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1.
Artículo en Inglés | MEDLINE | ID: mdl-38570275

RESUMEN

OBJECTIVE: To evaluate the occurrence of genotoxic and cytotoxic effects in oral epithelium after exposure of patients to cone beam computed tomography (CBCT). METHODS: A systematic review (SR) was conducted following the PECO (Population, Exposure, Comparison, Outcome) criteria. The study was registered in the International Prospective Register of Systematic Reviews (PROSPERO). A search was performed on the PubMed, Scopus, ScienceDirect, and Google Scholar databases. Effect size and heterogeneity of data were evaluated statistically. The Joanna Briggs Institute questionnaire for observational studies was utilized to assess the risk of bias. The GRADE tool was applied for the assessment of the quality of evidence. Begg's funnel plot was used to evaluate publication bias. RESULTS: In total, 10 full-text articles were included in the SR, with 6 of them in the meta-analysis. The SR showed a significant increase in micronuclei after exposure, with a large effect size of 1.03. For genotoxicity, the tau2 for heterogeneity was 0.96, the chi-squared test for heterogeneity P < .00001, the I2 statistics for random effects was 91%, and the overall effect for Z value was 2.46 (P = .01). The risk of bias was low, the quality of evidence was strong, and publication bias was absent. CONCLUSION: CBCT can cause genotoxicity in the oral epithelium with a large effect size. The measure of cytotoxicity after CBCT exposure was not possible due to the lack of homogeneity of the included articles.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Mucosa Bucal , Humanos , Tomografía Computarizada de Haz Cónico/efectos adversos , Daño del ADN , Epitelio/diagnóstico por imagen , Epitelio/efectos de la radiación , Mucosa Bucal/diagnóstico por imagen , Mucosa Bucal/efectos de la radiación
2.
J Photochem Photobiol B ; 255: 112908, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38663336

RESUMEN

The prevalence of Light-emitting diodes (LEDs) has exposed us to an excessive amount of blue light (BL) which causes various ophthalmic diseases. Previous studies have shown that conjunctiva is vulnerable to BL. In this study, we aimed to investigate the underlying mechanism of BL-induced injury in conjunctiva. We placed C57BL/6 mice and human conjunctival epithelial cell lines (HCECs) under BL (440 nm ± 15 nm, 0.2 mW/cm2) to establish a BL injury model in vivo and in vitro. Immunohistochemistry and MDA assay were used to identify lipid peroxidation (LPO) in vivo. HE staining was applied to detect morphological damage of conjunctival epithelium. DCFH-DA, C11-BODIPY 581/591, Calcein-AM, and FeRhoNox™-1 probes were performed to identify ferroptosis levels in vitro. Real-time qPCR and Western blotting techniques were employed to uncover signaling pathways of blue light-induced ferroptosis. Our findings demonstrated that BL affected tear film instability and induced conjunctival epithelium injury in vivo. Ferrostatin-1 significantly alleviated blue light-induced ferroptosis in vivo and in vitro. BL downregulates the levels of solute carrier family 7 member 11 (SLC7A11), Ferritin heavy chain (FTH1), and glutathione peroxidase (GPX4) by inhibiting the activation and translocation of the Signal transducer and activator of transcription 3 (STAT3) from inducing Fe2+ burst, ROS and LPO accumulation, ultimately resulting in ferroptosis. This study will offer new insight into BL-induced conjunctival injury and LED-induced dry eye.


Asunto(s)
Luz Azul , Conjuntiva , Ferroptosis , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Factor de Transcripción STAT3 , Animales , Humanos , Ratones , Sistema de Transporte de Aminoácidos y+/metabolismo , Sistema de Transporte de Aminoácidos y+/genética , Línea Celular , Conjuntiva/metabolismo , Conjuntiva/efectos de la radiación , Conjuntiva/patología , Ciclohexilaminas , Células Epiteliales/metabolismo , Células Epiteliales/efectos de la radiación , Células Epiteliales/patología , Epitelio/efectos de la radiación , Epitelio/metabolismo , Epitelio/patología , Ferroptosis/efectos de la radiación , Peroxidación de Lípido/efectos de la radiación , Ratones Endogámicos C57BL , Fenilendiaminas/farmacología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de la radiación , Factor de Transcripción STAT3/metabolismo
3.
Arch Oral Biol ; 142: 105525, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36027639

