Necroptosis as a consequence of photodynamic therapy in tumor cells.

Photodynamic therapy (PDT) is an alternative to cancer treatment, demonstrating selectivity and significant cytotoxicity on malignant tissues. Such therapy involves two nontoxic components: photosensitizer (PS) and non-ionizing radiation. In optimal dosage combinations, PDT causes cellular and tissue effects by oxygen-dependent processes, leading tumor cells to regulated cell death pathways. Regulated necrosis, called necroptosis, can be triggered by PDT and is characterized by caspase-8 inhibition and RIPK1, RIPK3, and MLKL activities, leading to plasma membrane pores formation with subsequent cellular content release into the extracellular space. For this review, studies accessed by PubMed describing the relation between necroptosis and PDT were summarized. The results showed that PDT can trigger necroptosis mechanisms in different tumor cells. Moreover, a mix of different cell death types can co-occur. It is also important to highlight that necroptosis triggered by PDT is related to damage-associated molecular patterns (DAMPs) release, involving immunogenic cell death and vaccination. The cell death response is directly related to the photosensitizer chemical characteristics, concentration, incubation time, cellular location, and irradiation parameters. The synergism among all cell death types is an excellent advantage for avowing tumor resistance mechanisms and developing new solutions.

APX2009 sensitizes hypoxic breast cancer cells to doxorubicin by increasing its accumulation and caspase-3/7-mediated apoptosis.

PURPOSE: The association of targeted therapy with chemotherapy is encouraged to increase the treatment efficiency, especially in hypoxic triple-negative breast cancer. The APE1 redox activity has stood out as a potential tumor target. However, the effect of the association of the APE1 redox inhibitors with doxorubicin in hypoxia still needs to be evidenced. Therefore, our objective was to investigate the effect of the APX2009 (APE1 inhibitor) on the sensitization of breast cancer cells to doxorubicin in normoxia and hypoxia. METHODS: The WST-1 assay was used to evaluate cell viability after APX2009 and doxorubicin application under normoxia and hypoxia conditions in the MCF-7 and MDA-MB-231 cells. Apoptosis was analyzed by annexin assay and detection of caspases-3/7 activity by luminescence-based assay. The clinical association between APE1 inhibition signature and doxorubicin sensitivity was evaluated by bioinformatics analyses. RESULTS: MDA-MB-231 and MCF-7 cell lines were more sensitive to APX2009 in normoxia than in hypoxia. Co-treatment with APX2009 and doxorubicin in hypoxia further decreased the viability of triple-negative MDA-MB-231 cells than treatment alone, which was accompanied by doxorubicin intracellular accumulation, and increase of apoptotic cells percentage, and caspases-3/7 activity. Moderate association was found between APE1 inhibition signature and doxorubicin sensitivity in the hypoxic basal subtype. CONCLUSION: The findings suggest that APX2009 sensitizes the MDA-MB-231 cells to doxorubicin in hypoxia by doxorubicin intracellular accumulation and caspases-3/7-mediated apoptosis.

Low-power red laser and blue LED modulate telomere maintenance and length in human breast cancer cells.

Cancer cells have the ability to undergo an unlimited number of cell divisions, which gives them immortality. Thus, the cancer cell can extend the length of its telomeres, allowing these cells to divide unlimitedly and avoid entering the state of senescence or cellular apoptosis. One of the main effects of photobiomodulation (PBM) is the increase in the production of adenosine triphosphate (ATP) and free radicals, mainly reactive oxygen species (ROS). Existent data indicates that high levels of ROS can cause shortening and dysfunctional telomeres. Therefore, a better understanding of the effects induced by PBM on cancer cell telomere maintenance is needed. This work aimed to evaluate the effects of low-power red laser (658 nm) and blue LED (470 nm) on the TRF1 and TRF2 mRNA levels and telomere length in human breast cancer cells. MCF-7 and MDA-MB-231 cells were irradiated with a low-power red laser (69 J cm-2, 0.77 W/cm-2) and blue LED (482 J cm-2, 5.35 W/cm-2), alone or in combination, and the relative mRNA levels of the genes and telomere length were assessed by quantitative reverse transcription polymerase chain reaction. The results suggested that exposure to certain red laser and blue LED fluences decreased the TRF1 and TRF2 mRNA levels in both human breast cancer cells. Telomere length was increased in MCF-7 cells after exposure to red laser and blue LED. However, telomere length in MDA-MB-231 was shortened after exposure to red laser and blue LED at fluences evaluated. Our research suggests that photobiomodulation induced by red laser and low-power blue LED could alter telomere maintenance and length.

