Search

Androgenetic alopecia (AGA) is a prevalent hair loss disorder and influenced by genetic, hormonal, and environmental factors. Minoxidil and finasteride have been widely used for treating AGA. However, the side effects associated with these drugs often lead to poor patient compliance. In contrast, photobiomodulation (PBM), due to its safety and non-invasiveness, holds promising prospects for use. Although the promoting effects of PBM on AGA have been reported, the mechanisms by which PBM affects dermal papilla cells (DPCs) remain largely unknown. Hence, this study explored the impacts of both continuous wave (CW) and pulsed wave (PW) PBM on DPCs, and revealed the underlying actions of light parameters in PBM. Orthogonal experiments were conducted to evaluate the effects of CW PBM on DPCs at varying irradiances and doses, indicating that irradiance was the crucial parameter, as well as cell viability and proliferation were maximized at 8 mW/cm 2 and 8 J/cm 2 . For PW PBM, response surface methodology was employed to determine the influences of duty cycles, frequencies, and doses. The findings highlighted frequency as a primary factor, with the optimum cell viability observed at peak irradiance 10 mW/cm 2 , duty cycle 80 %, 500 Hz, and 8.8 J/cm 2 . Notably, PBM could enhance cell viability, proliferation, and migration in DPCs by activating the Wnt/β-Catenin signaling and suppressing Transforming Growth Factor signaling, particularly when applied in pulsed mode. Overall, this study determined the key light parameters that influence PBM effectiveness, further identified the optimal light conditions, and preliminary revealed into the mechanisms of PBM in DPCs, highlighting that PW PBM may be a competitive therapeutic option for alleviating AGA in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Photodynamic Therapy (PDT) is a therapeutic modality that combines the application of a photoactive compound (photosensitizer, PS) with low-power light to generate reactive oxygen species in the target tissue, resulting in cytotoxic damage and cell death, while sparing adjacent tissues. The objective of this study was to evaluate the phototoxicity of a cyanine dye with two chromophores (biscyanines, BCD) in systems with varying levels of cellular organization, and we used the Photogem® (a photosensitizer approved by the Brazilian ANVISA agency for clinical use in Photodynamic Therapy) as a positive control., Materials and Methods: The cytotoxicity of the compounds was assessed in vitro in 2D monolayers, 3D spheroid cultures, and artificial skin models. Four tumoral cell lines A375 (melanoma), HCB-541 (cutaneous squamous cell carcinoma), Vu120T and Vu147T (head and neck cancer), and two normal cell lines fibroblastic HFF-1 and keratinocyte HACAT were used in this study. Cell viability, migration, production of reactive oxygen species, expression of proteins linked to DNA damage and repair, internalization, and skin permeation of PS agents., Results: Light irradiation in the presence of the PS resulted in greater cytotoxic effects for BCD as compared to Photogem®, which was accompanied by an increase in the production of reactive oxygen species including H 2 O 2 , elevated levels of cleaved PARP, and a higher rate of phosphorylated H2AX protein. BCD demonstrated enhanced internalization and bioaccumulation in the spheroids and equivalent skin models., Conclusion: BCD, as a photosensitizer, showed higher cytotoxicity, with an increased ability to generate reactive oxygen species. This led to reduced cell viability, inhibited migration, and upregulated DNA damage-related proteins. Additionally, its enhanced cellular uptake improved skin barrier permeability, making BCD a strong candidate for in vivo Photodynamic Therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: Sonodynamic therapy (SDT) is an innovative, non-invasive approach to cancer treatment, by using low-intensity ultrasound to trigger the activation of sonosensitizers localized within cancerous cells. This current study aimed to explore the therapeutic efficacy of a new sonosensitizer, Sinoporphyrin Sodium (DVDMS), under ultrasound irradiation, against oral squamous cell carcinoma (OSCC)-derived SCC-154 cells, both in vitro and in vivo., Methods: Fluorescence spectra, cytotoxicity assessments, uptake mechanisms, and subcellular distributions of DVDMS within the SCC-154 cell line were detected. Additionally, the study comprehensively assessed the antitumor effect, oxidative stress responses, apoptosis, apoptosis-related proteins, autophagic processes, and ultrastructural changes in SCC-154 cells, both in vitro and in vivo, subsequent to treatment with low-intensity ultrasound (at 1.0 MHz, 1 W/cm 2 in vitro and 3 W/cm 2 in vivo) in conjunction with DVDMS also being examined., Results: The findings indicate that SCC-154 cells exhibit heightened sensitivity to DVDMS compared to SAS and HSC-3 cell lines. Within SCC-154 cells, DVDMS primarily localizes within the mitochondria and lysosomes. DVDMS-based SDT significantly increased the intracellular levels of reactive oxygen species (ROS), induced morphological changes such as mitochondrial swelling and formation of autolysosomes, and exhibited a notable dose-dependent reduction in cell viability in vitro. Also, DVDMS-SDT demonstrated significant inhibition of xenograft growth without discernible adverse effects. Mechanistically, DVDMS-SDT upregulated Bax expression while downregulating Bcl-2 expression, which led to the Bax/Bcl-2 ratio and induced autophagy., Conclusion: DVDMS-SDT triggers mitochondrial-dependent apoptosis in SCC-154 cells, unlike 5-ALA and protoporphyrin IX (PpIX). Also, the combination of DVDMS with ultrasound stimulation induces autophagy, with the onset of autophagic processes preceding apoptosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Exposure to artificial blue light, one of the most energetic forms of visible light, can increase oxidative stress in retinal cells, potentially enhancing the risk of macular degeneration. Retinal pigment epithelial (RPE) cells play a crucial role in this process; the loss of RPE cells is the primary pathway through which retinal degeneration occurs. In RPE cells, Kelch-like ECH-associated protein 1 (KEAP1) is located in both the nucleus and cytosol, where it binds to nuclear factor erythroid 2-related factor 2 (NRF2) and p62 (sequestosome-1), respectively. Blue light exposure activates the NRF2-heme oxygenase 1 (HMOX1) axis through both canonical and noncanonical p62 pathways thereby reducing oxidative damage, and initiates autophagy, which helps remove damaged proteins. These protective responses may support the survival of RPE cells. However, extended exposure to blue light drastically decreases the viability of RPE cells. This exposure diminishes the ability of KEAP1 to bind to p62 and reduces the level of KEAP1. Inhibition of autophagy does not prevent KEAP1 degradation, the NRF2-HMOX1 axis, or blue-light-induced cytotoxicity. However, proteasome inhibitor along with a transient increase in the amount of KEAP1 in RPE cells, partially restores the p62-KEAP1 complex and reduces blue-light-induced cytotoxicity. In vivo studies confirmed the downregulation of KEAP1 in damaged RPE cells. Mice subjected to periodic blue light exposure exhibited significant atrophy in the outer retina, particularly in the peripheral areas. Additionally, there was a significant decrease in c-wave electroretinography and pupillary light reflex, indicating functional impairments in both visual and nonvisual physiological processes. These data underscore the essential role of KEAP1 in managing oxidative defense and autophagy pathways triggered by blue light exposure in RPE cells., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To increase the therapeutic efficacy of nanoparticle (NP)-assisted photothermal therapy (PTT) and allow for a transition toward the clinical setting, it is pivotal to characterize the thermal effect induced in cancer cells and correlate it with the cell biological response, namely cell viability and cell death pathways. This study quantitatively evaluated the effects of gold nanorod (GNR)-assisted near-infrared (NIR) PTT on two different cancer cell lines, the 4T1 triple-negative breast cancer cells and the Pan02 pancreatic cancer cells. The interaction between nanomaterials and biological matrices was investigated in terms of GNR internalization and effect on cell viability at different GNR concentrations. GNR-mediated PTT was executed on both cell lines, at the same treatment settings to allow a straightforward comparison, and real-time monitored through thermographic imaging. A thermal analysis based on various parameters (i.e., maximum absolute temperature, maximum temperature change, temperature variation profile, area under the time-temperature change curve, effective thermal enhancement (ETE), and time constants) was performed to evaluate the treatment thermal outcome. While GNR treatment and NIR laser irradiation alone did not cause cell toxicity in the selected settings, their combination induced a significant reduction of cell viability in both cell lines. At the optimal experimental condition (i.e., 6 μg/mL of GNRs and 4.5 W/cm 2 laser power density), GNR-assisted PTT reduced the cell viability of 4T1 and Pan02 cells by 94% and 87% and it was associated with maximum temperature changes of 25 °C and 29 °C (i.e., ∼1.8-fold increase compared to the laser-only condition), maximum absolute temperatures of 55 °C and 54 °C, and ETE values of 78% and 81%, for 4T1 and Pan02 cells, correspondingly. Also, the increase in the GNR concentration led to a decrease in the time constants, denoting faster heating kinetics upon irradiation. Furthermore, the thermal analysis parameters were correlated with the extent of cell death. Twelve hours after NIR exposure, GNR-assisted PTT was found to mainly trigger secondary apoptosis in both cell lines. The proposed study provides relevant insights into the relationship between temperature history and biological responses in the context of PTT. The findings contribute to the development of a universal methodology for evaluating thermal sensitivity