RESUMEN

OBJECTIVES: The aim of this study was to assess the MUC1 expression in the oral epithelium of normal, oral epithelial dysplasia (OED), oral squamous cell carcinoma (OSCC), and irradiated oral epithelium (IROE) and its association with smoking habits in non-smokers and smokers. DESIGN: Oral mucosal biopsies from controls, OED, OSCC, and IROE groups were obtained and categorized based on the smoking history as non-smokers, smoker I (25 pack-years), and smoker II (>25 pack-years). Immunohistochemical staining of MUC1 using human milk fat globule 1 (HMFG 1) antibody was performed, and the MUC1 score was calculated. The relation between MUC1 expression and clinicopathological findings was examined. RESULTS: MUC1 staining of superficial oral epithelial cells with mild MUC1 score was detected in all control samples. The MUC1 staining extended from superficial to basal cell layer of oral epithelium with the increase in MUC1 score from moderate to strong in OED, OSCC, and IROE, and the difference was significant (p < 0.004, p < 0.002 and p < 0.004, respectively) compared to controls. A positive association between smoking and MUC1 score was observed within groups (p < 0.05). CONCLUSION: The depolarization of MUC1 protein expression is associated with smoking habits in OED and OSCC. In the IROE, the radiation causes subcellular and molecular changes, observed as altered MUC1 expression and accelerated by smoking, furthermore, complicating the oral mucosal adaptation and progress to radiation-induced lesions as a delayed effect.


Asunto(s)
Carcinoma de Células Escamosas , Mucina-1 , Fumar , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Epitelio/metabolismo , Epitelio/patología , Epitelio/efectos de la radiación , Humanos , Mucosa Bucal/metabolismo , Mucosa Bucal/patología , Mucosa Bucal/efectos de la radiación , Neoplasias de la Boca/genética , Neoplasias de la Boca/patología , Mucina-1/metabolismo , Fumar/efectos adversos
4.
Reprod Biol ; 21(4): 100564, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34662815

RESUMEN

Endometrial regeneration is a dynamic process that is not well understood. The destruction of the endometrium with the formation of intrauterine adhesions is known as Asherman's syndrome. The lesions range from minor to severe adhesions and their impact on pregnancy is well documented. Operative hysteroscopy is the mainstay of diagnosis and treatment of intrauterine adhesions. Nevertheless, the recurrence rates remain high. It was recorded that low-level laser therapy in low doses has a stimulatory effect on different tissues while the high dose produces a suppressive effect. Organoid is a three-dimensional assembly that displays architectures and functionalities similar to in vivo organs that are being developed from human or animal stem cells or organ-specific progenitors through a self-organization process. Our prospective was to study the effect of Low-Level Laser Therapy (LLLT) on mouse epithelial endometrial organoids regarding cell proliferation and endometrial regeneration as a new modality of treatment. An in vitro clinical trial to generate mouse epithelial organoid model and testing LLLT using He:Ne 632.8 nm device on organoids proliferation, function, and their response to ovarian hormones was performed. Trying endometrial regeneration by culturing organoids with decellularized uterine matrix (DUM) and studying the LLLT effect on the regeneration process. LLLT produced a proliferative effect on the epithelial mouse organoids confirmed by Ki67 and PCNA IHC. The organoids could regenerate the epithelial layer of the endometrium in vitro on DUM and LLLT could help in this process. In conclusion, organoids whether control or bio-stimulated proved a new modality to regenerate the endometrium.


Asunto(s)
Endometrio/efectos de la radiación , Técnicas In Vitro , Terapia por Luz de Baja Intensidad , Organoides/efectos de la radiación , Regeneración/efectos de la radiación , Animales , Proliferación Celular/efectos de la radiación , Epitelio/efectos de la radiación , Femenino , Ginatresia/radioterapia , Ratones
5.
J Photochem Photobiol B ; 225: 112332, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34653929

RESUMEN

Skin wounds represent a burden in healthcare. Our aim was to investigate for the first time the effects of defocused high-power diode laser (DHPL) on skin healing in an animal experimental model and compare it with gold standard low-level laser therapy. Male Wistar rats were divided into 5 groups: Negative control; Sham; 0.1 W laser (L0.1 W); DHPL Dual 1 W (DHPLD1 W); and DHPL Dual 2 W (DHPLD2 W). Rats were euthanized on days 3, 5, 10, 14 and 21. Clinical, morphological, PicroSirus, oxidative stress (MDA, SOD and GSH) and cytokines (IL-1ß, IL-10 and TNF-α) analyses were performed. A faster clinical repair was observed in all laser groups at D10 and D14. DHPLD1 W exhibited lower inflammation and better reepithelization compared to other groups at D10. DHPL protocols modulated oxidative stress by decreasing MDA and increasing SOD and GSH. Collagen maturation was triggered by all protocols tested and L0.1 W modulated cytokines release (IL-1ß and TNF-α) at D3. In conclusion, DHPL, especially DHPL1 W protocol, accelerated skin healing by triggering reepithelization and collagen maturation and modulating inflammation and oxidative stress.