STAT3 Regulates the Redox Profile in MDA-MB-231 Breast Cancer Cells.

Unbalanced redox status and constitutive STAT3 activation are related to several aspects of tumor biology and poor prognosis, including metastasis and drug resistance. The triple-negative breast cancer (TNBC) is listed as the most aggressive and exhibits the worst prognosis among the breast cancer subtypes. Although the mechanism of reactive oxygen species (ROS) generation led to STAT3 activation is described, there is no data concerning the STAT3 influence on redox homeostasis in TNBC. To address the role of STAT3 signaling in redox balance, we inhibited STAT3 in TNBC cells and investigated its impact on total ROS levels, contents of hydroperoxides, nitric oxide (NO), and total glutathione (GSH), as well as the expression levels of 3-nitrotyrosine (3NT), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and nuclear factor kappa B (NF-κB)/p65. Our results indicate that ROS levels depend on the STAT3 activation, while the hydroperoxide level remained unchanged, and NO and 3NT expression increased. Furthermore, GSH levels, Nrf2, and NF-κB/p65 protein levels are decreased in the STAT3-inhibited cells. Accordingly, TNBC patients' data from TCGA demonstrated that both STAT3 mRNA levels and STAT3 signature are correlated to NF-κB/p65 and Nrf2 signatures. Our findings implicate STAT3 in controlling redox balance and regulating redox-related genes' expression in triple-negative breast cancer.

Effects of low­power red laser and blue LED on mRNA levels from DNA repair genes in human breast cancer cells.

Photobiomodulation (PBM) induced by non-ionizing radiations emitted from low-power lasers and light-emitting diodes (LEDs) has been used for various therapeutic purposes due to its molecular, cellular, and systemic effects. At the molecular level, experimental data have suggested that PBM modulates base excision repair (BER), which is responsible for restoring DNA damage. There is a relationship between the misfunction of the BER DNA repair pathway and the development of tumors, including breast cancer. However, the effects of PBM on cancer cells have been controversial. Breast cancer (BC) is the main public health problem in the world and is the most diagnosed type of cancer among women worldwide. Therefore, the evaluation of new strategies, such as PBM, could increase knowledge about BC and improve therapies against BC. Thus, this work aims to evaluate the effects of low-power red laser (658 nm) and blue LED (470 nm) on the mRNA levels from BER genes in human breast cancer cells. MCF-7 and MDA-MB-231 cells were irradiated with a low-power red laser (69 J cm-2, 0.77 W cm-2) and blue LED (482 J cm-2, 5.35 W cm-2), alone or in combination, and the relative mRNA levels of the APTX, PolB, and PCNA genes were assessed by reverse transcription-quantitative polymerase chain reaction. The results suggested that exposure to low-power red laser and blue LED decreased the mRNA levels from APTX, PolB, and PCNA genes in human breast cancer cells. Our research shows that photobiomodulation induced by low-power red laser and blue LED decreases the mRNA levels of repair genes from the base excision repair pathway in MCF-7 and MDA-MB-231 cells.

The APE1/REF-1 and the hallmarks of cancer.