upon NP-assisted PTT on different cell types and lay the groundwork for future translational studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Alzheimer's disease, a prevalent neurodegenerative condition primarily affecting older adults, remains incurable. Its principle pathological hallmark is the accelerated accumulation of amyloid β (Aβ) protein. This study investigates the potential of photobiomodulation using near infrared light to counteract Aβ 1-42 -induced synaptic degeneration and neurotoxicity. We focused on the effect of 808 nm near-infrared laser diode (LD) on Aβ 1-42 cytotoxicity in primary cultured cortical neurons. We assessed cell survival using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, observing substantial benefits from LD irradiation with a power of 10 mW and a dose of 30 J. Cells exposed to Aβ 1-42 exhibited morphological changes indicative of synaptic damage and a significant decrease in the number of postsynaptic density protein-95 (PSD-95) contacts, which were significantly improved with near-infrared LD therapy. Furthermore, this therapy reduced Aβ and phosphorylated tau (P-tau) protein accumulation. Additionally, near-infrared LD irradiation substantially lessened the Aβ 1-42 -induced rise in glial fibrillary acid protein (GFAP) and ionized calcium-binding adaptor molecule 1 (IBA1) in astrocytes and microglia. Remarkably, near-infrared LD irradiation effectively inhibited phosphorylation of key proteins involved in Aβ 1-42 -induced necroptosis, namely Receptor-interacting protein kinase-3 (RIP3) and Mixed Lineage Kinase domain-Like protein (MLKL). Our findings suggest that near-infrared LD treatment significantly reduces neurodegeneration by reducing glial overactivation and neuronal necroptosis triggered by Aβ 1-42 . Thus, near-infrared LD treatment emerges as a promising approach for slowing or treating Alzheimer's disease, offering new avenues in its management., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

To investigate the potential of blue light photobiomodulation (PBM) in inducing ferroptosis, a novel form of regulated cell death, in OS cells, considering its known effectiveness in various cancer models. In this investigation, we exposed human OS cell lines, HOS and MG63, to different wavelengths (420, 460 and 480 nm) of blue light at varying irradiances, and examined cellular responses such as viability, apoptosis, levels of reactive oxygen species (ROS), and mitochondrial membrane potential (MMP). Transcriptome sequencing was employed to unravel the molecular mechanisms underlying blue light-induced effects, with validation via quantitative real-time PCR (qRT-PCR). Our findings revealed a wavelength- and time-dependent decrease in cell viability, accompanied by increased apoptosis and oxidative stress. Transcriptomic analysis identified differential expression of genes associated with ferroptosis, oxidative stress, and iron metabolism, further validated by qRT-PCR. These results implicated ferroptosis as a significant mechanism in the blue light-induced death of OS cells, potentially mediated by ROS generation and disruption of iron homeostasis. Also, An incomplete stress response was observed in MG63 cells induced by blue light exposure. Hence, blue light PBM holds promise as a therapeutic approach in OS clinical investigations; however, additional exploration of its underlying mechanisms remains imperative., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Ischemic heart disease is one of the most harmful conditions to cellular structure and function. After reperfusion treatment, a spectrum of adverse effects becomes evident, encompassing altered cell viability, heightened oxidative stress, activated autophagy, and increased apoptosis. Photobiomodulation (PBM) has been utilized in experimental models of cardiac hypoxia to enhance mitochondrial response and ameliorate biochemical changes in injured tissue. However, the effects of PBM on cultured cardiomyocytes subjected to hypoxia/reoxygenation are not yet well established., Method: H9C2 cardiomyocytes were exposed to hypoxia with concentrations of 300 μM CoCl 2 for 24 h, followed by 16 h of reoxygenation through incubation in a normoxic medium. Treatment was conducted using GaAIAs Laser (850 nm) after hypoxia at an intensity of 1 J/cm 2 . Cells were divided into three groups: Group CT (cells maintained under normoxic conditions), Group HR (cells maintained in hypoxia and reoxygenation conditions without treatment), Group HR + PBM (cells maintained in hypoxia and reoxygenation conditions that underwent PBM treatment). Cell viability was analyzed using MTT, and protein expression was assessed by western blot. One-way ANOVA with the Tukey post hoc test was used for data analysis. Differences were significant when p < 0.05., Results: PBM at an intensity of 1 J/cm 2 mitigated the alterations in cell survival caused by hypoxia/reoxygenation. Additionally, it significantly increased the expression of proteins Nrf2, HSP70, mTOR, LC3II, LC3II/I, and Caspase-9, while reducing the expression of PGC-1α, SOD2, xanthine oxidase, Beclin-1, LC3I, and Bax., Conclusion: PBM at intensities of 1 J/cm 2 reverses the changes related to oxidative stress, mitochondrial biogenesis, autophagy, and apoptosis caused by hypoxia and reoxygenation in a culture of cardiomyocytes., Competing Interests: Declaration of competing interest The authors declare that no conflict of interest is relevant to the content of this article., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The cytotoxic of α-Ag 2 WO 4 synthesized in different morphologies (cuboidal (AW-C), hexagonal rod-like (AW-HRL) and nanometric rod-like (AW-NRL) was analyzed to understand the impact of morphological modulation on the toxicity of 3 T3 cell lines in the dark and when photoactivated by visible light. Pathways of toxicity were examined, such as parameters and electrostatic interaction, uptake, ion release and ROS production. Cytotoxicity was observed for all samples after reaching concentrations exceeding 7.8 μg/mL. Uptake tests demonstrated that the samples were not internalized by cells, likely due to their negative surface charge. AW-NRL exhibited autophagy in the absence of light and during photoactivation, primarily attributed to its ability to generate singlet oxygen. Analyzing intercellular ROS and RNS production, AW-HRL induced an increase in NO through exposure to photo-generated hydroxyl radicals, while AW-NRL showed increases only at non-photoactivated concentrations and AW-C did not exhibit increases. Interestingly, in the dark, these cells showed a low propensity for apoptosis, with late apoptosis and necrosis being more pronounced. When photoactivated, this behavior changed, revealing predominantly apoptotic and late apoptotic cell death. There is a need for an understanding of how morphology can alter the biological properties of α-Ag 2 WO 4 to predict and optimize its effects on cellular responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The therapeutic potential of blue light photobiomodulation in cancer treatment, particularly in inhibiting cell proliferation and promoting cell death, has attracted significant interest. Oral squamous cell carcinoma (OSCC) is a prevalent form of oral cancer, necessitating innovative treatment approaches to improve patient outcomes. In this study, we investigated the effects of 420 nm blue LED light on OSCC and explored the underlying mechanisms. Our results demonstrated that 420 nm blue light effectively reduced OSCC cell viability and migration, and induced G2/M arrest. Moreover, we observed that 420 nm blue light triggered endoplasmic reticulum (ER) stress and mitochondrial dysfunction in OSCC cells, leading to activation of the CHOP signal pathway and alterations in the levels of Bcl-2 and Bax proteins, ultimately promoting cell apoptosis. Additionally, blue light suppressed mitochondrial gene expression, likely due to its damage to mitochondrial DNA. This study highlights the distinct impact of 420 nm blue light on OSCC cells, providing valuable insights into its potential application as a clinical treatment for oral cancer., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Photobiomodulation (PBM) is a well-established medical technology that employs diverse light sources like lasers or light-emitting diodes to generate diverse photochemical and photophysical reactions in cells, thereby producing beneficial clinical outcomes. In this study, we introduced an 830 nm near-infrared (NIR) laser irradiation system combined with a microscope objective to precisely and controllably investigate the impact of PBM on the migration and viability of human adipose mesenchymal stem cells (hADSCs). We observed a biphasic dose-response in hADSCs' viability and migration after PBM exposure (0-10 J/cm 2 ), with the 5 J/cm 2 group showing significantly higher cell viability and migration ability than other groups. Additionally, at the optimal dose of 5 J/cm 2 , we used nanoparticle tracking analysis (NTA) and found a 6.25-fold increase in the concentration of extracellular vesicles (EVs) derived from hADSCs (PBM/ADSC-EVs) compared to untreated cells (ADSC-EVs). Both PBM/ADSC-EVs and ADSC-EVs remained the same size, with an average diameter of 56 nm measured by the ExoView R200 system, which falls within the typical size range for exosomes. These findings demonstrate that PBM not only improves the viability and migration of hADSCs but also significantly increases the EV yield., Competing Interests: Declaration of Competing Interest It was declared that no conflicts of interest exist about the publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As the outermost layer of the human body, the skin suffers from various external factors especially light damage, among which ultraviolet B (UVB) irradiation is common and possesses a relatively high biological damage capacity. Pyroptosis is a newly discovered type of programmed cell death, which can induce cell rupture and induce local inflammatory response. However, the molecular mechanisms of pyroptosis in photodamaged skin is poorly understood. Baicalin, a flavonoid extracted from the desiccated root of Scutellaria baicalensis Georgi (Huang Qin). Despite its antioxidant abilities, whether baicalin protects skin by attenuating UVB-induced pyroptosis remains unclear, which was the aim of this study. The UVB-induced acute skin damage model was established by using human immortalized keratinocytes (HaCaT cells) and Kunming (KM) strain mice. The protective dose selection for baicalin is 50 μM in vitro and 100 mg/kg in vivo. In in vitro study, UVB irradiation significantly decreased cell viability, increased cell death and oxidative stress in HaCaT cells, while pretreatment with baicalin improved these phenomena. Furthermore, the baicalin pretreatment notably suppressed nuclear factor kappa B (NF-κB) translocation, the NLRP3 inflammasome activation and gasdermin D (GSDMD) maturation, thus effectively attenuating UVB-induced pyroptosis. In in vivo study, the baicalin pretreatment mitigated epidermal hyperplasia, collagen fiber fragmentation, oxidative stress and pyroptosis in UVB-irradiated mouse skin. In a nutshell, this study suggests that baicalin could be a potential protective agent to attenuate acute skin damage induced by UVB irradiation through decreasing oxidative stress and suppressing NF-κB/NLRP3/GSDMD-involved pyroptosis., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