Asunto(s)
Colágeno/metabolismo , Terapia por Láser/métodos , Piel/fisiopatología , Cicatrización de Heridas/efectos de la radiación , Animales , Citocinas/metabolismo , Epitelio/crecimiento & desarrollo , Epitelio/efectos de la radiación , Inflamación/prevención & control , Masculino , Oxidación-Reducción , Estrés Oxidativo/efectos de la radiación , Ratas , Ratas Wistar , Piel/metabolismo
6.
Cancer Res ; 81(18): 4808-4821, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34321243

RESUMEN

In studies of electron and proton radiotherapy, ultrahigh dose rates of FLASH radiotherapy appear to produce fewer toxicities than standard dose rates while maintaining local tumor control. FLASH-proton radiotherapy (F-PRT) brings the spatial advantages of PRT to FLASH dose rates (>40 Gy/second), making it important to understand if and how F-PRT spares normal tissues while providing antitumor efficacy that is equivalent to standard-proton radiotherapy (S-PRT). Here we studied PRT damage to skin and mesenchymal tissues of muscle and bone and found that F-PRT of the C57BL/6 murine hind leg produced fewer severe toxicities leading to death or requiring euthanasia than S-PRT of the same dose. RNA-seq analyses of murine skin and bone revealed pathways upregulated by S-PRT yet unaltered by F-PRT, such as apoptosis signaling and keratinocyte differentiation in skin, as well as osteoclast differentiation and chondrocyte development in bone. Corroborating these findings, F-PRT reduced skin injury, stem cell depletion, and inflammation, mitigated late effects including lymphedema, and decreased histopathologically detected myofiber atrophy, bone resorption, hair follicle atrophy, and epidermal hyperplasia. F-PRT was equipotent to S-PRT in control of two murine sarcoma models, including at an orthotopic intramuscular site, thereby establishing its relevance to mesenchymal cancers. Finally, S-PRT produced greater increases in TGFß1 in murine skin and the skin of canines enrolled in a phase I study of F-PRT versus S-PRT. Collectively, these data provide novel insights into F-PRT-mediated tissue sparing and support its ongoing investigation in applications that would benefit from this sparing of skin and mesenchymal tissues. SIGNIFICANCE: These findings will spur investigation of FLASH radiotherapy in sarcoma and additional cancers where mesenchymal tissues are at risk, including head and neck cancer, breast cancer, and pelvic malignancies.


Asunto(s)
Epitelio , Tratamientos Conservadores del Órgano , Terapia de Protones , Sarcoma/patología , Sarcoma/radioterapia , Animales , Huesos/patología , Huesos/efectos de la radiación , Modelos Animales de Enfermedad , Perros , Epitelio/efectos de la radiación , Femenino , Perfilación de la Expresión Génica , Humanos , Ratones , Morbilidad , Músculos/patología , Músculos/efectos de la radiación , Tratamientos Conservadores del Órgano/métodos , Terapia de Protones/efectos adversos , Terapia de Protones/métodos , Traumatismos por Radiación/diagnóstico , Traumatismos por Radiación/etiología , Dosificación Radioterapéutica , Sarcoma/metabolismo , Piel/efectos de la radiación , Resultado del Tratamiento
7.
Sci Rep ; 11(1): 10230, 2021 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-33986410

RESUMEN

Radon is a leading cause of lung cancer in indoor public and mining workers. Inhaled radon progeny releases alpha particles, which can damage cells in the airway epithelium. The extent and complexity of cellular damage vary depending on the alpha particle's kinetic energy and cell characteristics. We developed a framework to quantitate the cellular damage on the nanometer and micrometer scales at different intensities of exposure to radon progenies Po-218 and Po-214. Energy depositions along the tracks of alpha particles that were slowing down were simulated on a nanometer scale using the Monte Carlo code Geant4-DNA. The nano-scaled track histories in a 5 µm radius and 1 µm-thick cylindrical volume were integrated into the tracking scheme of alpha trajectories in a micron-scale bronchial epithelium segment in the user-written SNU-CDS program. Damage distribution in cellular DNA was estimated for six cell types in the epithelium. Deep-sited cell nuclei in the epithelium would have less chance of being hit, but DNA damage from a single hit would be more serious, because low-energy alpha particles of high LET would hit the nuclei. The greater damage in deep-sited nuclei was due to the 7.69 MeV alpha particles emitted from Po-214. From daily work under 1 WL of radon concentration, basal cells would respond with the highest portion of complex DSBs among the suspected progenitor cells in the most exposed regions of the lung epithelium.


Asunto(s)
Bronquios/efectos de la radiación , Radón/efectos adversos , Mucosa Respiratoria/efectos de la radiación , Partículas alfa , Bronquios/metabolismo , Epitelio/química , Epitelio/efectos de la radiación , Humanos , Pulmón/química , Pulmón/efectos de la radiación , Modelos Biológicos , Método de Montecarlo , Dosis de Radiación , Radón/análisis , Hijas del Radón/efectos adversos , Hijas del Radón/análisis , Mucosa Respiratoria/química , Mucosa Respiratoria/metabolismo
8.
Radiat Res ; 195(3): 265-274, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33400793

