RESUMEN
Salivary gland homeostasis and regeneration after radiotherapy depend significantly on progenitor cells. However, the lineage of submandibular gland (SMG) progenitor cells remains less defined compared with other normal organs. Here, using a mouse strain expressing regulated CreERT2 recombinase from the endogenous Tert locus, we identify a distinct telomerase-expressing (TertHigh) cell population located in the ductal region of the adult SMG. These TertHigh cells contribute to ductal cell generation during SMG homeostasis and to both ductal and acinar cell renewal 1 year after radiotherapy. TertHigh cells maintain self-renewal capacity during in vitro culture, exhibit resistance to radiation damage, and demonstrate enhanced proliferative activity after radiation exposure. Similarly, primary human SMG cells with high Tert expression display enhanced cell survival after radiotherapy, and CRISPR-activated Tert in human SMG spheres increases proliferation after radiation. RNA sequencing reveals upregulation of "cell cycling" and "oxidative stress response" pathways in TertHigh cells following radiation. Mechanistically, Tert appears to modulate cell survival through ROS levels in SMG spheres following radiation damage. Our findings highlight the significance of TertHigh cells in salivary gland biology, providing insights into their response to radiotherapy and into their use as a potential target for enhancing salivary gland regeneration after radiotherapy.
Asunto(s)
Homeostasis , Regeneración , Telomerasa , Telomerasa/metabolismo , Telomerasa/genética , Animales , Homeostasis/genética , Homeostasis/efectos de la radiación , Ratones , Regeneración/efectos de la radiación , Regeneración/genética , Humanos , Glándulas Salivales/efectos de la radiación , Glándulas Salivales/metabolismo , Glándulas Salivales/citología , Proliferación Celular/efectos de la radiación , Proliferación Celular/genética , Supervivencia Celular/efectos de la radiación , Supervivencia Celular/genética , Glándula Submandibular/efectos de la radiación , Glándula Submandibular/metabolismo , Células Madre/efectos de la radiación , Células Madre/metabolismo , Células Madre/citología , Radioterapia/efectos adversos , Especies Reactivas de Oxígeno/metabolismo , Células CultivadasRESUMEN
BACKGROUND: Antimicrobial blue light (aBL) kills a variety of bacteria, including Porphyromonas gingivalis. However, little is known about the transcriptomic response of P. gingivalis to aBL therapy. This study was designed to evaluate the selective cytotoxicity of aBL against P. gingivalis over human cells and to further investigate the genetic response of P. gingivalis to aBL at the transcriptome level. METHODS: Colony forming unit (CFU) testing, confocal laser scanning microscopy (CLSM), and scanning electron microscopy (SEM) were used to investigate the antimicrobial effectiveness of blue light against P. gingivalis. The temperatures of the irradiated targets were measured to prevent overheating. Multiple fluorescent probes were used to quantify reactive oxygen species (ROS) generation after blue-light irradiation. RNA sequencing (RNA-seq) was used to investigate the changes in global gene expression. Following the screening of target genes, real-time quantitative polymerase chain reaction (RT-qPCR) was performed to confirm the regulation of gene expression. RESULTS: A 405 nm aBL at 100 mW/cm2 significantly killed P. gingivalis within 5 min while sparing human gingival fibroblasts (HGFs). No obvious temperature changes were detected in the irradiated surface under our experimental conditions. RNA-seq showed that the transcription of multiple genes was regulated, and RT-qPCR revealed that the expression levels of the genes RgpA and RgpB, which may promote heme uptake, as well as the genes Ftn and FetB, which are related to iron homeostasis, were significantly upregulated. The expression levels of the FeoB-2 and HmuR genes, which are related to hydroxyl radical scavenging, were significantly downregulated. CONCLUSIONS: aBL strengthens the heme uptake and iron export gene pathways while reducing the ROS scavenging pathways in P. gingivalis, thus improving the accumulation of endogenous photosensitizers and enhancing oxidative damage to P. gingivalis.