APE1/REF-1 (apurinic/apyrimidinic endonuclease 1 / redox factor-1) is a protein with two domains, with endonuclease function and redox activity. Its main activity described is acting in DNA repair by base excision repair (BER) pathway, which restores DNA damage caused by oxidation, alkylation, and single-strand breaks. In contrast, the APE1 redox domain is responsible for regulating transcription factors, such as AP-1 (activating protein-1), NF-κB (Nuclear Factor kappa B), HIF-1α (Hypoxia-inducible factor 1-alpha), and STAT3 (Signal Transducers and Activators of Transcription 3). These factors are involved in physiological cellular processes, such as cell growth, inflammation, and angiogenesis, as well as in cancer. In human malignant tumors, APE1 overexpression is associated with lung, colon, ovaries, prostate, and breast cancer progression, more aggressive tumor phenotypes, and worse prognosis. In this review, we explore APE1 and its domain's role in cancer development processes, highlighting the role of APE1 in the hallmarks of cancer. We reviewed original articles and reviews from Pubmed related to APE1 and cancer and found that both domains of APE1/REF-1, but mainly its redox activity, are essential to cancer cells. This protein is often overexpressed in cancer, and its expression and activity are correlated to processes such as proliferation, invasion, inflammation, angiogenesis, and resistance to cell death. Therefore, APE1 participates in essential processes of cancer development. Then, the activity of APE1/REF-1 in these hallmarks suggests that targeting this protein could be a good therapeutic approach.

Could violet-blue lights increase the bacteria resistance against ultraviolet radiation mediated by photolyases?

Studies have demonstrated bacterial inactivation by radiations at wavelengths between 400 and 500 nm emitted by low-power light sources. The phototoxic activity of these radiations could occur by oxidative damage in DNA and membrane proteins/lipids. However, some cellular mechanisms can reverse these damages in DNA, allowing the maintenance of genetic stability. Photoreactivation is among such mechanisms able to repair DNA damages induced by ultraviolet radiation, ranging from ultraviolet A to blue radiations. In this review, studies on the effects of violet and blue lights emitted by low-power LEDs on bacteria were accessed by PubMed, and discussed the repair of ultraviolet-induced DNA damage by photoreactivation mechanisms. Data from such studies suggested bacterial inactivation after exposure to violet (405 nm) and blue (425-460 nm) radiations emitted from LEDs. However, other studies showed bacterial photoreactivation induced by radiations at 348-440 nm. This process occurs by photolyase enzymes, which absorb photons at wavelengths and repair DNA damage. Although authors have reported bacterial inactivation after exposure to violet and blue radiations emitted from LEDs, pre-exposure to such radiations at low fluences could activate the photolyases, increasing resistance to DNA damage induced by ultraviolet radiation.

Effects of photobiomodulation by low-power lasers and LEDs on the viability, migration, and invasion of breast cancer cells.

Among the malignant tumors, breast cancer is the most commonly diagnosed worldwide, being the most prevalent in women. Photobiomodulation has been used for wound healing, swelling and pain reduction, and muscle repair. The application of photobiomodulation in cancer patients has been controversial. Therefore, a better understanding of radiation-induced effects involved in photobiomodulation on cancer cells is needed. Thus, this study aimed to investigate the effects of exposure to low-power lasers and LEDs on cell viability, migration, and invasion in human breast cancer cells. MCF-7 and MDA-MB-231 cells were irradiated with a low-power red laser (23, 46, and 69 J/cm2, 0.77 W/cm2) and blue LED (160, 321, and 482 J/cm2, 5.35 W/cm2), alone or in combination. Cell viability was assessed using the WST-1 assay, cell migration was evaluated using the wound healing assay, and cell invasion was performed using the Matrigel transwell assay. Viability and migration were not altered in MCF-7 and MDA-MB-231 cultures after exposure to low-power red laser and blue LED. However, there was a decrease in cell invasion from the cultures of the two cell lines evaluated. The results suggest that photobiomodulation induced by low-power red laser and blue LED does not alter cell viability and migration but decreases cell invasion in human breast cancer cells.