RESUMEN

Tritium has been receiving worldwide attention, particularly because of its production and use in existing fission reactors and future nuclear fusion technologies, leading to an increased risk of release in the environment. Linking human health effects to low-dose tritium exposures presents a challenge for many reasons. Among these: biological effects strongly depend on the speciation of tritiated products and exposure pathway; large dosimetric uncertainties may exist; measurements using in vitro cell cultures generally lack a description of effects at the tissue level, while large-scale animal studies might be ethically questionable and too highly demanding in terms of resources. In this context, three-dimensional models of the human airway epithelium are a powerful tool to investigate potential toxicity induced upon inhalation of radioactive products in controlled physiological conditions. In this study we exposed such a model to tritiated water (HTO) for 24 h, with a range of activity levels (up to ∼33 kBq µl-1 cm-2). After the exposures, we measured cell viability, integrity of epithelial layer and pro-inflammatory response at different post-exposure time-points. We also quantified tritium absorption and performed dosimetric estimates considering HTO passage through the epithelial layer, leading to reconstructed upper limits for the dose to the tissue of less than 50 cGy cumulative dose for the highest activity. Upon exposure to the highest activity, cell viability was not decreased; however, we observed a small effect on epithelial integrity and an inflammatory response persisting after seven days. These results represent a reference condition and will guide future experiments using human airway epithelium to investigate the effects of other peculiar tritiated products.


Asunto(s)
Epitelio/efectos de la radiación , Pulmón/efectos de la radiación , Tritio/efectos adversos , Agua/química , Animales , Epitelio/patología , Humanos , Pulmón/patología , Ratones , Radiometría
9.
Lasers Med Sci ; 36(4): 863-870, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32827076

RESUMEN

Ultraviolet radiation (UVR) is the major etiologic agent of cutaneous photoaging, and different strategies are used to prevent and treat this condition. The polysaccharide fraction (LBPF) isolated from Lycium Barbarum fruits (goji berry) contains several active ingredients with antioxidant, immune system modulation, and antitumor effects. In addition, the photobiomodulation (PBM) is widely applied in photoaging treatment. This study investigated the effects of LBPF and PBM against the UVR-induced photodamage in the skin of hairless mice. The mice were photoaged for 6 weeks in a chronic and cumulative exposure regimen using a 300-W incandescent lamp that simulates the UVR effects. From the third to the sixth week of photoaging induction, the animals received topical applications of LBPF and PBM, singly or combined, in different orders (first LBPF and then PBM and inversely), three times per week after each session of photoaging. After completion of experiments, the dorsal region skin was collected for the analysis of thickness, collagen content, and metalloproteinases (MMP) levels. A photoprotective potential against the increase of the epithelium thickness and the fragmentation of the collagen fibers was achieved in the skin of mice treated with LBPF or PBM singly, as well as their combination. All treatments maintained the skin collagen composition, except when PBM was applied after the LBPF. However, no treatment protected against the UVR-induced MMP increase. Taken together, we have shown that the LBPF and PBM promote a photoprotective effect in hairless mice skin against epidermal thickening and low collagen density. Both strategies, singly and combined, can be used to reduce the UVR-induced cutaneous photoaging.


Asunto(s)
Colágeno/metabolismo , Medicamentos Herbarios Chinos/farmacología , Epitelio/efectos de los fármacos , Epitelio/efectos de la radiación , Terapia por Luz de Baja Intensidad , Piel/patología , Piel/efectos de la radiación , Animales , Epitelio/patología , Ratones , Ratones Pelados , Piel/efectos de los fármacos , Piel/metabolismo , Envejecimiento de la Piel/efectos de los fármacos , Envejecimiento de la Piel/patología , Envejecimiento de la Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos
10.
J Photochem Photobiol B ; 213: 112058, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-33147556

RESUMEN

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/m2 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.


Asunto(s)
Epitelio/efectos de la radiación , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Cristalino/efectos de la radiación , Epitelio Pigmentado de la Retina/efectos de la radiación , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Apoptosis/efectos de la radiación , Línea Celular , Supervivencia Celular/efectos de la radiación , Quinasas MAP Reguladas por Señal Extracelular , Humanos , Cristalino/citología , Sistema de Señalización de MAP Quinasas , Estrés Oxidativo , Fosforilación/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Epitelio Pigmentado de la Retina/citología , Transducción de Señal , Luz Solar
11.
Toxicology ; 442: 152536, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32649955