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Color , Regulación Bacteriana de la Expresión Génica , Genes Bacterianos , Hierro , Luz , Porfirinas , Porphyromonas gingivalis , Porfirinas/metabolismo , Hierro/metabolismo , Porphyromonas gingivalis/citología , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/metabolismo , Porphyromonas gingivalis/efectos de la radiación , Transporte Biológico/genética , Transporte Biológico/efectos de la radiación , Humanos , Encía/citología , Fibroblastos/citología , Fibroblastos/efectos de la radiación , Radical Hidroxilo/metabolismo , Hemo/metabolismo , Regulación hacia Arriba/efectos de la radiación , Homeostasis/efectos de la radiación , Regulación hacia Abajo/efectos de la radiación , Viabilidad Microbiana/efectos de la radiación , Especies Reactivas de Oxígeno/metabolismo , Aerobiosis , Genes Bacterianos/efectos de la radiación , Regulación Bacteriana de la Expresión Génica/genética , Regulación Bacteriana de la Expresión Génica/efectos de la radiaciónRESUMEN
Obesity and mobile phone usage have simultaneously spread worldwide. Radio frequency-modulated electromagnetic fields (RF-EMFs) emitted by mobile phones are largely absorbed by the head of the user, influence cerebral glucose metabolism, and modulate neuronal excitability. Body weight adjustment, in turn, is one of the main brain functions as food intake behavior and appetite perception underlie hypothalamic regulation. Against this background, we questioned if mobile phone radiation and food intake may be related. In a single-blind, sham-controlled, randomized crossover comparison, 15 normal-weight young men (23.47 ± 0.68 years) were exposed to 25 min of RF-EMFs emitted by two different mobile phone types vs. sham radiation under fasting conditions. Spontaneous food intake was assessed by an ad libitum standard buffet test and cerebral energy homeostasis was monitored by 31phosphorus-magnetic resonance spectroscopy measurements. Exposure to both mobile phones strikingly increased overall caloric intake by 22-27% compared with the sham condition. Differential analyses of macronutrient ingestion revealed that higher calorie consumption was mainly due to enhanced carbohydrate intake. Measurements of the cerebral energy content, i.e., adenosine triphosphate and phosphocreatine ratios to inorganic phosphate, displayed an increase upon mobile phone radiation. Our results identify RF-EMFs as a potential contributing factor to overeating, which underlies the obesity epidemic. Beyond that, the observed RF-EMFs-induced alterations of the brain energy homeostasis may put our data into a broader context because a balanced brain energy homeostasis is of fundamental importance for all brain functions. Potential disturbances by electromagnetic fields may therefore exert some generalized neurobiological effects, which are not yet foreseeable.
Asunto(s)
Teléfono Celular , Ingestión de Alimentos/efectos de la radiación , Radiación Electromagnética , Metabolismo Energético/efectos de la radiación , Homeostasis/efectos de la radiación , Encéfalo/efectos de la radiación , Estudios Cruzados , Ingestión de Energía/efectos de la radiación , Humanos , Masculino , Método Simple Ciego , Adulto JovenRESUMEN
Human epidermal melanocytes play a central role in sensing the environment and protecting the skin from the drastic effects of solar ultraviolet radiation and other environmental toxins or inflammatory agents. Melanocytes survive in the epidermis for decades, which subjects them to chronic environmental insults. Melanocytes have a poor self-renewal capacity; therefore, it is critical to ensure their survival with genomic stability. The function and survival of melanocytes is regulated by an elaborate network of paracrine factors synthesized mainly by epidermal keratinocytes and dermal fibroblasts. A symbiotic relationship exists between epidermal melanocytes and keratinocytes on the one hand, and between melanocytes and dermal fibroblasts on the other hand. Melanocytes protect epidermal keratinocytes and dermal fibroblasts from the damaging effects of solar radiation, and the latter cells synthesize biochemical mediators that maintain the homeostasis, and regulate the stress response of melanocytes. Disruption of the paracrine network results in pigmentary disorders, due to abnormal regulation of melanin synthesis, and compromise of melanocyte survival or genomic stability. This review provides an update of the current knowledge of keratinocyte- and fibroblast-derived paracrine factors and their contribution to melanocyte physiology, and how their abnormal production is involved in the pathogenesis of common pigmentary disorders.
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Fibroblastos/metabolismo , Homeostasis , Queratinocitos/metabolismo , Melanocitos/metabolismo , Trastornos de la Pigmentación/patología , Rayos Ultravioleta , Animales , Fibroblastos/efectos de la radiación , Homeostasis/efectos de la radiación , Humanos , Queratinocitos/efectos de la radiación , Melanocitos/efectos de la radiaciónRESUMEN
The main difficulty of radiotherapy is to destroy cancer cells without depletion of healthy tissue [...].
Asunto(s)
Radiación , Células Madre/efectos de la radiación , Células Madre Adultas/efectos de la radiación , Tratamiento Basado en Trasplante de Células y Tejidos , Homeostasis/efectos de la radiación , Humanos , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/efectos de la radiación , Organoides/efectos de la radiaciónRESUMEN
Phototropins are plasma membrane-associated photoreceptors of blue light and UV-A/B radiation. The Arabidopsis thaliana genome encodes two phototropins, PHOT1 and PHOT2, that mediate phototropism, chloroplast positioning, and stomatal opening. They are well characterized in terms of photomorphogenetic processes, but so far, little was known about their involvement in photosynthesis, oxidative stress responses, and cell death. By analyzing phot1, phot2 single, and phot1phot2 double mutants, we demonstrated that both phototropins influence the photochemical and non-photochemical reactions, photosynthetic pigments composition, stomata conductance, and water-use efficiency. After oxidative stress caused by UV-C treatment, phot1 and phot2 single and double mutants showed a significantly reduced accumulation of H2O2 and more efficient photosynthetic electron transport compared to the wild type. However, all phot mutants exhibited higher levels of cell death four days after UV-C treatment, as well as deregulated gene expression. Taken together, our results reveal that on the one hand, both phot1 and phot2 contribute to the inhibition of UV-C-induced foliar cell death, but on the other hand, they also contribute to the maintenance of foliar H2O2 levels and optimal intensity of photochemical reactions and non-photochemical quenching after an exposure to UV-C stress. Our data indicate a novel role for phototropins in the condition-dependent optimization of photosynthesis, growth, and water-use efficiency as well as oxidative stress and cell death response after UV-C exposure.
Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiología , Arabidopsis/efectos de la radiación , Estrés Oxidativo/efectos de la radiación , Fotosíntesis/efectos de la radiación , Proteínas Serina-Treonina Quinasas/metabolismo , Rayos Ultravioleta , Antioxidantes/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Biomasa , Muerte Celular/efectos de la radiación , Fluorescencia , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Homeostasis/efectos de la radiación , Peróxido de Hidrógeno/metabolismo , Mutación/genética , Estrés Oxidativo/genética , Pigmentos Biológicos/metabolismo , Hojas de la Planta/anatomía & histología , Hojas de la Planta/efectos de la radiación , Estomas de Plantas/fisiología , Estomas de Plantas/efectos de la radiación , Proteínas Serina-Treonina Quinasas/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transcriptoma/genética , Transcriptoma/efectos de la radiación , AguaRESUMEN
DNA damage causes cancer, impairs development and accelerates aging. Transcription-blocking lesions and transcription-coupled repair defects lead to developmental failure and premature aging in humans. Following DNA repair, homeostatic processes need to be reestablished to ensure development and maintain tissue functionality. Here, we report that, in Caenorhabditis elegans, removal of the WRAD complex of the MLL/COMPASS H3K4 methyltransferase exacerbates developmental growth retardation and accelerates aging, while depletion of the H3K4 demethylases SPR-5 and AMX-1 promotes developmental growth and extends lifespan amid ultraviolet-induced damage. We demonstrate that DNA-damage-induced H3K4me2 is associated with the activation of genes regulating RNA transport, splicing, ribosome biogenesis and protein homeostasis and regulates the recovery of protein biosynthesis that ensures survival following genotoxic stress. Our study uncovers a role for H3K4me2 in coordinating the recovery of protein biosynthesis and homeostasis required for developmental growth and longevity after DNA damage.
Asunto(s)
Caenorhabditis elegans/genética , Reparación del ADN , ADN de Helmintos/genética , Regulación del Desarrollo de la Expresión Génica , Histonas/genética , Animales , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efectos de la radiación , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Tamaño de la Nidada/efectos de la radiación , Daño del ADN , Reparación del ADN/efectos de la radiación , ADN de Helmintos/metabolismo , Histonas/antagonistas & inhibidores , Histonas/metabolismo , Homeostasis/efectos de la radiación , Longevidad/efectos de la radiación , Oxidorreductasas N-Desmetilantes/genética , Oxidorreductasas N-Desmetilantes/metabolismo , Biosíntesis de Proteínas/efectos de la radiación , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Rayos UltravioletaRESUMEN
BACKGROUND: The primary objective of this study was to investigate the effect of low dose ionizing radiation exposure on thiol/disulfide homeostasis and ischemia modified albumin levels. The secondary objective is to compare thiol/disulfide homeostasis and ischemia modified albumin levels among the personnel exposed to low dose ionizing radiation in anesthesia application areas, in and out of the Operation room. METHODS: The study included a total of 90 volunteers aged between 18 and 65 years old, with 45 personnel working in a setting with potential for radiation exposure (Exposed Group) and 45 personnel in a setting without radiation exposure (Control Group). Their native thiol, total thiol, disulphide, albumine and IMA levels were measured. Exposed group included personnel who were exposed to radiation outside the operating room - Operation room (-) Group and inside the Operating room - Operation room (+) Group. RESULTS: Albumin, native and total thiol levels were significantly lower in the participants exposed to radiation in the anesthesia application area, no statistically significant difference was found in terms of disulfide and ischemia modified albumin levels. In the Operation room (-) group exposed to radiation, native thiol and total thiol values were significantly lower compared to the Operation room (+) groups. CONCLUSION: Awareness of being in danger of oxidative stress should be established in personnel exposed to radiation in the anesthesia application area following low dose ionizing radiation exposure, and the necessary measures should be taken.
Asunto(s)
Disulfuros/sangre , Disulfuros/efectos de la radiación , Homeostasis/efectos de la radiación , Exposición Profesional , Dosis de Radiación , Exposición a la Radiación , Radiación Ionizante , Albúmina Sérica Humana/efectos de la radiación , Compuestos de Sulfhidrilo/sangre , Compuestos de Sulfhidrilo/efectos de la radiación , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Quirófanos , Estudios Prospectivos , Adulto JovenRESUMEN
Abstract Background: The primary objective of this study was to investigate the effect of low dose ionizing radiation exposure on thiol/disulfide homeostasis and ischemia modified albumin levels. The secondary objective is to compare thiol/disulfide homeostasis and ischemia modified albumin levels among the personnel exposed to low dose ionizing radiation in anesthesia application areas, in and out of the operation room. Methods: The study included a total of 90 volunteers aged between 18 and 65 years old, with 45 personnel working in a setting with potential for radiation exposure (Exposed Group) and 45 personnel in a setting without radiation exposure (Control Group). Their native thiol, total thiol, disulphide, albumine and IMA levels were measured. Exposed group included personnel who were exposed to radiation outside the operating room - Operation room (−) Group and inside the operating room - Operation room (+) Group. Results: Albumin, native and total thiol levels were significantly lower in the participants exposed to radiation in the anesthesia application area; no statistically significant difference was found in terms of disulfide and ischemia modified albumin levels. In the Operation room (−) Group exposed to radiation, native thiol and total thiol values were significantly lower compared to the Operation room (+) Group. Conclusion: Awareness of being in danger of oxidative stress should be established in personnel exposed to radiation in the anesthesia application area following low dose ionizing radiation exposure, and the necessary measures should be taken.