In recent decades, the laser treatment of cancer has been introduced as a promising treatment option. Because of the maldistribution of optical energy and an ambiguous boundary between the normal and tumor tissues, laser irradiation can stimulate residual cancer cells, leading to a cancer regrowth. As photobiomodulation (PBM) is involved in an extensive range of cellular responses, profound comprehension of photo-stimulated mechanisms against the cancer cells is required to establish a safety margin for PBM. Therefore, we aimed to identify the stimulant effects of PBM at various wavelengths against the tumor cells to establish a safety margin for the laser treatment. CT26 murine colon cancer cells were exposed to either 405 (BL), 635 (VIS), or 808 (NIR) nm laser lights at the fluences of 0, 10, 30, and 50 J/cm 2 . In addition, CT26 tumor-bearing mice were irradiated with BL, VIS, or NIR at a fluence of 30 J/cm 2 . Both the proliferation and angiogenesis potential of the CT26 cells and tumors were evaluated using the MTT assay, western blot, and immunohistochemistry (IHC) staining analyses. Although cell viability was not statistically significant, BL significantly induced p-ERK upregulation in the CT26 cells, indicating that PBM with BL can stimulate proliferation. In vivo tests showed that the NIR group exhibited the maximum relative tumor volume, and BL yielded a slight increase compared to the control. In the IHC staining and western blot analyses, both BL and NIR increased the expression of EGFR, VEGF, MMP-9, and HIF-1α, which are related to the proliferation and angiogenesis-related factors. Further investigations will be pursued to clarify the molecular pathways that depend on the cancer cell types and laser wavelengths for the establishment of safety guidelines in clinical environments., Competing Interests: Declaration of Competing Interest The authors declare that have no conflicts of interest or financial relationships to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

The rise in the antibiotic resistance rate of Helicobacter pylori has led to an increasing eradication failure of this carcinogenic bacterial pathogen worldwide. This underlines the need for alternative antibacterial strategies against H. pylori infection. Antimicrobial photodynamic therapy (aPDT) is a promising non-pharmacological antibacterial technology. In this study, the selective killing activities of three benzylidene cyclopentanone (BCP) photosensitizers (Y1, P1 and P3) towards H. pylori over normal human gastric epithelial GES-1 cells were evaluated and the ex vivo photodynamic inactivation effect was preliminarily assessed on twelve H. Pylor-infected mice. Results showed that under the irradiation of 24 J/cm 2 532 nm laser, Y1, P1 and P3 at 2.5 μM induced a 3-log 10 reduction of H. pylori CFU (99.9% killing). Confocal images showed that P3, unlike Y1 and P1, could not be uptaken by GES-1 cells. P3 at 2.5 to 20 μM showed not significant (p > 0.05) phototoxicity to GES-1 cells, nevertheless, Y1 and P1 under the same concentrations exhibited remarkable phototoxicity to GES-1 cells. In the co-culture of H. pylori and GES-1 cells, P3 at 2.5 μM led to a complete eradication of H. pylori under the irradiation of 24 J/cm 2 532 nm laser. While for the GES-1 cells, no significant (p > 0.05) phototoxicity was observed under the same aPDT dosage. The ex vivo experiments showed that P3 mediated aPDT resulted in 82.4% to 100% reduction of H. pylori CFU without damaging the gastric mucosa. To sum up, P3 is a promising anti-H. pylori photosensitizer with the ability to selectively photo-inactivate H. pylori while sparing normal gastric tissues., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this paper, the photodynamic effect of a ternary nanocomposite (TiO 2 -Ag/graphene) on Escherichia coli bacteria and two human cell lines: A375 (melanoma) and HaCaT (keratinocyte) after exposure to different wavelength domains (blue, green or red-Light Emitting Diode, LED) was analyzed. The results obtained through bioassays were correlated with the morphological, structural and spectral data obtained through FT-IR, XPS and UV-Vis spectroscopy, powder X-Ray diffractometry (XRD) and STEM/EDX techniques, leading to conclusions that showed different photodynamic activation mechanisms and effects on bacteria and human cells, depending on the wavelength. The nanocomposite proved a therapeutic potential for blue light-activated antibacterial treatment and revealed a keratinocyte cytotoxic effect under blue and green LEDs. The red light-nanocomposite duo gave a metabolic boost to normal keratinocytes and induced stasis to melanoma cells. The light and nanocomposite combination could be a potential therapy for bacterial keratosis or for skin tumors., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Photobiomodulation (PBM) is a promising medical treatment modality in the area of photodynamic therapy (PDT). In this study, we investigated the effect of combined therapy in a 3D microenvironment using aluminum chloride phthalocyanines (AlClPc) as the photosensitizing agent. Normal human fibroblast-containing collagen biomatrix was prepared and treated with an oil-in-water (o/a) AlClPc-loaded nanoemulsion (from 0.5 to 3.0 μM) and irradiated at a range of fluences (from 0.1 to 3.0 J/cm 2 ) using a continuous-wave light-emitting diode (LED) irradiation system (660 nm). PBM at 1.2 J/cm 2 and AlClPc/NE at 0.5 μM modified the fibroblast signaling response under 3D conditions, promoting collagen synthesis, ROS production, MMP-9 secretion, proliferation of the actin network, and facile myofibroblastic differentiation. PBM alone (at 1.2 J/cm 2 and 0.3 J/cm 2 ) had no significant effect on any of these parameters. The combined therapy affected myofibroblastic differentiation, inflammatory response, and extracellular matrix pliability, and should thus be examined further in subsequent studies considering that no side effects of PBM have been reported. Even though significant progress has been made in the field of phototherapy in recent years, it is necessary to further elucidate the detailed mechanisms underlying its effects already shown in 2D conditions to increase the acceptance of this beneficial and non-invasive therapeutic approach., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Photodynamic therapy (PDT) is an approved therapeutic approach and an alternative to conventional chemotherapy for the treatment of several types of cancer with the advantages of reducing the side effects and developing resistance mechanisms. Here, was evaluated the photosensitization capabilities of 5,10,15,20-tetrakis[4-(pyridinium-1-yl-methyl)phenyl]porphyrin (3), its N-confused isomer (4) and of the neutral precursors (1) and (2) and the results were compared with the ones obtained with the cationic 5,10,15,20-tetrakis(1-methylpyridinium-4-yl)porphyrin (TMPyP). Both regular porphyrin derivatives 1 and 3 showed higher efficiency to generate singlet oxygen than TMPyP. The PDT assays towards MCF-7 cells under red light irradiation (λ > 640 nm, 23.7 mW cm -2 ) demonstrated that the cationic porphyrin 3 is an efficient photosensitizer to kill MCF-7 breast cancer cells. The study of the cell death mechanisms induced by the photodynamic process showed that the studied porphyrin 3 and TMPyP caused cell death by autophagic flux and necrosis., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Skin is the largest body organ and can be affected by several factors, such as ultraviolet (UV) radiation. UV radiation is subdivided in UVA, UVB and UVC according to the radiation wavelength. UVC radiation does not cross the ozone layer; UVB cause DNA damage and is closely related to carcinogenesis; UVA radiation penetrates deeply into the skin, reaching epidermis and dermis and is considered the main promoter of skin aging, known as photoaging. In order to understand photoaging mechanisms and propose efficient therapies, several photoaging study models have been developed, each with benefits and limitations, but most of them use very high doses of UVA radiation, which is not compatible with our daily sun exposure. The objective of this work was to develop a human ex vivo photoaging model induced by UVA exposure compatible to a summer in Brazil. For this, human skin fragments were obtained from healthy donors who underwent otoplasty surgery and skin explants were prepared and placed in plates, with the epidermis facing upwards. Skin explants were exposed to UVA at 16 J/cm 2 carried out by protocols of 2 or 4 exposures. Results showed an increase of oxidative damage, inflammatory cells, collagenolytic and elastolytic MMPs expression as well as a decrease of elastin expression, suggesting that the experimental model based on skin explants is able to evaluate UVA-induced aging in human skin., (Copyright © 2021 Elsevier B.V. All rights reserved.)