RESUMEN

Radiotherapy is one of the principal approaches employed in the treatment of pelvic cancers. Nevertheless, testicular dysfunction and infertility are among the most common adverse effects in young adult cancer survivors. Clinically, alpha-lipoic acid (LA) has been applied to improve the quality of sperm with a satisfactory effect. Therefore, the present study investigated the underlying mechanisms of the radioprotective effects of LA against testicular damage. Male Sprague-Dawley rats were exposed to 10 Gy of whole-body ϒ-radiation and LA (50 mg/kg, P.O.) was administered one week before and three days post-irradiation. LA showed remarkable capacity in preserving testicular tissue against radiation damage by improving histological and ultrastructural changes of disorganized seminiferous tubules, besides enhancing its diameter, germinal epithelial thickness, and Johnsen's score. Radiation instigated a significant decrease in sperm quality and quantity associated with depletion of serum testosterone levels, while the LA administration maintained spermatogenesis. Strikingly, LA exhibited antioxidant properties by restoring reduced glutathione levels and antioxidant enzyme activities such as catalase and glutathione-s-transferase, besides diminishing malondialdehyde levels in the testis of irradiated group. Furthermore, LA alleviated testicular inflammation through downregulation of nuclear factor-ĸB (NF-ĸB) expression with a subsequent reduction in interleukin (IL)-6 and cyclooxygenase-2 expression, accompanied by the augmented expression of the anti-inflammatory cytokine IL-10. Additionally, testicular fibrosis markers including Masson's trichrome and transforming growth factor (TGF)-ß expression were noticeably declined in LA-treated irradiated rats, together with the upregulation of peroxisome proliferator-activated receptor-ϒ expression. Collectively, LA ameliorates radiation-mediated spermatogenesis-defects and testicular-damage via suppression of oxidative stress/NF-ĸB/TGF-ß signaling.


Asunto(s)
Rayos gamma , Traumatismos Experimentales por Radiación/prevención & control , Protectores contra Radiación/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/efectos de la radiación , Enfermedades Testiculares/prevención & control , Ácido Tióctico/farmacología , Animales , Antioxidantes/farmacología , Citocinas/biosíntesis , Epitelio/efectos de los fármacos , Epitelio/efectos de la radiación , Masculino , FN-kappa B/efectos de los fármacos , FN-kappa B/efectos de la radiación , PPAR gamma/efectos de los fármacos , PPAR gamma/efectos de la radiación , Traumatismos Experimentales por Radiación/patología , Ratas , Ratas Sprague-Dawley , Espermatozoides/efectos de los fármacos , Espermatozoides/efectos de la radiación , Enfermedades Testiculares/patología , Testículo/patología , Testículo/efectos de la radiación , Testosterona/sangre , Factor de Crecimiento Transformador beta/efectos de los fármacos , Factor de Crecimiento Transformador beta/efectos de la radiación , Irradiación Corporal Total
12.
Mol Oncol ; 14(6): 1185-1206, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32336009

RESUMEN

Increasing evidence suggests that interference with growth factor receptor tyrosine kinase (RTK) signaling can affect DNA damage response (DDR) networks, with a consequent impact on cellular responses to DNA-damaging agents widely used in cancer treatment. In that respect, the MET RTK is deregulated in abundance and/or activity in a variety of human tumors. Using two proteomic techniques, we explored how disrupting MET signaling modulates global cellular phosphorylation response to ionizing radiation (IR). Following an immunoaffinity-based phosphoproteomic discovery survey, we selected candidate phosphorylation sites for extensive characterization by targeted proteomics focusing on phosphorylation sites in both signaling networks. Several substrates of the DDR were confirmed to be modulated by sequential MET inhibition and IR, or MET inhibition alone. Upon combined treatment, for two substrates, NUMA1 S395 and CHEK1 S345, the gain and loss of phosphorylation, respectively, were recapitulated using invivo tumor models by immunohistochemistry, with possible utility in future translational research. Overall, we have corroborated phosphorylation sites at the intersection between MET and the DDR signaling networks, and suggest that these represent a class of proteins at the interface between oncogene-driven proliferation and genomic stability.


Asunto(s)
Daño del ADN , Epitelio/patología , Mesodermo/patología , Fosfoproteínas/metabolismo , Proteómica , Animales , Línea Celular Tumoral , Reparación del ADN/efectos de la radiación , Regulación hacia Abajo/efectos de la radiación , Epitelio/efectos de la radiación , Femenino , Humanos , Mesodermo/efectos de la radiación , Ratones , Proteínas de Neoplasias/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación/efectos de la radiación , Radiación Ionizante , Reproducibilidad de los Resultados , Especificidad por Sustrato/efectos de la radiación , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Ecotoxicol Environ Saf ; 192: 110268, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32036099