Resumo Justificativa: O objetivo principal do estudo foi investigar o efeito de exposição à radiação ionizante de baixa dose nos níveis de homeostase tiol/dissulfeto e de albumina modificada por isquemia. O objetivo secundário foi comparar os níveis de homeostase tiol/dissulfeto e albumina modificada por isquemia entre indivíduos expostos à radiação ionizante de baixa dose nas áreas de procedimentos anestésicos, dentro e fora da sala de cirurgia. Método: O estudo incluiu um total de 90 voluntários com idades entre 18 e 65 anos, 45 profissionais que trabalhavam em ambiente de exposição potencial a radiação (Grupo Exposto) e 45 profissionais que trabalhavam em ambiente sem exposição à radiação (Grupo Controle). Foram medidos os níveis de tiol nativo, tiol total, dissulfeto, albumina e albumina modificada por isquemia. O Grupo Exposto era constituído por profissionais expostos a radiação fora da sala de cirurgia - Grupo sala de cirurgia (-) e na sala de cirurgia - Grupo sala de cirurgia (+). Resultados: Os níveis de albumina, tiol nativo e total foram significantemente mais baixos nos participantes expostos à radiação em área de realização de anestesia, e nenhuma diferença estatisticamente significante foi encontrada para os níveis de dissulfeto e albumina modificada por isquemia. No Grupo exposto sala de cirurgia (-), os valores de tiol nativo e tiol total foram significantemente mais baixos quando comparados ao Grupo sala de cirurgia (+). Conclusões: Os profissionais expostos à radiação em área de realização de anestesia devem ser conscientizados quanto ao perigo do estresse oxidativo após exposição à radiação ionizante de baixa dose e medidas cabíveis devem ser instituídas.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Anciano , Adulto Joven , Dosis de Radiación , Radiación Ionizante , Compuestos de Sulfhidrilo/efectos de la radiación , Compuestos de Sulfhidrilo/sangre , Exposición Profesional , Exposición a la Radiación , Disulfuros/efectos de la radiación , Disulfuros/sangre , Albúmina Sérica Humana/efectos de la radiación , Homeostasis/efectos de la radiación , Quirófanos , Biomarcadores/sangre , Estudios Prospectivos , Persona de Mediana EdadRESUMEN
Although an electrohypersensitivity (EHS) is reported in numerous studies, some authors associate hyperfrequencies (HF)-related pains with a nocebo effect while others suggest a biological effect. Therefore, we aimed to suggest hypotheses about the complex mechanisms of headaches related to HF-exposure. We crossed basic features of headaches with relevant studies (from the year 2000 up to 2018) emphasizing on the HF effects that may lead to pain genesis: neuroglial dysmetabolism, neuroinflammation, changes in cerebral blood perfusion, blood-brain barrier dysfunction and electrophysiological evidences of hyperexcitability. We privileged studies implying a sham exposure (for in vivo studies) and a specific absorption rate lower than 4 W/Kg. HF-induced headaches may involve an indirect inflammatory process (neurogenic, magnetogenic or thermogenic) as well as a direct biophysical effect (thermogenic or magnetogenic). We linked inflammatory processes to meningeal dysperfusion or primary neuroglial dysfunction triggered by non-thermal irradiation or HF-induced heating at thermal powers. In the latter case, HF-induced excitoxicity and oxidative stress probably play a crucial role. Such disorders may lead to vascular-trigeminal activation in predisposed people. Interestingly, an abnormal oxidative stress predisposition had been demonstrated in overall 80% of EHS self-reporting patients. In the case of direct effects, pain pathways' activation may be directly triggered by HF-irradiation (heating and/or transcranial HF-induced ectopic action potentials). Further research on HF-related headaches is needed.
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Cefalea/etiología , Microondas/efectos adversos , Barrera Hematoencefálica/metabolismo , Barrera Hematoencefálica/efectos de la radiación , Cefalea/metabolismo , Cefalea/fisiopatología , Homeostasis/efectos de la radiación , Humanos , Permeabilidad/efectos de la radiaciónRESUMEN
Glaucoma is the leading cause of irreversible vision loss. Ocular hypertension is a major risk factor for glaucoma and recent work has demonstrated critical early neuroinflammatory insults occur in the optic nerve head following ocular hypertension. Microglia and infiltrating monocytes are likely candidates to drive these neuroinflammatory insults. However, the exact molecular identity / transcriptomic profile of microglia following ocular hypertensive insults is unknown. To elucidate the molecular identity of microglia after long-term exposure to ocular hypertension, we used a mouse model of glaucoma (DBA/2 J). We performed RNA-sequencing of microglia mRNA from the optic nerve head at a time point following ocular hypertensive insults, but preceding detectable neurodegeneration (with microglia identified as being CD45lo/CD11b+/CD11c-). Furthermore, RNA-sequencing was performed on optic nerve head microglia from mice treated with radiation therapy, a potent therapy preventing neuroinflammatory insults. Transcriptomic profiling of optic nerve head microglia mRNA identifies metabolic priming with marked changes in mitochondrial gene expression, and changes to phagocytosis, inflammatory, and sensome pathways. The data predict that many functions of microglia that help maintain tissue homeostasis are affected. Comparative analysis of these data with data from previously published whole optic nerve head tissue or monocyte-only samples from DBA/2 J mice demonstrate that many of the neuroinflammatory signatures in these data sets arise from infiltrating monocytes and not reactive microglia. Finally, our data demonstrate that prophylactic radiation therapy of DBA/2 J mice potently abolishes these microglia metabolic transcriptomic changes at the same time points. Together, our data provide a unique resource for the community to help drive further hypothesis generation and testing in glaucoma.