A need exists for further research elucidating the benefits of environmentally safe photoprotective agents against ultraviolet (UV) exposure, and plant extracts represent a human-friendly alternative formulation. This study was designed to evaluate the potential use of Bellis perennis extract (BPE), from the Asteraceae family, known as the common daisy or the English daisy, in cosmeceuticals as a photoprotective factor, using an in vitro model of UVA-induced keratinocyte damage. Human skin keratinocytes (HaCaT cell line) were incubated with BPE at 0.01, 0.1, or 1% in Dulbecco's Modified Eagle Medium (DMEM), and after 15 min they were submitted to UVA radiation at 5, 10, and 15 J/cm 2 doses, respectively. For comparative purposes, Polypodium leucotomos extract (PLE), known as the fern, was used as a positive control in assessing the photoprotective effect. After 24 h of UVA exposure, cell viability (MTT and LDH assays), levels of cleaved caspase-3, cyclooxygenase-2, IL-6, reactive oxygen species (ROS) and antioxidant enzyme (catalase, SOD, and glutathione peroxidase) activity were determined. UVA radiation at 5, 10, and 15 J/cm 2 doses reduced cell viability to 63%, 43%, and 23%, respectively; we selected 10 J/cm 2 for our purposes. After 24 h of UVA exposure, treatment with 1% BPE and 1% PLE significantly recovered cell viability (p < 0.05). Furthermore, treatment was associated with lower cleaved caspase-3 and ROS levels, higher catalase activity, and lower IL-6 levels in the treated UVA keratinocytes compared with the untreated UVA group (p < 0.01). Our results demonstrate photoprotective and immunomodulatory effects of BPE in skin keratinocytes and support its use as a bioactive agent in cosmetic formulations to prevent skin damage caused by exposure to the UV light., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The delta-amino acid 5-aminolevulinic acid (ALA), is the precursor of the endogenous photosensitiser Protoporphyrin IX (PpIX), and is currently approved for Photodynamic Therapy (PDT) of certain superficial cancers. However, ALA-PDT is not very effective in diseases in which T-cells play a significant role. Cutaneous T-cell lymphomas (CTCL) is a group of non-Hodgkin malignant diseases, which includes mycosis fungoides (MF) and Sézary syndrome (SS). In previous work, we have designed new ALA esters synthesised by three-component Passerini reactions, and some of them showed higher performance as compared to ALA. This work aimed to determine the efficacy as pro-photosensitisers of five new ALA esters of 2-hydroxy-N-arylacetamides (1f, 1 g, 1 h, 1i and 1 k) of higher lipophilicity than ALA in Myla cells of MF and HuT-78 cells of SS. We have also tested its effectiveness against ALA and the already marketed ALA methyl ester (Me-ALA) and ALA hexyl ester (He-ALA). Both cell Myla and SS cells were effectively and equally photoinactivated by ALA-PDT. Besides, the concentration of ALA required to induce half the maximal porphyrin synthesis was 209 μM for Myla and 169 μM for HuT-78 cells. As a criterion of efficacy, we calculated the concentration of the ALA derivatives necessary to induce half the plateau porphyrin values obtained from ALA. These values were achieved at concentrations 4 and 12 times lower compared to ALA, according to the derivative used. For He-ALA, concentrations were 24 to 25 times lower than required for ALA for inducing comparable porphyrin synthesis in both CTCL cells. The light doses for inducing 50% of cell death (LD50) for He-ALA, 1f, 1 g, 1 h and 1i were around 18 and 25 J/cm 2 for Myla and HuT-78 cells respectively, after exposure to 0.05 mM concentrations of the compounds. On the other hand, the LD50s for the compound 1 k were 40 and 57 J/cm 2 for Myla and HuT-78, respectively. In contrast, 0.05 mM of ALA and Me-ALA did not provoke photokilling since the concentration employed was far below the porphyrin saturation point for these compounds. Our results suggest the potential use of ALA derivatives for topical application in PDT treatment of MF and extracorporeal PDT for the depletion of activated T-cells in SS., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Nicotinamide adenine dinucleotide (NAD + ) is a crucial coenzyme in energy production. The imbalance of NAD + synthesis has been found to trigger age-related diseases, such as metabolic disorders, cancer, and neurodegenerative diseases. Also, UV irradiation induces NAD + depletion in the skin. In mammals, nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD + salvage pathway and essential for NAD + homeostasis. However, but few studies have focused on the role of NAMPT in response to UV irradiation. Here, we show that NAMPT prevents NAD + depletion in epidermal keratinocytes to protect against the mild-dose UVA and UVB (UVA/B)-induced proliferation defects. We showed that poly(ADP-ribose) polymerase (PARP) inhibitor rescued the NAD + depletion in UVA/B-irradiated human keratinocytes, confirming that PAPR transiently exhausts cellular NAD + to repair DNA damage. Notably, the treatment with a NAMPT inhibitor exacerbated the UVA/B-induced loss of energy production and cell viability. Moreover, the NAMPT inhibitor abrogated the sirtuin-1 (SIRT1)-mediated deacetylation of p53 and significantly inhibited the proliferation of UVA/B-irradiated cells, suggesting that the NAMPT-NAD + -SIRT1 axis regulates p53 functions upon UVA/B stress. The supplementation with NAD + intermediates, nicotinamide mononucleotide and nicotinamide riboside, rescued the UVA/B-induced phenotypes in the absence of NAMPT activity. Therefore, NAD + homeostasis is likely essential for the protection of keratinocytes from UV stress in mild doses. Since the skin is continuously exposed to UVA/B irradiation, understanding the protective role of NAMPT in UV stress will help prevent and treat skin photoaging., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Far-infrared (FIR) irradiation is reported to inhibit cell proliferation in various types of cancer cells; the underlying mechanism, however, remains unclear. We explored the molecular mechanisms using MDA-MB-231 human breast cancer cells. FIR irradiation significantly inhibited cell proliferation and colony formation compared to hyperthermal stimulus, with no alteration in cell viability. No increase in DNA fragmentation or phosphorylation of DNA damage kinases including ataxia-telangiectasia mutated kinase, ataxia telangiectasia and Rad3-related kinase, and DNA-dependent protein kinase indicated no DNA damage. FIR irradiation increased the phosphorylation of checkpoint kinase 2 (Chk2) at Thr68 (p-Chk2-Thr 68 ) but not that of checkpoint kinase 1 at Ser345. Increased nuclear p-Chk2-Thr 68 and Ca 2+ /CaM accumulations were found in FIR-irradiated cells, as observed in confocal microscopic analyses and cell fractionation assays. In silico analysis predicted that Chk2 possesses a Ca 2+ /calmodulin (CaM) binding motif ahead of its kinase domain. Indeed, Chk2 physically interacted with CaM in the presence of Ca 2+ , with their binding markedly pronounced in FIR-irradiated cells. Pre-treatment with a Ca 2+ chelator significantly reversed FIR irradiation-increased p-Chk2-Thr 68 expression. In addition, a CaM antagonist or small interfering RNA-mediated knockdown of the CaM gene expression significantly attenuated FIR irradiation-increased p-Chk2-Thr 68 expression. Finally, pre-treatment with a potent Chk2 inhibitor significantly reversed both FIR irradiation-stimulated p-Chk2-Thr 68 expression and irradiation-repressed cell proliferation. In conclusion, our results demonstrate that FIR irradiation inhibited breast cancer cell proliferation, independently of DNA damage, by activating the Ca 2+ /CaM/Chk2 signaling pathway in the nucleus. These results demonstrate a novel Chk2 activation mechanism that functions irrespective of DNA damage., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Photodynamic therapy (PDT) is a promising glioma therapy; however, its efficacy is compromised due to the PDT-induced reactive oxygen species (ROS) production being limited by the local hypoxic tumor microenvironment. Furthermore, Hypoxia activates sodium/hydrogen exchanger 1 (NHE1), an essential component for tumor progression and metastasis, enables glioma cells (GC) to escape PDT-mediated phototoxicity via increased H + extrusion. However, interactions between NHE1 expression with ROS level involving response of GC remain unclear. Dihydroartemisinin (DHA), a ROS generator, has extensive anti-tumor effects. This study aimed to explore whether PDT along with DHA could amplify the total ROS levels and diminish GC invasion and migration by inhibiting NHE1 expression. Proliferation and invasion of U251 and LN229 cells were evaluated under different treatments using cell counting Kit-8 (CCK-8), transwell, and wound healing assays. ROS levels were measured using fluorescence probes and flow cytometry. NHE1 levels were detected by immunofluorescence and western blotting. Co-treatment effects and molecular events were further confirmed in a bilateral tumor-bearing nude mouse model. PDT with synergistic DHA significantly increased the total abundance of ROS to further suppress the invasion and migration of GC by reducing NHE1 levels in vitro. Using a bilateral glioma xenograft mouse model with primary and recurrent gliomas, we found that PDT markedly suppressed primary tumor growth, while PDT in synergy with DHA also suppressed recurrent tumors, and improved overall survival by regulating the ROS-NHE1 axis. No evident side effects were observed. Our results suggest that PDT with DHA can amplify the total ROS levels to weaken GC invasion and migration by suppressing NHE1 expression in vitro and in vivo, thus abolishing the resistance of GC to PDT. The synergistic therapy of PDT and DHA therefore represents a more efficient and safe strategy for comprehensive glioma treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In this project, we studied the thermal and chemical method for the synthesis of carbon dots (CDs)/Hematite (α-Fe 2 O 3 ) quantum dots and the preparation of hydroxypropyl cellulose cross-linked chitosan (HPCCS) and ulvan (UN) was performed by chemical method. Carbon dots/α-Fe 2 O 3 quantum dots with size distribution of 3-5 nm were completely encapsulated in the HPCCS/UN NPs to obtain composites, which indicated unique characteristics with respect to antimicrobial, pH-responsive and optical properties. The CDs-HQDs/HPCCS/UN nanocomposites exhibited a single-excitation (440 nm), dual-emission fluorescence property (505 nm and 628 nm for green and red light from CDs-HQDs and HPCCS/UN NPs). The nanocomposites played as a pH-responsive drug delivery process to release ulvan at a fast rate in pH 7.4 buffer solution but at a slow rate in low pH solutions. The CDs-HQDs/HPCCS/UN nanocomposites gained the highest photocatalytic activity for degrading 4-chlorophenol (4-CPh) as a pollutant (>98% during 70 min under sunlight irradiation). Moreover, the nanocomposites indicated great inhibitory influences towards bacterial and fungal., (Copyright © 2021. Published by Elsevier B.V.)

