showed higher prevalance of granulation tissue formation. There were no significant statistical differences in the numbers of mast cells and epithelial thickness between groups. CONCLUSION: For the present model of mucositis, rats with palatal mucositis treated with laser (GaAIAs) showed characteristics compatible with the ulcerative phase of oral mucositis, and rats treated with topical dexamethasone showed characteristics compatible with the healing phase of mucositis. Topical dexamethasone was more efficient in the treatment of rats' oral mucositis than the laser.