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Regulación de la Expresión Génica , Homeostasis/genética , Microglía/metabolismo , Microglía/patología , Hipertensión Ocular/genética , Hipertensión Ocular/patología , Disco Óptico/metabolismo , Animales , Regulación hacia Abajo/genética , Femenino , Regulación de la Expresión Génica/efectos de la radiación , Homeostasis/efectos de la radiación , Presión Intraocular/genética , Presión Intraocular/efectos de la radiación , Ratones Endogámicos DBA , Microglía/efectos de la radiación , Monocitos/metabolismo , Monocitos/patología , Hipertensión Ocular/fisiopatología , Disco Óptico/patología , Disco Óptico/efectos de la radiación , Fagocitosis/genética , Fenotipo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Transcriptoma/genética , Regulación hacia Arriba/genéticaRESUMEN
CalbindinD28K (Calb1) may protect human lens epithelial cells (HLECs) from apoptosis, which is a process resulting in individual cell death. The protective effects of Calb1 may be attributed to buffering high concentrations of Ca2+. The present study investigated the mechanisms through which Calb1 protects SRA01/04 cells (a human lens epithelial cell line) against apoptosis induced by ultraviolet B (UVB) exposure. Cells transfected with a lentivirus overexpressing Calb1 and control cells were treated with 40 µW/cm2 irradiation for 15 min and then cultured for 24 h. The changes in intracellular Ca2+ were detected by colorimetry, and the protein expression levels of Bad, Bcl2 and caspase12 were measured by western blot analysis. The intracellular Ca2+ concentration of control HLECs increased significantly following UVB irradiation, whereas in Calb1overexpressing cells, the Ca2+ levels remained steady. In the control cells, the expression of Bad and caspase12 was upregulated, and that of Bcl2 was downregulated. Notably, during UVB radiationinduced apoptosis, the overexpression of Calb1 inhibited cell death, resulting in the decreased expression of Bad and caspase12, and in the upregulated expression of Bcl2. These results suggested that Calb1 inhibited the upregulation of genes involved in apoptosis. The siRNAmediated knockdown of Calb1 resulted in increased rates of UVB radiationinduced apoptosis, the increased expression of Bad and caspase12, and the decreased expression of Bcl2, further demonstrating that Calb1 may mediate UVB radiationmediated apoptosis by regulating Ca2+. On the whole, the findings of the present study indicate that UVB exposure can lead to an imbalance in the intracellular Ca2+ homeostasis in HLECs and that Calb1 protein exerts a negative effect on the expression of proapoptotic genes in HLECs. Calb1 may thus inhibit the UVB radiationinduced apoptosis of HLECs by regulating Ca2+.
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Apoptosis/fisiología , Calbindina 1/metabolismo , Células Epiteliales/metabolismo , Rayos Ultravioleta/efectos adversos , Apoptosis/efectos de la radiación , Calcio/metabolismo , Caspasa 12/metabolismo , Línea Celular , Células Epiteliales/efectos de la radiación , Homeostasis/fisiología , Homeostasis/efectos de la radiación , Humanos , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Regulación hacia Arriba/fisiología , Regulación hacia Arriba/efectos de la radiación , Proteína Letal Asociada a bcl/metabolismoRESUMEN
BACKGROUND: Burn wound healing is delayed due to several critical factors such as sustained inflammation, vascular disorder, neuropathy, enhanced proteolysis, infection, and oxidative stress. Burn wounds have limited oxygen supply owing to compromised blood circulation. Hypoxic burn milieu leads to free radicals overproduction incurring oxidative injury, which impedes repair process causing damage to cell membranes, proteins, lipids, and DNA. Photobiomodulation (PBM) with 904 nm superpulsed laser had shown potent healing efficacy via attenuating inflammation while enhancing proliferation, angiogenesis, collagen accumulation, and bioenergetic activation in burn wounds. METHODS: This study investigated the effects of 904 nm superpulsed laser at 0.4 mW/cm2 average power density, 0.2 J/cm2 total energy density, 100 Hz frequency, and 200 ns pulse width for 10 min daily for seven days postburn injury on nitroxidative stress, endogenous antioxidants status, and redox homeostasis. RESULTS: Photobiomodulation treatment significantly decreased reactive oxygen species, nitric oxide, and lipid peroxidation levels as compared to non-irradiated control. Further, protective action of PBM against protein oxidative damage was evidenced by reduced protein carbonylation and advanced oxidation protein product levels along with significantly enhanced endogenous antioxidants levels of SOD, catalase, GPx, GST, reduced glutathione, and thiol (T-SH, Np-SH, P-SH). Biochemical changes aid in reduction of oxidative stress and maintenance of redox homeostasis, which further well corroborated by significantly up-regulated protein expression of Nrf 2, hemeoxygenase (HO-1), and thioredoxin reductase 2 (Txnrd2). CONCLUSION: Photobiomodulation with 904 nm superpulsed laser led to reduction of nitroxidative stress, induction of endogenous antioxidants, and maintenance of redox homeostasis that could play a vital role in augmentation of burn wound healing.