A combination of metabolic modifications by light stimulus and photodynamic action is very attractive. Photobiomodulation therapy (PBMT) comprehends a vast range of applications and has been shown to be suitable to ease morbidities caused by chemotherapy and radiation, such as mucositis and dermatitis. The current study investigates the effects of near-infrared PBMT combined with porphyrin-based photodynamic therapy (PDT) in squamous cell carcinoma cell lines SCC-25 and SCC-4. The aim is to evaluate the potential of this combination to improve PDT outcome by increasing cell toxicity. Many techniques were used to verify the combined effect. Photobiomodulation (PBM) enhanced PDT action in SCC-25 cells by increasing photosensitizer (PS) uptake and production of reactive oxygen species (ROS). The equivalent was not seen in SCC-4 cells compared to the PDT only group. We believe these effects are strongly related to the interval of application between PBMT, PS incubation and PDT. Additionally, the effect of ascorbic acid on preventing PBM effects in PDT shows that ROS play an important role in the early mechanisms of PBM-PDT. Therefore, we believe PBM-PDT combination is worth exploring, for its benefit-cost ratio and simple protocols, along with the possibility of improvement in treatment resuts., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dual phototherapy agents have attracted great interest in recent years as they offer enhanced cytotoxicity on cancer cells due to the synergistic effect of photodynamic and photothermal therapies (PDT/PTT). In this study, we demonstrate a brominated hemicyanine (HC-1), which is previously shown as mitochondria targeting PDT agent, can also serve as an effective photosensitizer for PTT for the first time under a single (640 nm or 808 nm) and dual laser (640 nm + 808 nm) irradiation. Generation of reactive oxygen species and photothermal conversion as a function of irradiation wavelength and power were studied. Both single wavelength irradiations caused significant phototoxicity in colon and cervical cancer cells after 5 min of irradiation. However, co-irradiation provided near-complete elimination of cancer cells due to synergistic action. This work introduces an easily accessible small molecule-based synergistic phototherapy agent, which holds a great promise towards the realization of local, rapid and highly efficient treatment modalities against cancer., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The expansion of optogenetics via the development and application of new opsins has opened a new world of possibilities as a research and therapeutic tool. Nevertheless, it has also raised questions about the innocuity of using light irradiation on tissues and cells such as those from the Peripheral Nervous System (PNS). Thus, to investigate the potential of PNS being affected by optogenetic light irradiation, rat dorsal root ganglion neurons and Schwann cells were isolated and their response to light irradiation examined in vitro. Light irradiation was delivered as millisecond pulses at wavelengths in the visible spectrum between 627 and 470 nm, with doses ranging between 4.5 and 18 J/cm 2 at an irradiance value of 1 mW/mm 2 . Results show that compared to cultures kept in dark conditions, light irradiation at 470 nm reduced neurite outgrowth in dissociated dorsal root neurons in a dose dependent manner while higher wavelengths had no effect on neuron morphology. Although neurite outgrowth was limited by light irradiation, no signs of cell death or apoptosis were found. On the other hand, peripheral glia, Schwann cells, were insensitive to light irradiation with metabolism, proliferation, and RNA levels of transcription factors c-Jun and krox-20 remaining unaltered following stimulation. As the fields of photostimulation and optogenetics expand, these results indicate the need for consideration to cell type response and stimulation parameters for applications in vitro and further investigation on specific mechanisms driving response., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Photobiomodulation (PBM) is reported to impart a range of clinical benefits, from the healing of chronic wounds to athletic performance enhancement. The increasing prevalence of this therapy conflicts with the lack of understanding concerning specific cellular mechanisms induced by PBM. Herein, we systematically explore the literature base, specifically related to PBM (within the range 600-1070 nm) and its influence on dermal fibroblasts. The existing research in this field is appraised through five areas: cellular proliferation and viability; cellular migration; ATP production and mitochondrial membrane potential; cellular protein expression and synthesis; and gene expression. This review demonstrates that when fibroblasts are irradiated in vitro within a set range of intensities, they exhibit a multitude of positive effects related to the wound healing process. However, the development of an optimal in vitro framework is paramount to improve the reliability and validity of research in this field., (Copyright © 2020 Elsevier B.V. All rights reserved.)

WLEDs have lately been the preferred lighting device based on properties such as energy saving, high efficiency, longevity, and environmental protection. However, studies on the safety of white light-emitting diode (WLED) are limited. In our previous study, we found that WLED light (4000 K ± 500 K color temperature, 250 lx, and 20 min exposure) is photocytotoxic to three mammalian cell lines by causing cell lipid peroxidation. To further investigate the potential photocytotoxicity of WLEDs on the human body, we used two human eye cell lines SRA01/04 and D407 as target cells for evaluating its potential phototoxicity on the human eye in the present study based on cell viability, apoptosis, and intracellular oxidative stress assays, as well as the activation levels of reactive oxygen species (ROS)-related apoptosis pathways, including extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK) and p38 kinase (p38), using mitogen-activated protein kinase (MAPK) signaling pathway assays. The results showed that WLED light has photocytotoxicities on SRA01/04 and D407 cells, which were both in a time-, irradiance-, and color temperature-dependent manner and strongest at the conditions of 2 h irradiation time, 60 W/m 2 irradiance, and 4000 K color temperature. Moreover, the photocytotoxicity of red light-emitting diode (LED) light was the strongest in the three tested monochromatic light compositions of WLED. Mechanism studies show that the potential phototoxicity of WLED on human lens epithelium and retinal pigment epithelium may be caused by its induced oxidative stress damage via the JNK and p38 MAPKs pathways., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Graphene, which is a unique 2D nanomaterials has received widespread attention for photothermal therapy (PTT) application. Here, we have designed the nanocomposite using polydopamine (PDA) functionalized reduced graphene oxide (rGO) nanosheets and bimetallic AuPd nanoparticles (NPs). The bimetallic AuPd nanoparticles decorated PDA functionalized rGO (AuPd-rGO/PDA) nanocomposite is synthesized by simple chemical reduction technique resulting in an average size of AuPd bimetallic nanostructure of 4.18 nm. The photothermal activity of the AuPd-rGO/PDA nanocomposite is explored under the irradiation of near infrared (NIR) laser sources of wavelength 915 nm. The temperature rises nearly 51 ± 3 °C within 3 min of irradiation NIR laser light resulting in the ablation of MDAMB-231 cancer cells up to concentration of 25 μg mL -1 of AuPd-rGO/PDA nanocomposite. This high performance of the ablation of cancer cells by photothermal therapy technique was facilitated using a low concentration of the nanocomposite by the synergistic effects of the bimetallic AuPd as well as rGO and PDA functionalization. The AuPd-rGO/PDA nanocomposite demonstrated the high biocompatibility towards normal healthy cell lines (L929) and exhibits survival efficiency of more than 85%. We also demonstrated the biocompatibility of the AuPd-rGO/PDA nanocomposite materials on the zebrafish embryos (Danio rerio). This work thus illustrates that the AuPd-rGO/PDA nanocomposite could behave as favourable nanoplatform for tumor therapeutics., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Impaired wound healing is a common complication of diabetes mellitus (DM) and the underlying mechanism of this impairment is still unclear. Fibroblast, as the main reconstructing cell, secretes some critical growth factors and cytokine contributing to wound healing. It is well known that DM alters the behavior of these cells and photobiomodulation therapy (PBMT) compensates some impairments in diabetic fibroblasts. Therefore, the aim of the present study was to demonstrate the impact of diabetes and the role of PBMT through low level laser irradiation on secretory profile of human diabetic fibroblasts. Primary human dermal fibroblasts from normal (HDFs) and diabetic (DHDFs) donors were harvested. For PBMT, the DHDFs were irradiated with a Helium-Neon laser at 632.8 nm wavelength and energy density of 0.5 J/cm 2 , as laser treated group (LT-DHDFs). Next, some cellular behaviors and secretory profiling array for 60 growth factors/cytokines were investigated in LT-DHDFs and then compared with those of controls. The data showed that the PBMT could compensate such impairments occurred in DHDFs in terms of viability, proliferation, and migration. Furthermore, considering our novel findings, out of those 20 growth factors/cytokines involved in cell proliferation, immune system regulation, and cell-cell communication pathways, which significantly decreased in DHDF as compared with HDFs, the PBMT could compensate seven in LT-DHDFs as compared with DHDFs. The seven growth factor/cytokines, which are mainly involved in cell-cell communication, positive regulation of cell proliferation, and chemokine mediated pathway included BDNF, Eotaxin-3, FGF6, FGF7, Fractalkine, fit-3ligand, and GCP-2. Therefore, it is suggested that scrutinizing these differentially secreted molecules and the impaired pathways in DHDFs, in combination with those compensated in LT-DHDFs, could raise our knowledge to manage diabetic ulcer through a feasible and cost effective intervention, specifically PBMT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The harmful effects of low energy UVA photons (315-400 nm) are associated with the massive production of reactive oxygen species resulting in oxidative stress. In response to oxidative damage, NF-E2-related factor 2 (Nrf2) is translocated to the nucleus and drives the expression of detoxication and antioxidant enzymes. UVA's effect on Nrf2 