RESUMEN

Present study highlighted the ultramicroscopic (SEM) alterations of the skin, eye, barbel, and fins of spawn of an air-breathing teleost (Clarias batrachus, Linn. 1758) induced by UV-B radiation (280-320 nm) at a dose (@4.07 × 10-20J/photon/m2) under the time-frame of 5, 10 and 15 min/d in the laboratory condition for the periods of 5 and 10 days. Limnological parameters revealed no significant changes throughout the period of experimentation which were measured by PCS Testr 35 Multi-Parameter. Morphometric analysis revealed that during the extended exposure period of 10 days the spawn size and weight were reduced as analysed through Specific Growth Rate (SGR). SGR values in terms of weight for 5 and 10 days under 3 time-frames were 17.12%, 12.52%, 11.46% and 9.09%, 6.43%, 6.09% respectively, which revealed a declined trend along with the exposure days. In the skin of C. batrachus, the compact regular orientation of the stratified epithelial cells and mucous cells became distorted and the microridges and double-ridged structures showed destruction and fragmentations. The body striations and microfolds became shrinked and swollen and finally degenerated to form a mass. The distribution of mucous cells throughout the epidermis was disorganised and releasing secretory contents on the surface through small pores. Appearance of huge quantity of biogenic semi-hexagonal plate like crystals (guanine platelets) on the skin surface of the body was the most significant observations during UV-B radiation. In the developmental phases the eyeball showed shrinkage loosing normal regular concave structure and to become a dome-shaped one. The supportive connective infoldings became loosened. The choroid coat displayed deformities and the iris deformed the pupil. The fibroblast on the epithelium and melanocytes depicted dispersed arrangement. The pairs of ventral barbels near the mouth depicted the presence of taste buds that became severely damaged exposing the sensory as well as neuroepithelial cells. Compact regular arrangement of the SECs was completely destroyed leaving long and deep channels inbetween them; the disintegrated concentric MRs also showed a mass.


Asunto(s)
Aletas de Animales/efectos de la radiación , Bagres , Ojo/efectos de la radiación , Piel/efectos de la radiación , Rayos Ultravioleta/efectos adversos , Aletas de Animales/ultraestructura , Animales , Relación Dosis-Respuesta en la Radiación , Epidermis/efectos de la radiación , Epidermis/ultraestructura , Epitelio/efectos de la radiación , Epitelio/ultraestructura , Ojo/ultraestructura , Piel/ultraestructura
14.
Photobiomodul Photomed Laser Surg ; 37(11): 715-721, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31580781

RESUMEN

Objective: The purposes of this split-mouth pilot study were to investigate the efficacy of the Er:YAG laser use for the de-epithelialization of the palatal graft in the treatment of the multiple gingival recessions using the bilaminar procedure and also to evaluate the patient-reported esthetic outcomes after 6 months. Materials and methods: Five systemically healthy participants with total 28 bilateral-multiple adjacent maxillary Miller I recessions were included. The treatment was performed with the bilaminar technique [coronally advanced flap (CAF)+de-epithelialized free gingival graft]. De-epithelialization procedure was done with scalpel (control site) or Er:YAG laser (Versawave, Hoya ConBio, San Francisco, CA; 40 hz, 50 mJ/pulse), under water irrigation, noncontact mode (∼1 mm away from the target tissue) in sweeping motion with chisel-type laser (test site). Root coverage and patient-reported outcomes were evaluated at 6 months after the operations. Results: Clinical outcomes of the both treatment sites did not show any statistically significant differences except for the gingival thickness parameter. However, patient-reported outcomes regarding the esthetic appearance of the gingiva was detected in favor of the Er:YAG laser applied sites. Conclusions: Within the limits of the study, it can be concluded that both de-epithelialization techniques were highly effective at 6 months. However, Er:YAG laser-applied grafted sites revealed more uniform and esthetic gingival appearance compared with scalpel-used grafted sites.


Asunto(s)
Tejido Conectivo/efectos de la radiación , Epitelio/efectos de la radiación , Recesión Gingival/cirugía , Láseres de Estado Sólido , Colgajos Quirúrgicos , Adulto , Tejido Conectivo/cirugía , Papila Dental/cirugía , Epitelio/cirugía , Estética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Hueso Paladar/cirugía , Satisfacción del Paciente , Proyectos Piloto
15.
Bratisl Lek Listy ; 120(4): 299-308, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31023054

RESUMEN

OBJECTIVES: The aim of the study was to investigate the possible effects of radiofrequency radiation (RFR) at different frequencies for different exposure durations on caspase-dependent apoptosis pathways in human colon adenocarcinoma (HT-29). METHODS: HT-29 cells were exposed to 1800 MHz; 2100 MHz and 2600 MHz RFR for 3 h cont., 6 h int. and 6 h cont.. Cell viability measurements were performed by Trypan Blue exclusion assay and the gene expressions of CASP8, CASP9, CASP3 and CASP12 were analyzed using qRT-PCR. RESULTS: Exposure to 2100 MHz RFR for all 3 durations of exposures was more effective for the ratio of the number of viable HT-29 cells w.r.t 1800 MHz RFR and 2600 MHz RFR exposures. After 2100 MHz RFR exposure, caspase activation increased significantly (for 3h cont. and 6 h int. exposures CASP8 and CASP9 levels; for 6 h cont. exposure CASP3 levels) (p 0.05). CONCLUSION: Decreases in the cell viability of HT-29 cells for certain frequencies and also durations are consistent with significant increases in caspase activations. The results of caspase activation after 1800 MHz or 2600 MHz RFR exposures can be interpreted as the activation of different types of cell death pathway by caspase signaling cascades (Fig. 15, Ref. 56).