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Quemaduras/fisiopatología , Quemaduras/radioterapia , Láseres de Semiconductores/uso terapéutico , Terapia por Luz de Baja Intensidad , Estrés Oxidativo/efectos de la radiación , Cicatrización de Heridas , Productos Avanzados de Oxidación de Proteínas/metabolismo , Animales , Catalasa/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Glutatión Transferasa/metabolismo , Hemo Oxigenasa (Desciclizante)/metabolismo , Homeostasis/efectos de la radiación , Masculino , Malondialdehído/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Óxido Nítrico/metabolismo , Oxidación-Reducción/efectos de la radiación , Carbonilación Proteica/efectos de la radiación , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Superóxido Dismutasa/metabolismo , Tiorredoxina Reductasa 2/metabolismoRESUMEN
Dim light at night (dLAN) has become a pervasive part of the modern world, and growing evidence shows its association with increased health risks. Though this link is attributed to a disturbed circadian clock, the underlying mechanisms that can explain how circadian disruption from dLAN causes negative health effects remain unclear. Here, we exposed rats to a light-dark cycle (12:12 h) with low-intensity light at night (~2 lx) for 2 and 5 weeks and explored the steady-state pattern of circulating immune cells and renal immune-related markers, which are well controlled by the circadian clock. After 5 weeks, dLAN impaired the daily variation in several types of white blood cells, especially monocytes and T cells. Two-week dLAN caused a reduction in blood monocytes and altered gene expression of macrophage marker Cd68 and monocyte-attracting chemokine Ccl2 in the kidney. Interestingly, dLAN decreased renal 3-nitrotyrosine levels and resulted in up-regulation of the main endogenous antioxidant pathways, indicating a disturbance in the renal redox balance and an activation of compensatory mechanisms. These effects paralleled the altered renal expression of the molecular clock components and increased plasma corticosterone levels. Together, our results show that chronic exposure to dLAN weakened the circadian control of daily variation of circulating immune cells and disturbed renal immune and redox homeostasis. Consequences of this dLAN-disturbed immune balance on the ability of the immune system to cope with other challenges should by clarified in further studies.
Asunto(s)
Ritmo Circadiano/inmunología , Sistema Inmunológico/efectos de la radiación , Riñón/inmunología , Luz/efectos adversos , Fotoperiodo , Animales , Antígenos CD/biosíntesis , Antígenos CD/genética , Antígenos de Diferenciación Mielomonocítica/biosíntesis , Antígenos de Diferenciación Mielomonocítica/genética , Proteínas CLOCK/biosíntesis , Proteínas CLOCK/genética , Moléculas de Adhesión Celular/biosíntesis , Moléculas de Adhesión Celular/genética , Quimiocinas/biosíntesis , Quimiocinas/genética , Corticosterona/sangre , Regulación de la Expresión Génica/efectos de la radiación , Homeostasis/efectos de la radiación , Inmunofenotipificación , Riñón/metabolismo , Corteza Renal/enzimología , Recuento de Leucocitos , Masculino , Melatonina/sangre , Oxidación-Reducción , Ratas , Ratas Wistar , Estallido Respiratorio , Superóxido Dismutasa/análisisRESUMEN
Group 3 innate lymphoid cells (ILC3s) are major regulators of inflammation, infection, microbiota composition and metabolism1. ILC3s and neuronal cells have been shown to interact at discrete mucosal locations to steer mucosal defence2,3. Nevertheless, it is unclear whether neuroimmune circuits operate at an organismal level, integrating extrinsic environmental signals to orchestrate ILC3 responses. Here we show that light-entrained and brain-tuned circadian circuits regulate enteric ILC3s, intestinal homeostasis, gut defence and host lipid metabolism in mice. We found that enteric ILC3s display circadian expression of clock genes and ILC3-related transcription factors. ILC3-autonomous ablation of the circadian regulator Arntl led to disrupted gut ILC3 homeostasis, impaired epithelial reactivity, a deregulated microbiome, increased susceptibility to bowel infection and disrupted lipid metabolism. Loss of ILC3-intrinsic Arntl shaped the gut 'postcode receptors' of ILC3s. Strikingly, light-dark cycles, feeding rhythms and microbial cues differentially regulated ILC3 clocks, with light signals being the major entraining cues of ILC3s. Accordingly, surgically or genetically induced deregulation of brain rhythmicity led to disrupted circadian ILC3 oscillations, a deregulated microbiome and altered lipid metabolism. Our work reveals a circadian circuitry that translates environmental light cues into enteric ILC3s, shaping intestinal health, metabolism and organismal homeostasis.