has been quite well characterised in dermal fibroblasts. However, there is a dearth of such information for keratinocytes. This study aimed to evaluate and compare the effect of UVA radiation on the Nrf2 pathway and oxidative stress related proteins in primary human dermal fibroblasts (NHDF), epidermal keratinocytes (NHEK) and human keratinocyte cell line HaCaT. NHDF were exposed to doses of 2.5-7.5 J/cm 2 , NHEK and HaCaT to 10-20 J/cm 2 using a solar simulator. Effects on Nrf2 translocation were evaluated after 1, 3 and 6 h and Nrf2-controlled proteins (heme oxygenase 1 (HO-1), NAD(P)H:quinone oxidoreductase 1 (NQO1), glutathione reductase (GSR), glutathione-S-transferase (GST), interleukine-6 (IL-6), and matrix metalloproteinases (MMP-1, MMP-2)) after 3, 6 and 24 h. The results showed the fastest Nrf2 translocation was in UVA-irradiated HaCaT (1 h), persisting until the subsequent time interval (3 h), while in primary keratinocytes the effect of radiation was minimal. In NHDF, UVA-stimulated Nrf2 translocation was conspicuous 3 h after UVA treatment. In NHDF, most of the studied proteins (NQO1, HO-1, GSR, GSTM1 and MMP-1) showed the highest level 24 h after UVA exposure, except for MMP-2 and IL-6 which had their highest level at a shorter time incubation interval (3 h). In NHEK, NQO1, HO-1 and GST were increased 6 h after UVA exposure, GSR and MMP-2 level was slightly below or above the control level, and MMP-1 and IL-6 increased at shorter time intervals. When comparing NHEK and HaCaT, these cells displayed contrary responses in most of the Nrf2-controlled proteins. Thus, primary keratinocytes cannot be replaced with HaCaT when studying cell signalling such as the Nrf2 driven pathway and Nrf2-controlled proteins., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Actin cytoskeleton remodeling is the major motor of cytoskeleton dynamics driving tumor cell adhesion, migration and invasion. The typical RhoA, RhoB and RhoC GTPases are the main regulators of actin cytoskeleton dynamics. The C3 exoenzyme transferase from Clostridium botulinum is a toxin that causes the specific ADP-ribosylation of Rho-like proteins, leading to its inactivation. Here, we examine what effects the Rho GTPase inhibition and the consequent actin cytoskeleton instability would have on the emergence of DNA damage and on the recovery of genomic stability of malignant melanoma cells, as well as on their survival. Therefore, the MeWo cell line, here assumed as a melanoma cell line model for the expression of genes involved in the regulation of the actin cytoskeleton, was transiently transfected with the C3 toxin and subsequently exposed to UV-radiation. Phalloidin staining of the stress fibers revealed that actin cytoskeleton integrity was strongly disrupted by the C3 toxin in association with reduced melanoma cells survival, and further enhanced the deleterious effects of UV light. MeWo cells with actin cytoskeleton previously perturbed by the C3 toxin still showed higher levels and accumulation of UV-damaged DNA (strand breaks and cyclobutane pyrimidine dimers, CPDs). The interplay between reduced cell survival and impaired DNA repair upon actin cytoskeleton disruption can be explained by constitutive ERK1/2 activation and an inefficient phosphorylation of DDR proteins (γH2AX, CHK1 and p53) caused by C3 toxin treatment. Altogether, these results support the general idea that actin network help to protect the genome of human cells from damage caused by UV light through unknown molecular mechanisms that tie the cytoskeleton to processes of genomic stability maintenance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ultraviolet B radiation (UVBR) induces the formation of photolesions in epidermal keratinocytes, potentially affecting cellular function and contributing towards malignant transformation. Insulin-like growth factor-I (IGF-I) contributes to protection of keratinocytes against UVBR-induced damage. Studies have shown that exogenous IGF-I or dermal fibroblast conditioned media pre-UVBR contributes to protection in primary keratinocytes by preventing apoptosis, modulating cell cycle progression and affecting photolesion removal through its damage preventative effects, however, the efficacy of IGF-I post-UVBR has not been sufficiently addressed. Using 2D and 3D photobiology skin models, the ability of IGF-I post-UVBR to rescue primary keratinocytes from photodamage was investigated. The photoprotective effect of IGF-I, both pre- and post-UVBR on cellular functions of irradiated keratinocytes was examined. IGF-I application, either pre- or post-UVBR, was found to alter keratinocyte survival, apoptosis, cell cycle progression and damage removal responses to UVBR. In particular, IGF-I application post-UVBR was found to promote increased keratinocyte survival, prevent apoptosis, shift cell cycle progression and reduce photodamage in all the skin models. Furthermore, marked differences were observed in activation of signalling cascades upon IGF-I treatment post-UVBR. Taken together, these findings indicate that in addition to a previously known photodamage preventative effect, IGF-I treatment post-UVBR has a photoreparative role suggesting it may hold potential in the development of effective remedial strategies against sunburns and photodamage., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Polarization status of tumor-associated macrophages (TAMs) plays an essential role in tumor growth and invasion. However, emerging treatment like photothermal therapy (PTT), photodynamic therapy (PDT) paid little attention on TAMs. In recent years, photothermal therapy (PTT) has gained immense attention in the anti-tumor strategy field while the effect of PTT on macrophage polarization in a tumor microenvironment has rarely been reported. Here, we used graphene oxide (GO) combined with polyethylene glycol (PEG) as the photothermal material to induce heating effect in macrophages to define its anti-tumor effect in vitro and in vivo. Firstly, we treated the macrophage cell line RAW264.7 with near infrared (NIR) light irradiation and detected their polarization status by flow cytometric and mRNA expression analysis. Following this, we analyzed the migration and invasion ability of an osteosarcoma HOS cell line cultured in a conditioned medium (CM) that contains cytokine generated by macrophages with or without NIR treatment. Finally, we investigated the in vivo effects of NIR-induced macrophage polarization on osteosarcoma growth and invasion. GO-PEG (GP) showed great photothermal effect, thermal stability, and biocompatibility in vitro and in vivo. Photothermal materials can alleviate interleukin-4-induced M2 polarization of macrophages and modulate their anti-tumor capability. Thus, the migration and invasion capabilities of HOS cells were weakened, leading to an anti-tumor effect in a mouse subcutaneous tumor model. In conclusion, our study identified PTT treatment as an approach for preventing osteosarcoma invasion by inhibition of M2 polarization., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest in this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Excessive exposure to UVB radiation can lead to oxidative and inflammatory damage that compromises the cutaneous integrity. The application on the skin of photochemoprotective products is considered a relevant approach for the prevention of oxidative damage. In this study the in vitro and in vivo photochemoprotective effects of antioxidant plant materials obtained from the leaves of Nectandra cuspidata Nees following UVB irradiation were evaluated. The cytoprotective effect, reactive oxygen species (ROS) production and lipid peroxidation (LPO) were assessed in L-929 fibroblasts treated with the ethyl acetate fraction (EAF) or isolated compounds (epicatechin, isovitexin and vitexin) before or after irradiation with UVB (500 mJ/cm 2 ). EAF substantially reduced the dead of cells and inhibited the UVB-induced ROS production and LPO in both treatments, compared with the irradiated untreated fibroblasts, presenting effects similar or better than pure compounds. The in vivo photochemoprotective effects of a topical emulsion containing 1% EAF (F2) were evaluated in hairless mice exposed to UVB. F2 improved all evaluated parameters in the skin of animals, inhibited ROS production, increased antioxidant defenses by decreasing reduced glutathione (GSH) and catalase depletion, reduced the activities of metalloproteinases (MMP-2 and MMP-9) and myeloperoxidase, decreased epidermal thickness and skin edema, and inhibited the appearance of sunburn cells as well as the recruitment of neutrophils and mast cell inflammatory infiltrates. These findings show that EAF presents high photochemoprotective effects, and that a topical formulation containing it may have potential for skin care., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Human dental pulp stem cells (hDPSCs) are able to differentiate into dopaminergic neurons and help the maintenance of partially degenerated neurons, which makes them as an alternative cell source for treatment of Parkinsons' disease (PD) patients. Here, the effect of photobiomodulation with polychromatic light source in the near infrared (NIR) range (600-1200 nm) or low level 660 nm diode laser light on hDPSCs during dopaminergic induction was investigated. Real time RT-qPCR analysis indicated that expressions of brain derived neurotrophic factor (BDNF), glial cell line derived neurotropic factor (GNDF), matrix associated protein 2 (MAP2), nuclear receptor related 1 protein (NURR1) and dopamine transporter (DAT) were increased, especially in the first 7 days of dopaminergic induction when 660 nm laser light was applied with a total energy density of 1.6 J/cm 2 . The activity of polychromatic light on hDPSCs depended on the differentiation media and protein type. BDNF, GDNF, NURR-1 and MAP2 expressions were increased in the presence of pre-induction factors, and decreased when the post-induction factors were added into the culture medium. In contrast with all these promising results, the dopaminergically induced hDPSCs did not show any functional characteristics of dopaminergic neurons and died after they were transferred to a new laminin coated culture plates. In conclusion, the expression of dopaminergic neuron protective protein mRNAs in hDPSCs was increased by photobiomodulation in defined conditions. However, the cells were not able to differentiate into functional dopaminergic neurons either in control or in photobiomodulated groups that are prone to cell death and exhibit immature dopaminergic neuron characteristics., Competing Interests: Declaration of Competing Interest Authors declare that they have no conflict of interest., (Copyright © 2019. Published by Elsevier B.V.)