Asunto(s)
Apoptosis , Colon , Ondas de Radio , Apoptosis/efectos de la radiación , Supervivencia Celular , Colon/efectos de la radiación , Epitelio/efectos de la radiación , Humanos
16.
Rom J Morphol Embryol ; 60(4): 1269-1273, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-32239104

RESUMEN

Functional and esthetic recovery of the patient after tooth extraction is a concern in the nowadays-dental medicine. Immediate implant placement in fresh sockets in posterior sides of the jaws is difficult because of the high amount of bone loss and the disparity between the diameter of the alveolus and the implant. The objective is to evaluate the effect of laser biomodulation alveolar socket healing process of healthy patients. A number of 36 molars have been extracted due to advanced caries lesions from the same dental arch but on opposite sites. Laser irradiation was performed on one side after extraction; the other side was used as control. An Epic-X laser diode (Biolase) Indium-Gallium-Arsenide-Phosphorus (In-Ga-As-P) 940 nm was used in a continuous mode, 0.9 W, 36 J for 80 seconds, daily exposure, in the first seven days after extraction. Specimens of soft and hard tissue were surgically incised and removed by a 4.4 mm diameter trepan from the extraction sites, eight weeks after the surgical procedure. The specimens were prepared by use of two staining procedures: Hematoxylin-Eosin (HE) and Mallory's trichrome. The prepared slides were examined under Leica DM750 optical microscope, 5× and 10× magnification. Laser biomodulation therapy accelerates bone formation by increasing osteoblastic activity. The histological study demonstrates early new bone formation, the regeneration effects in fresh intact bony alveolus compared with the soft and bone regeneration level of non-treated fresh alveolus. Laser biomodulation therapy accelerates soft tissue regeneration and bone formation.


Asunto(s)
Proceso Alveolar/fisiopatología , Proceso Alveolar/efectos de la radiación , Regeneración Ósea/efectos de la radiación , Rayos Láser , Adulto , Tejido Conectivo/patología , Tejido Conectivo/efectos de la radiación , Epitelio/patología , Epitelio/efectos de la radiación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteogénesis/efectos de la radiación , Adulto Joven
17.
Int J Radiat Biol ; 94(12): 1116-1124, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-30359158

RESUMEN

PURPOSE: Epidemiological evidence regarding the radiosensitivity of the lens of the eye and radiation cataract development has led to changes in the EU Basic Safety Standards for protection of the lens against ionizing radiation. However, mechanistic details of lens radiation response pathways and their significance for cataractogenesis remain unclear. Radiation-induced DNA damage and the potential impairment of repair pathways within the lens epithelium, a cell monolayer that covers the anterior hemisphere of the lens, are likely to be involved. MATERIALS AND METHODS: In this work, the lens epithelium has been analyzed for its DNA double-strand break (DSB) repair response to ionizing radiation. The responses of epithelial cells located at the anterior pole (central region) have been compared to at the very periphery of the monolayer (germinative and transitional zones). Described here are the different responses in the two regions and across four strains (C57BL/6, 129S2, BALB/c and CBA/Ca) over a low dose (0-25 mGy) in-vivo whole body X-irradiation range up to 24 hours post exposure. RESULTS: DNA damage and repair as visualized through 53BP1 staining was present across the lens epithelium, although repair kinetics appeared non-uniform. Epithelial cells in the central region have significantly more 53BP1 foci. The sensitivities of different mouse strains have also been compared. CONCLUSIONS: 129S2 and BALB/c showed higher levels of DNA damage, with BALB/c showing significantly less inter-individual variability and appearing to be a more robust model for future DNA damage and repair studies. As a result of this study, BALB/c was identified as a suitable radiosensitive lens strain to detect and quantify early low dose ionizing radiation DNA damage effects in the mouse eye lens specifically, as an indicator of cataract formation.


Asunto(s)
Daño del ADN , Cristalino/metabolismo , Cristalino/efectos de la radiación , Animales , Reparación del ADN/efectos de la radiación , Relación Dosis-Respuesta en la Radiación , Epitelio/metabolismo , Epitelio/efectos de la radiación , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Tolerancia a Radiación/genética , Especificidad de la Especie , Factores de Tiempo
18.
Sci Rep ; 8(1): 13754, 2018 09 13.
Artículo en Inglés | MEDLINE | ID: mdl-30213992

RESUMEN

Adequate and rapid mucosal regeneration is one of the most important factors in the healing process of nasal mucosa after surgery or trauma. In particular, delayed mucosal regeneration after surgery is an important cause of surgical failure. However, no effective treatment is available yet. Non-thermal plasma (NTP) has several medical effects, but the existing probe type is limited to local direct treatment. Therefore, we investigated the various effects using liquid type plasma to overcome this limitation. In addition, the therapeutic effects of non-thermal plasma treated solution (NTS) on nasal mucosa have yet to be determined. Experiments were carried out using BEAS-2B, a human bronchial epithelial cell line similar to nasal mucosa epithelium. NTS had no cytotoxicity to the BEAS-2B cells and enhanced cell proliferation. NTS also promoted migration of BEAS-2B cells. NTS increased cell proliferation and migration via epidermal growth factor receptor (EGFR) activities and epithelial-to-mesenchymal transition (EMT) signaling. Furthermore, NTS enhanced wound healing of nasal mucosa in an animal model. Accordingly, NTS promotes nasal mucosa wound healing by increasing cell proliferation and migration. These findings suggest the therapeutic potential of NTS in nasal mucosa wound healing.