Asunto(s)
Encéfalo/efectos de la radiación , Ritmo Circadiano/efectos de la radiación , Homeostasis/efectos de la radiación , Intestinos/inmunología , Intestinos/efectos de la radiación , Luz , Linfocitos/inmunología , Linfocitos/efectos de la radiación , Factores de Transcripción ARNTL/deficiencia , Factores de Transcripción ARNTL/genética , Factores de Transcripción ARNTL/metabolismo , Animales , Relojes Biológicos/genética , Relojes Biológicos/efectos de la radiación , Encéfalo/fisiología , Ritmo Circadiano/genética , Ritmo Circadiano/inmunología , Ritmo Circadiano/fisiología , Señales (Psicología) , Conducta Alimentaria/efectos de la radiación , Femenino , Microbioma Gastrointestinal/efectos de la radiación , Inmunidad Innata/efectos de la radiación , Intestinos/citología , Metabolismo de los Lípidos , Linfocitos/metabolismo , Masculino , Ratones , FotoperiodoRESUMEN
Photobiomodulation relies on the transfer of energy from incident photons to a cell photoacceptor. For many years the concept of photobiomodulation and its outcome has been based upon a belief that the sole receptor within the cell was the mitochondrion. Recently, it has become apparent that there are other photoacceptors operating in different regions of the electromagnetic spectrum. Alternative photoacceptors would appear to be water and mechanisms regulating calcium homeostasis, despite a direct effect of laser photonic energy on intracellular calcium concentration outwith mitochondrial activity or influence, have not been clearly demonstrated. Therefore, to increase the knowledge of intracellularcalcium and laser photon interaction, as well as to demonstrate differences in irradiation profiles with modern hand-pieces, we tested and compared the photobiomodulatory effect of 808â¯nm and 980â¯nm diode laser light by low- and higher-energy (60s, 100â¯mW/cm2, 100â¯mW/cm2, 500â¯mW/cm2, 1000â¯mW/cm2, 1500â¯mW/cm2, 2000â¯mW/cm2) irradiated with a "standard" (Gaussian fluence distribution) hand-piece or with a "flat-top" (uniform fluence) hand-piece. For this purpose, we used the eukaryote unicellular-model Dictyostelium discoideum. The 808â¯nm and 980â¯nm infrared laser light, at the energy tested directly affect the stored Ca2+ homeostasis, independent of the mitochondrial respiratory chain activities. From an organism perspective, the effect on Ca2+-dependent signal transduction as the regulator of spore germination in Dictyostelium, demonstrates how a cell can respond quickly to the correct laser photonic stimulus through a different cellular pathway than the known light-chromophore(mitochondria) interaction. Additionally, both hand-piece designs tested were able to photobiomodulate the D. discoideum cell; however, the hand-piece with a flat-top profile, through uniform fluence levels allows more effective and reproducible effects.
Asunto(s)
Calcio/metabolismo , Dictyostelium/metabolismo , Germinación/efectos de la radiación , Homeostasis/efectos de la radiación , Esporas/metabolismo , Rayos Infrarrojos , Láseres de Semiconductores , Terapia por Luz de Baja Intensidad , Mitocondrias/metabolismo , Temperatura , Factores de TiempoRESUMEN
BACKGROUND: Noise is an environmental factor that has been associated with metabolic and sleep disorders. Sleep is a vital function, since it underpins physiologic processes and cognitive recovery and development. However, the effects of chronic noise exposure on the developing organism are still subject to debate. OBJECTIVE: The objective of the present study was to assess the effects of subchronic, high-level noise exposure on sleep, apnea, and homeostasis in juvenile rats. METHODS: Twenty-four 3-wk-old male Wistar rats were exposed to noise [[Formula: see text], [Formula: see text]] for 5 wk and 2 d during the 12-h rest period. Data on sleep stages, food and water intake, apnea, and body and organ weight were recorded. RESULTS: Five weeks of high-level noise exposure were associated with hyperphagia ([Formula: see text]), body weight gain ([Formula: see text]), a heavier thymus ([Formula: see text]), and heavier adrenal glands ([Formula: see text]). A sleep analysis highlighted microstructural differences in the active period: in particular, the mean daily amount of rapid eye movement (REM) sleep as a proportion of total sleep time (TST) was higher. The mean daily amount of non-REM (NREM) sleep was lower in the exposed group, meaning that the intergroup difference in the TST was not significant. During a 1-h, noise-free plethysmographic recording during the rest period, the mean total amount of active wakefulness (AW) was lower in the exposed group (by 9.1 min), whereas the mean duration of an episode of REM sleep was higher (by 1.8 min), and the TST was higher (by 10.7 min). DISCUSSION: Subchronic exposure of juvenile rats to high-intensity noise during the rest period was associated with some small but significant sleep disturbances, greater food and water intakes, greater body weight gain, and greater thymus and adrenal gland weights. The main effects of noise exposure on sleep were also observed in the 1-h plethysmography session after 5 wk of exposure. https://doi.org/10.1289/EHP4045.