Suitable properties as well as eco-friendly synthesis of photoluminescent Au nanoclusters (NCs) make them promising compounds for biomedical diagnostics and visualization applications. However, the potential photochemical activity of such agents on cancerous cells is largely unknown. The nanoclusters (BSA-Au NCs) were synthetized in the presence of BSA (an average hydrodynamic diameter was about 9.4 nm, while the size of the metal cluster was <1.3 nm according to atomic force microscopy measurements) and possessed a broad photoluminescence band at 680 nm in buffered (pH 7.2) aqueous medium. The photochemical activity was studied by adding two fluorescent probes (dihydrorhodamine or Singlet Oxygen Sensor Green) for detection of reactive oxygen species in samples irradiated at 405 nm to minimize direct excitation of the probes. The photoluminescence measurements evidenced the capability of BSA-Au NCs to generate reactive oxygen species upon light exposure, while the observed sensitivity of the photoluminescence properties might be used to indicate photooxidative processes in the medium. The viability test performed on breast cancer cells after incubation with BSA-Au NCs and subsequent irradiation revealed notable difference in induced phototoxicity between two cell lines, which was not the case after the corresponding treatment using the photosensitizer chlorin e 6 ., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Although the photothermal therapy (PTT) has achieved tremendous progress in the recent times, still it has to improve an extensive way to achieve the efficient targeted photothermal removal of the tumor cells. Owing to this requirement, we demonstrated a novel class of reduced graphene oxide based photothermal therapeutic agent for the ablation of lung cancer cells (A549). A single step bio facile fabrication of graphene nanosheets using Memecylon edule leaf extract intermediated reduction of Graphene Oxide (GO). This process does not include the utilization of any toxic or harmful reducing agents. The relative results of different characterizations of graphene oxide and Memecylon edule leaf extract RGO delivers a potential representation by excluding the groups containing oxygen from GO and consecutive stabilization of the developed RGO. The reduced GO functionalization with the oxidized polyphenols results in their stability by avoiding the aggregation. The poly phenol anchored Reduced Graphene Oxide (RGO) exhibited exceptional near-infrared (NIR) irradiation of the lung cancer cells directed in vitro to deliver cytotoxicity. In an area of restricted success in the treatment of cancer, the results of our translation can provide a path for designing targeted PTT agents and also responds to stimulus environment for the safe ablation of the devastating disease., (Copyright © 2019. Published by Elsevier B.V.)

Photothermal therapy (PTT) is recently clinically established cancer therapy that uses near-infrared light for thermal ablation of solid tumors. The biopolymer N-dihydrogalactochitosan (GC) was shown in multiple reports to act as a very effective adjunct to tumor PTT. In the present study, mouse tumor model SCCVII (squamous cell carcinoma) was used with two protocols, in situ tumor PTT and therapeutic PTT vaccine for tumors, for investigating the effects of GC. The results reveal that GC can potentiate tumoricidal action of PTT through both direct and indirect mechanisms. In addition to previously known capacity of GC for activating immune effector cells, the indirect means is shown to include reducing the populations of immunoregulatory T cells (Tregs) in PTT-treated tumors. Testing the effects of GC on PTT-treated SCCVII tumor cells in vitro uncovered the existence of a direct mechanism evident by reduced colony survival of these cells. Fluorescence microscopy demonstrated increased binding of fluorescein-labeled GC to PTT-treated compared to untreated SCCVII cells that can be blocked by pre-exposure to annexin V. The results of additional in vitro testing with specific inhibitors demonstrate that these direct mechanisms do not involve the engagement of death surface receptors that trigger extrinsic apoptosis pathway signaling but may be linked to pro-survival activity of caspase-1. Based on the latter, it can be suggested that GC-promoted killing of PTT-treated cells stems from interference of GC bound to damaged membrane components with the repair of these structures that consequently hinders cell survival., Competing Interests: Declaration of Competing Interest Tomas Hode and Samuel S.K. Lam declare a conflict of interest as employees of Immunophotonics Inc. which manufactures N-dihydrogalactochitosan. The other authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The graphene-based nanomaterials have been measured as a most promising nanomaterials in the various fields. Graphene oxide having attractive and effective attention in the modified of medicine. Also, graphene oxide is one of the distinct bio-chemical properties with minimum cytotoxicity compared to the other nanomaterials. Up to till date, gastric treatments with reduced graphene oxide not studied so far. In this report, 7-ethyl- 10-hydroxycamptothecin (SN-38) coated graphene oxide synthesized (SN-rGO) effectively and are characterized using various analytical methods. The hydroxyl and carbonyl gatherings of oxidized SN38 will in general ingest onto GO by means of hydrogen bond arrangement with their leftover oxygen functionalities and offers steadiness to SN38. The morphological analyses showed the foldable fields of SN38-rGO NPs with acquire transparency, thin sheets and the crumpled structures. Further the photothermal efficiency and cytotoxicity of the SN-rGO were examined by MTT assay using two NCI-N87 and SGC-791 gastric carcinoma cells. In addition, the morphological changes were examined through the live and dead cells and nuclear staining biochemical techiniques and apoptosis were evaluated through flow cytometry analysis. Our result's suggested that the SN-38 coated reduced graphene oxide can be used for the photothermal treatment of gastric carcinoma for the future nanotechnology cancer therapies without using functionalized polymeric nanoparticles., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ultraviolet B (UVB) induces inflammation and causes skin aging. The signs of skin aging, such as wrinkles, discolored spots, loss of skin moisture, and disruption of the skin barrier, are mostly caused by inflammatory signaling among various skin layers. The cells on the outermost surface of the skin are keratinocytes; these cells protect the skin against environmental stress and play an important role in immunomodulation by secreting cytokines in response to environmental stress. In the present study, we found that UVB activates STAT1 to mediate inflammatory signaling, yet STAT1 (S272) and STAT (Y702) shows different responses against UVB exposure. Anhua drak tea is a post-fermented dark tea produced in Anhua and Xinhua country in Hunan province of China. Treatment with 2S,3R-6-methoxycarbonylgallocatechin (MCGE), an epigallocatechin gallate derivative isolated from black tea (Anhua dark tea), effectively suppresses STAT1 activation and inflammatory cytokines, and activates Nrf2 pathway to protect cells from reactive oxygen species production in UVB exposed keratinocyte cells (HaCaT). Interestingly, the effects of MCGE were independent on MAPK signaling pathway. Moreover, MCGE regulates inflammatory cytokines in monocyte-keratinocyte (THP-1, HaCaT) co-culture and macrophage differentiation models. These results suggest that MCGE potentially can be used as a photoprotective agent against UVB-induced inflammatory responses., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Metal nanostructures are promising agents sensitizing by laser light and X-ray in photothermal therapy (PTT) and radiotherapy (RT) of cancer that improve treatment strategies of cancer. Nanoscale platinum materials are favorable in nanomedicine applications. In this study, platinum nanoparticles (PtNPs) were synthesized and applied for cancer therapy upon 808-nm laser light and X-ray radiation, or their combination. Two power densities of laser (1.0 and 1.5 W cm -2 ) and three X-ray doses (2, 4 and 6 Gy) were selected for irradiation of B16/F10 cell line at 24 and 72 h-post treatment. The synthesized PtNPs had a spherical shape with a diameter of 12.2 ± 0.7 nm, and were cytocompatible up to 250 μg mL -1 . A photothermal conversion activity in a concentration-dependent manner at 72 h-post treatment was observed. Also, PtNPs represented cytotoxicity upon X-ray radiation doses of 2, 4, and 6 Gy after 24 h, while, 72-h time passing led to deeper outcomes. Dual radiation of laser light and X-ray into PtNPs considerably improved the treatment via reactive oxygen species (ROS) production. PtNPs can act as a novel dual absorber of laser light and X-ray, a common sensitizer, for treatment of cancer. The results of this study can be considered after further clinical investigations for treatment of tumor models., (Copyright © 2019. Published by Elsevier B.V.)

Despite the high in vitro efficacy of photodynamic therapeutics, lack of tumor targeting significantly reduces their in vivo efficacy and thus limits their clinical use. Photoimmunotherapy (PIT) is a new synthetic strategy to target and treat cancer by photodynamic therapy (PDT). In this study, we describe design and synthesis of a third-generation photosensitizer comprising a PEGylated-phthalocyanine star-polymer photosensitizer that covalently bound to a myeloma tumor-selective antibody (MAb) via the carbodiimide chemistry. The free photosensitizer demonstrated a minimum dark toxicity when tested in mammalian myeloma cell line (SP2/OR); and a moderate phototoxicity after irradiation with non thermal laser red light as a result of light-induced production of cytotoxic singlet oxygen species. Covalent attachment of the photosensitizer (Pc) to the MAb resulted in a significantly enhanced phototoxicity. This is mainly ascribed to the fact that internalization enhances phototoxicity of Pc-MAb bioconjugates. The radioactivated photoimmuno-conjugates 131 I(PcMAb) demonstrated the highest phototoxicity to myeloma cells. The suggested bioconjugates are promising candidates as multiple therapeutic models for in vivo treatment of myeloma., (Copyright © 2020. Published by Elsevier B.V.)