Mitochondria in colorectal cancer stem cells - a target in drug resistance.

Colorectal cancer (CRC) is the third most diagnosed cancer and the second most deadly type of cancer worldwide. In late diagnosis, CRC can resist therapy regimens in which cancer stem cells (CSCs) are intimately related. CSCs are a subpopulation of tumor cells responsible for tumor initiation and maintenance, metastasis, and resistance to conventional treatments. In this scenario, colorectal cancer stem cells (CCSCs) are considered an important key for therapeutic failure and resistance. In its turn, mitochondria is an organelle involved in many mechanisms in cancer, including chemoresistance of cytotoxic drugs due to alterations in mitochondrial metabolism, apoptosis, dynamics, and mitophagy. Therefore, it is crucial to understand the mitochondrial role in CCSCs regarding CRC drug resistance. It has been shown that enhanced anti-apoptotic protein expression, mitophagy rate, and addiction to oxidative phosphorylation are the major strategies developed by CCSCs to avoid drug insults. Thus, new mitochondria-targeted drug approaches must be explored to mitigate CRC chemoresistance via the ablation of CCSCs.

Profiles of Expression of SAV1 in Normoxia or Hypoxia Microenviroment are Associated with Breast Cancer Prognosis.

BACKGROUND: In breast cancer (BC), hypoxia is associated with poor prognosis. Protein Salvador homolog 1 (SAV1) acts as a tumor suppressor and is downregulated in the cancer cells. However, there is limited data on the expression profile of SAV1 and its importance in BC. It has not been studied to evaluate this phenomenon in a hypoxic microenvironment yet. AIM: This study aimed to investigate SAV1 expression profiles under normoxia and hypoxia, and the potential of SAV1 in BC prognosis. METHODS: Gene and protein expression analyses were performed using Real-Time quantitative PCR (RT-qPCR) and immunocytochemistry (ICC), respectively, and in silico analyses were performed using The Cancer Genome Atlas (TCGA). The survival curves were constructed using KMplotter. RESULTS: SAV1 expression was lower in BC samples and tumor cell lines than in normal samples. The SAV1 mRNA levels were reduced in hypoxic estrogen receptor positive (ER+) tumors, which were associated with a lower survival probability as compared to normoxic ER+ tumors. Furthermore, lower levels of SAV1 were found in advanced cancer stage samples, which are associated with worse survival curves and can be a risk factor for BC. CONCLUSIONS: These data suggest a potential prognostic role of SAV1 in BC, with lower expressions associated with worse prognosis.

An Overview Regarding Pharmacogenomics and Biomarkers Discovery: Focus on Breast Cancer.

Breast cancer represents a health concern worldwide for being the leading cause of cancer- related women's death. The main challenge for breast cancer treatment involves its heterogeneous nature with distinct clinical outcomes. It is clinically categorized into five subtypes: luminal A; luminal B, HER2-positive, luminal-HER, and triple-negative. Despite the significant advances in the past decades, critical issues involving the development of efficient target-specific therapies and overcoming treatment resistance still need to be better addressed. OMICs-based strategies have marked a revolution in cancer biology comprehension in the past two decades. It is a consensus that Next-Generation Sequencing (NGS) is the primary source of this revolution and the development of relevant consortia translating pharmacogenomics into clinical practice. Still, new approaches, such as CRISPR editing and epigenomic sequencing are essential for target and biomarker discoveries. Here, we discuss genomics and epigenomics techniques, how they have been applied in clinical management and to improve therapeutic strategies in breast cancer, as well as the pharmacogenomics translation into the current and upcoming clinical routine.

Low-power therapeutic lasers on mRNA levels.