Asunto(s)
Apnea/fisiopatología , Homeostasis/efectos de la radiación , Ruido/efectos adversos , Sueño/efectos de la radiación , Animales , Apnea/etiología , Masculino , Ratas/crecimiento & desarrollo , Ratas WistarRESUMEN
Light is involved in many critical physiological or biochemical processes of human beings, such as visual sensing and the production of vitamin D. Recent studies have showed that the lights of different wavelengths have a profound influence in life activities. For example, blue light promotes alertness, whereas green light (GL) induces sleep in mice. On the other hand, metabolic homeostasis is regulated by a variety of factors, including dietary habits and light exposure. Our study aims to study whether certain wavelength of light would affect metabolic status of mice. Mice were divided into normal diet-fed group and high-fat diet (HFD)-fed group, and then exposed to various colors of the light. Physiological parameters, such as body weight, food intake and water drinking were regularly measured. Glucose tolerance test and pyruvate tolerance test were simultaneously performed. After mice were humanely sacrificed, liver histology and serologic analysis were performed for detecting lipid levels. We found that GL group showed obvious glucose intolerance and increased levels of serum and liver lipid contents compared to white light group. Meanwhile, the expression levels of lipid metabolism-related genes were almost down-regulated in liver. Furthermore, melatonin receptor-1b and thyroid hormone receptor-ß expression levels were significantly lowered in liver of GL-treated obese mice, suggesting that these hormone pathways may mediate the changes of lipid metabolism. Our data indicate that GL has a detrimental effect on the energy metabolism and aggravates HFD-induced obesity in mice. In addition to malnutrition, the colors of the lights also have a profound influence in the metabolic homeostasis and should be taken into consideration in the therapy of metabolic disorders.
Asunto(s)
Dieta Alta en Grasa , Metabolismo Energético/efectos de la radiación , Luz , Metabolismo de los Lípidos/efectos de la radiación , Enfermedades Metabólicas/metabolismo , Obesidad/metabolismo , Animales , Peso Corporal/efectos de la radiación , Ingestión de Alimentos/efectos de la radiación , Homeostasis/efectos de la radiación , Hígado/efectos de la radiación , Masculino , Enfermedades Metabólicas/sangre , Ratones , Ratones Endogámicos C57BL , Obesidad/sangreRESUMEN
The postmenopausal state is associated with an increased risk of metabolic disorder including reduced energy expenditure and weight gain, leading to higher cardiovascular and cancer risks among other diseases. Mitochondrial-derived peptide (MOTS-c) is a 16-amino acid peptide encoded by mitochondrial DNA. Here, we showed that MOTS-c treatment in mice prevented ovariectomy-induced obesity and insulin resistance. After ovariectomy, low levels of estrogens increased fat mass overload and disturbed normal adipose function, forcing the development of insulin resistance. MOTS-c treatment increased brown fat activation and reduced OVX-induced fat accumulation and inflammatory invasion in white adipose tissue, which contributes to the lower level of fatty acid in serum and liver. Moreover, MOTS-c activated AMPK pathway to improve energy dissipation and insulin sensitivity. And a blocker of AMPK pathway was found to attenuate the role of MOTS-c in the regulation of adipocyte lipid metabolism. In conclusion, MOTS-c is a high potential candidate for chronic treatment of menopausal induced metabolic dysfunction. KEY MESSAGES: ⢠MOTS-c prevents ovariectomy (OVX)-induced body weight gain and insulin resistance. ⢠MOTS-c reduces fat mass and suppresses inflammatory response under OVX condition. ⢠MOTS-c sustains the activity of the brown adipose under OVX condition. ⢠MOTS-c mediates AMPK pathway activation to control adipose metabolic homeostasis.
Asunto(s)
Tejido Adiposo/metabolismo , Homeostasis/fisiología , Resistencia a la Insulina , Enfermedades Metabólicas/metabolismo , Proteínas Mitocondriales/fisiología , Proteínas Quinasas Activadas por AMP/metabolismo , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Tejido Adiposo/efectos de los fármacos , Animales , Grasas/metabolismo , Femenino , Homeostasis/efectos de la radiación , Humanos , Inflamación/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismo , Enfermedades Metabólicas/etiología , Ratones , Ratones Endogámicos C57BL , Proteínas Mitocondriales/farmacología , Obesidad/etiología , Obesidad/metabolismo , Ovariectomía , Aumento de PesoRESUMEN
The solar radiation range has harmful and beneficial effects. Sunscreens, which selectively block specific spectral regions, may potentially interfere with skin homeostasis. For instance, the ultraviolet (UV) B waveband produces erythema and DNA damage; simultaneously, it induces pre-vitamin D3 synthesis. UVA1 and visible light can both induce pigmentation in skin phototypes IV-VI, and act in synergy to induce erythema and persistent pigment darkening. In contrast, UVA may contribute to blood pressure control and cardioprotection by inducing release of nitric oxide from intracutaneous photolabile nitric oxide derivatives. Finally, infrared A radiation alters the collagen equilibrium of the dermal extracellular matrix but is involved in the regulation of body temperature and in nitric oxide release, with a potential beneficial impact on blood pressure regulation. Ideally, photoprotection should thus be performed with a neutral density filter, mitigating all radiation ranges homogeneously, to maintain solar spectrum homeostasis. Natural compounds such as mycosporine-like amino acids are promising natural UV radiation-filtering compounds for an improved homeostasis with our environment. Lastly, we should not forget individual characteristics and behavior, as homeostasis differs according to individual phototypes and skin exposure behaviors.