Asunto(s)
Proliferación Celular/efectos de la radiación , Mucosa Nasal/fisiopatología , Gases em Plasma , Regeneración , Animales , Bronquios/patología , Bronquios/efectos de la radiación , Movimiento Celular/efectos de la radiación , Modelos Animales de Enfermedad , Células Epiteliales/patología , Células Epiteliales/efectos de la radiación , Transición Epitelial-Mesenquimal/efectos de la radiación , Epitelio/patología , Epitelio/efectos de la radiación , Genes erbB-1/genética , Humanos , Mucosa Nasal/efectos de la radiación , Mucosa Nasal/cirugía , Ratas , Transducción de Señal/efectos de la radiación , Cicatrización de Heridas/efectos de la radiación
19.
Int J Radiat Biol ; 94(11): 967-974, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30265181

RESUMEN

PURPOSE: The most exposed tissue upon radon exposure is the bronchial epithelium where goblet cells serve as responsive and adaptable front-line defenders. They can rapidly produce a vast amount of mucus, and can change in number, in response to airway insults. The objective of the present study is to quantify the effects of mucus discharge and goblet cell hyperplasia on the microscopic dose consequences of macroscopic radon exposures. METHODS: For this purpose, computational models of the bronchial epithelium and alpha-particle transport have been prepared and applied to quantify the hits received and doses absorbed by cell nuclei in case of different mucus thicknesses and goblet cell number. RESULTS AND CONCLUSIONS: Both mucus discharge and induction of goblet cell hyperplasia reduce radiation burden at the cellular level, and as such they both can be considered as radioadaptive responses to radon exposure. As compared to basal cell hyperplasia, goblet cell hyperplasia is more effective in reducing the microscopic dose consequences of a given macroscopic exposure. Such changes in exposure geometry highlight the need for improvements in the application of biokinetic and dosimetry models for incorporated radionuclides as well as the dose and dose rate effectiveness factor.


Asunto(s)
Bronquios/citología , Bronquios/efectos de la radiación , Células Caliciformes/patología , Células Caliciformes/efectos de la radiación , Moco/metabolismo , Moco/efectos de la radiación , Radón/efectos adversos , Epitelio/efectos de la radiación , Hiperplasia/patología , Radiometría
20.
Arch Oral Biol ; 94: 62-68, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29979974

RESUMEN

OBJECTIVES: Wound healing of the oral mucosal epithelium through the application of far infrared radiation emitted by isotropic high-density carbon was investigated in order to clarify the preventive and therapeutic effects of isotropic high-density carbon on oral mucosal injury. MATERIALS AND METHODS: A carbon massager with an isotropic high-density carbon tip was used. Far infrared radiation was applied to the human buccal mucosal squamous cell carcinoma cell line, HO-1-N-1 using a carbon massager, and cell growth factors and heat shock protein levels were measured using real-time RT-PCR and ELISA. Far infrared radiation was applied to oral mucosal injury in SD rats over time using the carbon massager, and its effects were examined by HE staining and immunostaining. The immunostaining positive rate was measured and analyzed using image analysis software. RESULTS: Far infrared radiation induced stronger mRNA expression and higher HSP27 and HSP70 protein levels on real-time RT-PCR and ELISA than in the control group. The far infrared radiation of oral mucosal injury in rats induced strong positive reactions, and positive rates for Ki67, HSP27, and HSP70 were higher than those in the control group. CONCLUSIONS: The treatment of oral mucosal injury with far infrared radiation emitted by isotropic high-density carbon appears to have promoted heat shock protein production and induced regenerative reactions more strongly than in the control group.


Asunto(s)
Carbono/análisis , Rayos Infrarrojos/efectos adversos , Mucosa Bucal/patología , Mucosa Bucal/efectos de la radiación , Cicatrización de Heridas/efectos de la radiación , Animales , Carcinoma de Células Escamosas/radioterapia , Línea Celular Tumoral/efectos de la radiación , Epitelio/lesiones , Epitelio/patología , Epitelio/efectos de la radiación , Fibrosis/patología , Proteínas de Choque Térmico HSP27/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas de Choque Térmico/análisis , Proteínas de Choque Térmico/genética , Humanos , Péptidos y Proteínas de Señalización Intercelular/análisis , Péptidos y Proteínas de Señalización Intercelular/genética , Antígeno Ki-67/metabolismo , Masculino , Mucosa Bucal/lesiones , Neoplasias de la Boca/radioterapia , ARN Mensajero/metabolismo , Ratas
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