Gene expression evaluation in cells and biological tissues has been crucial for research in biology, medicine, biotechnology, and diagnostic. Messenger ribonucleic acid (mRNA) levels show relationship with gene expression, and they can be measured by real-time quantitative polymerase chain reaction (RT-qPCR) for the quantification of steady-state mRNA levels in cells and biological tissues. Radiations emitted from low-power lasers induce photobiomodulation, which is the base of therapeutic protocols for disease treatment. Despite that the understanding on photobiomodulation has been improved by mRNA level evaluation, laser irradiation parameters and procedures are diversified among studies, harming the comparison of RT-qPCR data. In this systematic review, data from mRNA levels reported in photobiomodulation studies were summarized regarding the process, function, and gene. Literature search was conducted for the assessment of published reports on mRNA levels evaluated by RT-qPCR in cells and biological tissues exposed to low-power lasers. Data showed that mRNA levels have been evaluated by RT-qPCR for a variety of genes related to molecular, cellular, and systemic processes after low-power violet-orange, red, and infrared laser exposure. Results from gene expression have increased the understanding of the mechanisms involved in photobiomodulation, and they can be useful to increase the efficacy and safety of clinical applications based on low-power lasers.

Hypoxia effects on cancer stem cell phenotype in colorectal cancer: a mini-review.

Colorectal cancer (CRC) is ranked third most incident and second most deadly around the world, and even though treatments significantly developed over the years, overall survival remains low. This scenario has the contribution of cancer stem cells (CSC), a subpopulation of the heterogeneous tumor bulk, considered to be responsible for the tumor maintenance, conventional therapies resistance, metastasis, and recurrence. In this regard, hypoxia appears as an important component of tumor microenvironment and CSC niche, being associated with a worse prognosis. Therefore, it is vital the study of hypoxia influence on CSC phenotype in CRC. The aim of this mini-review article is to present a brief overview on this field. Recent articles discoursed about CSC molecular regulation, signalling pathways, methods for the study of the topic, as well as molecules and drugs capacity of inhibiting the interplay of hypoxia-CSC. Finally, the studies demonstrated important results, extensively accessing the topics of cellular and molecular regulation and therapeutic intervention, being morphology an area to be more explored.

High-Resolution Melting Analysis for Rapid Detection of Mutations in Patients with FGFR3-Related Skeletal Dysplasias.

Background: Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene are related to skeletal dysplasias (SDs): acondroplasia (ACH), hypochodroplasia (HCH) and type I (TDI) and II (TDII) tanatophoric dysplasias. This study was designed to standardize and implement a high-resolution melting (HRM) technique to identify mutations in patients with these phenotypes. Methods: Initially, FGFR3 gene segments from 84 patients were PCR amplified and subjected to Sanger sequencing. Samples from 29 patients positive for mutations were analyzed by HRM. Results: Twelve of the patients FGFR3 mutations had ACH (six g.16081 G > A, three g.16081 G > C and three g.16081 G > A + g.16002 C > T); thirteen of patients with HCH had FGFR3 mutations (eight g.17333 C > A, five g.17333 C > G and five were negative); and four patients with DTI had FGFR3 mutations (three g.13526 C > T and one g.16051G > T and two patients with DTII (presented mutation g.17852 A > G). When analyzing the four SDs altogether, an overlap of the dissociation curves was observed, making genotyping difficult. When analyzed separately, however, the HRM analysis method proved to be efficient for discriminating among the mutations for each SD type, except for those patients carrying additional polymorphism concomitant to the recurrent mutation. Conclusion: We conclude that for recurrent mutations in the FGFR3 gene, that the HRM technique can be used as a faster, reliable and less expensive genotyping routine for the diagnosis of these pathologies than Sanger sequencing.

5-Aza-2'-deoxycytidine induces a greater inflammatory change, at the molecular levels, in normoxic than hypoxic tumor microenvironment.