This study aimed to compare the synthesis and secretion of VEGF-A, VEGF-C, VEGF-D, VEGFR1, VEGFR2, and FGF-2 between pulp fibroblasts from human primary teeth (HPF) and stem cell from human deciduous teeth (SHED) before and after photobiomodulation. HPF were obtained from explant technique and characterized by immunohistochemistry, while SHED were obtained from digestion technique and characterized by flow cytometry. HPF (control group) and SHED were plated, let to adhere, and put on serum starvation to synchronize the cell cycles prior to photobiomodulation. Then, both cell lineages were irradiated with 660-nm laser according to the following groups: 2.5 and 3.7 J/cm 2 . MTT and crystal violet assays respectively verified viability and proliferation. ELISA Multiplex Assay assessed the following proteins: VEGF-A, VEGF-C, VEGF-D, VEGFR1, VEGFR2, FGF-2, at 6, 12, and 24 h after photobiomodulation, in supernatant and lysate. Two-way ANOVA/Tukey test evaluated cell viability and proliferation, while angiogenic production and secretion values were analyzed by one-way ANOVA (P < .05). Statistically similar HPF and SHED viability and proliferation patterns occurred before and after photobiomodulation (P > .05). HPF exhibited statistically greater values of all angiogenic proteins than did SHED, at all study periods, except for FGF-2 (supernatant; 12 h); VEGFR1 (lysate; non-irradiated; 12 h); and VEGFR1 (lysate; non-irradiated; 24 h). Photobiomodulation changed the synthesis and secretion of angiogenic proteins by HPF. HPF produced and secreted greater values of all tested angiogenic proteins than did SHED before and after irradiation with both energy densities of 2.5 and 3.7 J/cm 2 ., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The goal of the current experiment is to explore the influence of combined and/or single applications of red and near infrared (NIR) photobiomodulation (PBM) at different wavelengths, energy densities and times on cell viability, population doubling time (PDT), and apoptosis of in vitro cultures of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and h adipose-derived stem cells (hASCs). Both in vitro hBM-MSCs and hASCs were irradiated with 36 protocols using two different laser types (helium‑neon [He-Ne] and diodes), four different laser wavelengths (HeNe laser, 630 nm, 810 nm, 630 + 810 nm); three different energy densities (0.6 J/cm 2 , 1.2 J/cm 2 , 2.4 J/cm 2 ); and three different PBM times (1, 2, and 3). One-way ANOVA analysis showed that PBM with the 630 nm red laser significantly stimulated cellular viability of both hBM-MSCs and hASCs. The 630 nm red laser significantly decreased PDT of hBM-MSCs. One-way ANOVA demonstrated that the 630 + 810 laser significantly stimulated cellular viability, and significantly decreased PDT and apoptosis of hBM-MSCs and hASCs. Two-way ANOVA analysis showed that PBM with the 630 nm red laser and 630 + 810 nm laser significantly stimulated cellular viability of hASCs compared to the control hASCs, and experimental and control hBM-MSCs. Our study demonstrated that PBM with the combined 630 + 810 nm lasers significantly stimulated cell viability, and significantly decreased PDT and apoptosis of hBM-MSCs and hASCs in vitro. We reported new in vitro evidence where PBM administered at 630 nm (one and two times, 0.6 and 1.2 J/cm 2 ) and 630 + 810 nm (three times, 2.4 J/cm 2 ) significantly increased hASC cell viability compared to its control and the PBM-treated hBM-MSC groups., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In the present study, we assessed the oral mucosal irritation potential of antimicrobial chemotherapy involving hydrogen peroxide (H 2 O 2 ) photolysis with a 405-nm laser device at an output power of ≥100 mW in hamsters. Twenty-four cheek pouches from 12 male Syrian hamsters received 7-min treatment with pure water (PW), 3% H 2 O 2 , laser irradiation of PW at 100 mW, laser irradiation of 3% H 2 O 2 at 100 mW, laser irradiation of PW at 200 mW, or laser irradiation of 3% H 2 O 2 at 200 mW (n = 4 each). The diameter of the irradiation area was set at 3 mm; accordingly, the calculated irradiances (optical power densities) of the 100- and 200-mW laser lights were approximately 1400 and 2800 mW/cm 2 , respectively. In addition, 12 cheek pouches from six animals received laser irradiation of 3% H 2 O 2 at 100 mW for 1, 3, or 5 min (n = 4 each). Each treatment was repeated three times at 1-h intervals. Macroscopic and histological changes were evaluated 24 h after the last treatment. In addition, in vitro bactericidal activity of the treatment against periodontal pathogens was evaluated. We found that 405-nm laser irradiation of 3% H 2 O 2 caused moderate to severe oral mucosal irritation when performed at powers of 100 and 200 mW for ≥3 min, while the same treatment performed at 100 mW for 1 min resulted in mild irritation. Moreover, 1-min H 2 O 2 photolysis at 100 mW caused a >4-log decrease in viable bacterial counts. These findings suggest that 1-min H 2 O 2 photolysis, which can effectively kill periodontal pathogens, may be acceptable when a 405-nm laser device is used at 100 mW. However, use of the laser at a lower power would be preferable for the prevention of unnecessary oral mucosal irritation., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Photodynamic therapy (PDT) is a non-invasive FDA and EMA-approved anticancer treatment modality. Initially developed for elimination of malignant cells, PDT affects all cells in the tumor bed including stromal cells. Stroma represents not only an important component of tumor microenvironment, but has a significant impact on tumor susceptibility to PDT and other anticancer therapies. However, the effects of PDT on stromal cells are poorly investigated. During PDT the tumor stroma can receive low-dose irradiation as a result of chosen regimen or limited depth of light penetration. Here, we characterized response of human mesenchymal stromal cells (MSCs) to low-dose PDT. In an in vitro model we demonstrated that low-dose PDT resulted in activation of Erk1/2 and inhibition of GSK-3 signaling in MSCs. PDT-mediated induction of intracellular reactive oxygen species (ROS) resulted in reorganization of MSC cytoskeleton and decreased cell motility. More importantly, low-dose PDT dramatically upregulated secretion of various proangiogenic factors (VEGF-A, IL-8, PAI-1, MMP-9, etc.) by MSCs and improved MSC ability to promote angiogenesis suggesting an increase in the pro-tumorigenic potential of MSCs. In contrast, co-cultivation of PDT-treated MSCs with lymphocytes resulted in significant decrease of MSC viability and potential increase in MSC immunogenicity, which may lead to increased anti-tumor immunity. Low-dose PDT in MSCs significantly inhibited secretion of CCL2 (MCP-1) potentially limiting infiltration of pro-tumorigenic macrophages. Altogether, our findings demonstrate that low-dose PDT significantly modifies functional properties of MSCs improving their pro-tumorigenic potential while simultaneously increasing potential immune stimulation suggesting possible mechanisms of stromal cell contribution to PDT efficacy., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Previous studies revealed significant impact on cancer cell by mid-infrared (MIR) radiation. However, the effects of narrow band MIR on immune reaction and infectious disease are still unknown. In this study, an enhanced innate immune response was observed through the interaction between Leptospiral outer membrane protein (LipL32) and toll-like receptor 2 (TLR2). Thereafter, human kidney proximal tubular cells (HK-2 cells) initiated a serial reaction of enhanced MCP-1 production. The 6 μm narrow bandwidth light source emitted by waveguide thermal emitter (WTE) was applied to induce carbonyl group (CO bond) stretching vibration during the stage of antigen-receptor complex formation. The amount of MCP-1 gene expression had 2.5 folds increase after narrow band MIR illumination comparing to non-MIR illumination at low dose LipL32 condition. Besides, both ELISA and confocal microscopy results also revealed that the chemokine concentration increased significantly after narrow band MIR illumination either at low or high concentration of LipL32. Furthermore, a specific phenomenon that narrow band MIR can amplify the signal of weak immune response by enhancing sensitivity of the interaction between antigen and receptor was observed. This study exhibits clear evidence that the narrow band MIR exposure can modulate the early immune response of infectious disease and play a potential role to develop host-directed therapy in the future., (Copyright © 2019 Elsevier B.V. All rights reserved.)

High disappointment rate of the ligament to hard tissue mending after the medical procedure has dependably been a testing issue in rotator cuff repair. Considering the elasticity of carbon dot decorated polyethylene (f-CDs-PE) and osteogenic movement of gold substituted hydroxyapatite (Au@HA) bioceramic, f-CDs-PE-Au@HA biocomposite coatings were created by an electrophoretic deposition method (EPD), the in vivo and in vitro bioactivity and cytocompatibility were researched. The physico-chemical properties of f-CDs-PE-Au@HA biocomposite coatings were characterized using fourier transform infra-red (FTIR) and X-Ray diffractometery (XRD). The morphology of the fabricated biocomposites was analyses via scanning electron microscopy (SEM) and transmission electron microscopy (TEM) methods. With a gamma-irradiation of f-CDs-PE-Au@HA biocomposite coating (BC 2 ), the bond and multiplication of cells on biocomposite coating were improved. The specimen with a f-CDs-PE-Au@HA biocomposite (BC 2 ) demonstrated a most noteworthy alkaline phosphatase activity articulation. The animal model consequences additionally show that the f-CDs-PE-Au@HA biocomposite (BC 2 ) had great bioactive and cytocompatibility, which could develop the association of collagen and the arrangement of ligament and hard tissue. Expansion of the gamma-ray irradiation with f-CDs-PE-Au@HA biocomposite coating (BC 2 ) at the tendon- hard tissue crossing point was exhibited to reinforce the mending entheses, increment hard tissue and tendon development and progress collagen association contrasted and control. The above outcomes have recommended that the progressive, implantable and solid stringy platforms built utilizing EPD extraordinary potential for enlargement of rotator cuff tears-recuperating., (Copyright © 2019 Elsevier B.V. All rights reserved.)