Hypoxia is associated with tumor aggressiveness and poor prognosis, including breast cancer. Low oxygen levels induces global genomic hypomethylation and hypermethylation of specific loci in tumor cells. DNA methylation is a reversible epigenetic modification, usually associated with gene silencing, contributing to carcinogenesis and tumor progression. Since the effects of DNA methyltransferase inhibitor are context-dependent and as there is little data comparing their molecular effects in normoxic and hypoxic microenvironments in breast cancer, this study aimed to understand the gene expression profiles and molecular effects in response to treatment with DNA methyltransferase inhibitor in normoxia and hypoxia, using the breast cancer model. For this, a cDNA microarray was used to analyze the changes in the transcriptome upon treatment with DNA methyltransferase inhibitor (5-Aza-2'-deoxycytidine: 5-Aza-2'-dC), in normoxia and hypoxia. Furthermore, immunocytochemistry was performed to investigate the effect of 5-Aza-2'-dC on NF-κB/p65 inflammation regulator subcellular localization and expression, in normoxia and hypoxia conditions. We observed that proinflammatory pathways were upregulated by treatment with 5-Aza-2'-dC, in both conditions. However, treatment with 5-Aza-2'-dC in normoxia showed a greater amount of overexpressed proinflammatory pathways than 5-Aza-2'-dC in hypoxia. In this sense, we observed that the NF-κB expression increased only upon 5-Aza-2'-dC in normoxia. Moreover, nuclear staining for NF-κB and NF-κB target genes upregulation, IL1A and IL1B, were also observed after 5-Aza-2'-dC in normoxia. Our results suggest that 5-Aza-2'-dC induces a greater inflammatory change, at the molecular levels, in normoxic than hypoxic tumor microenvironment. These data may support further studies and expand the understanding of the DNA methyltransferase inhibitor effects in different tumor contexts.

The tumor suppressor role of salvador family WW domain-containing protein 1 (SAV1): one of the key pieces of the tumor puzzle.

PURPOSE: In the complex tumor scenario, understanding the function of proteins with protumor or antitumor roles is essential to support advances in the cancer clinical area. Among them, the salvador family WW domain-containing protein 1 (SAV1) is highlighted. This protein plays a fundamental role in the tumor suppressor face of the Hippo pathway, which are responsible for controlling cell proliferation, organ size, development and tissue homeostasis. However, the functional dysregulation of this pathway may contribute to tumorigenesis and tumor progression. As SAV1 is a tumor suppressor scaffold protein, we explored the functions performed by SAV1 with its partners, the regulation of its expression, and its antitumor role in various types of cancer. METHODS: We selected and analyzed 80 original articles and reviews from Pubmed that focuses on the study of SAV1 in cancer. RESULTS: SAV1 interacts with several proteins, has different functions and acts as tumor suppressor by other mechanisms besides Hippo pathway. SAV1 expression regulation seems to occur by microRNAs and rarely by mutation or promoter methylation. It is downregulated in different types of cancer, which leads to cancer promotion and progression and is associated with poor prognosis. In vivo models have shown that the loss of SAV1 contributes to tumorigenesis. CONCLUSION: SAV1 plays a relevant role as tumor suppressor in several types of cancer, highlighting SAV1 and the Hippo pathway's importance to cancer. Thus, encouraging further studies to include the SAV1 as a molecular key piece in cancer biology and in clinical approaches to cancer.

Effect of low power lasers on prokaryotic and eukaryotic cells under different stress condition: a review of the literature.

Radiations emitted by low power radiation sources have been applied for therapeutic proposals due to their capacity of inactivating bacteria and cancer cells in photodynamic therapy and stimulating tissue cells in photobiomodulation. Exposure to these radiations could increase cell proliferation in bacterial cultures under stressful conditions. Cells in infected or not infected tissue injuries are also under stressful conditions and photobiomodulation-induced regenerative effect on tissue injuries could be related to effects on stressed cells. The understanding of the effects on cells under stressful conditions could render therapies based on photobiomodulation more efficient as well as expand them. Thus, the objective of this review was to update the studies reporting photobiomodulation on prokaryotic and eukaryotic cells under stress conditions. Exposure to radiations emitted by low power radiation sources could induce adaptive responses enabling cells to survive in stressful conditions, such as those experienced by bacteria in their host and by eukaryotic cells in injured tissues. Adaptive responses could be the basis for clinical photobiomodulation applications, either considering their contraindication for treatment of infected injuries or indication for treatment of injuries, inflammatory process resolution, or tissue regeneration.

IL-17 Triggers Invasive and Migratory Properties in Human MSCs, while IFNy Favors their Immunosuppressive Capabilities: Implications for the "Licensing" Process.

Mesenchymal stromal cells (MSCs) were first used as a source for cell therapy in 1995; however, despite their versatility and unambiguous demonstration of efficacy and safety in preclinical/phase I studies, the positive effect of MSCs in human phase III studies did not resemble the success obtained in mouse models of disease. This dissonance highlights the need to more thoroughly study the immunobiology of MSCs to make better use of these cells. Thus, we aimed to study the immunobiology of MSCs by using chip array analysis as a method for general screening to obtain a global picture in our model study and found IFNy and IL-17 signaling as the first two "top canonical pathways" involved in MSCs immunomodulation. The role of IFNy in triggering the immunosuppressive properties of MSCs is well recognized by many groups; however, the role of IL-17 in this process remains uncertain. Interestingly, in contrast to IFNy, which actively improved the MSCs-mediated immunosuppression, IL-17 did not improve directly the MSCs-mediated immunosuppression. Instead, IL-17 signaling induced the migration of MSCs and inflammatory cells, bringing these cell types together and increasing the likelihood of the lymphocytes sensing the immunosuppressive molecules produced by the MSCs. These effects also correlated with high levels of cytokine/chemokine production and metalloprotease activation by MSCs. Importantly, this treatment maintained the MSCs safety profile by not inducing the expression of molecules related to antigen presentation. In this way, our findings highlight the possibility of using IL-17, in combination with IFNy, to prime MSCs for cell therapy to improve their biological properties and thus their therapeutic efficacy. Finally, the use of preactivated MSCs may also minimize variations among MSCs to produce more uniform therapeutic products. In the not-so-distant future, we envisage a portfolio of MSCs activated by different cocktails specifically designed to target and treat specific diseases. Graphical abstract.

Photobiomodulation by dual-wavelength low-power laser effects on infected pressure ulcers.

The aim of this study was to evaluate the effects of photobiomodulation (PBM) by dual-wavelength low-power lasers on the healing and bacterial bioburden of pressure ulcer (PU) models. Twenty-five male Swiss mice were divided into five equal groups. Ischemia reperfusion cycles were employed to cause PU formation by the external application of magnetic plates. Immediately after wounding, a suspension of Pantoea agglomerans was applied at the base of all the wounds of the infected groups, using a calibrated pipette. PBM (simultaneous emission at 660 and 808 nm, 142.8 J/cm2, in continuous wave emission mode) was applied to the PUs for 14 sessions. The animals were euthanized 14 days after PU induction, and their tissues were analyzed for wound contraction and reepithelialization, epidermis thickness, bacterial survival, and IL-1ß and IL-10 mRNA level evaluations. The PU areas appeared larger in the mice from the infected groups than in those in the laser group 4 days after PU induction and presented incomplete reepithelialization 14 days after PU induction. However, the PBM accelerated the wound healing in the infected + laser group compared with the infected group 11 and 14 days following the PU induction. The infected and irradiated PUs exhibited a thinner neo-epidermis than those in the infected group, and the bacterial survival decreased in the laser group; the relative expression IL-1ß mRNA levels demonstrated an increasing tendency while the relative expression IL-10 mRNA levels demonstrated a decreasing tendency in the infected + laser and laser groups. These results suggest that PBM improves healing by killing or inhibiting bacteria in PUs as well as by accelerating the wound healing, resulting in tissue repair.