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Radiation therapy for cancer treatment brings about a series of radiation injuries to normal tissues. In recent years, the discovery of copper-regulated cell death, cuproptosis, a novel form of programmed cell death, has attracted widespread attention and exploration in various biological functions and pathological mechanisms of copper metabolism and cuproptosis. Understanding its role in the process of radiation injury may open up new avenues and directions for exploration in radiation biology and radiation oncology, thereby improving tumor response and mitigating adverse reactions to radiotherapy. This review provides an overview of copper metabolism, the characteristics of cuproptosis, and their potential regulatory mechanisms in radiation injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal connections that could influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Increasing the seed germination potential and seedling growth rates play a pivotal role in increasing overall crop productivity. Seed germination and early vegetative (seedling) growth are critical developmental stages in plants. High-power microwave (HPM) technology has facilitated both the emergence of novel applications and improvements to existing in agriculture. The implications of pulsed HPM on agriculture remain unexplored. In this study, we have investigated the effects of pulsed HPM exposure on barley germination and seedling growth, elucidating the plausible underlying mechanisms. Barley seeds underwent direct HPM irradiation, with 60 pulses by 2.04 mJ/pulse, across three distinct irradiation settings: dry, submerged in deionized (DI) water, and submerged in DI water one day before exposure. Seed germination significantly increased in all HPM-treated groups, where the HPM-dry group exhibited a notable increase, with a 2.48-fold rise at day 2 and a 1.9-fold increment at day 3. Similarly, all HPM-treated groups displayed significant enhancements in water uptake, and seedling growth (weight and length), as well as elevated levels of chlorophyll, carotenoids, and total soluble protein content. The obtained results indicate that when comparing three irradiation setting, HPM-dry showed the most promising effects. Condition HPM seed treatment increases the level of reactive species within the barley seedlings, thereby modulating plant biochemistry, physiology, and different cellular signaling cascades via induced enzymatic activities. Notably, the markers associated with plant growth are upregulated and growth inhibitory markers are downregulated post-HPM exposure. Under optimal HPM-dry treatment, auxin (IAA) levels increased threefold, while ABA levels decreased by up to 65 %. These molecular findings illuminate the intricate regulatory mechanisms governing phenotypic changes in barley seedlings subjected to HPM treatment. The results of this study might play a key role to understand molecular mechanisms after pulsed-HPM irradiation of seeds, contributing significantly to address the global need of sustainable crop yield., 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 Inc. All rights reserved.)

Reactive oxygen species (ROS) hold great potential in tumor pyroptosis therapy, yet they are still limited by short species lifespan and limited diffusion distance. Inducing cells into a metastable state and then applying external energy can effectively trigger pyroptosis, but systemic sensitization still faces challenges, such as limited ROS content, rapid decay, and short treatment windows. Herein, a nanohybrid-based redox homeostasis-perturbator system was designed that synergistically induce early lysosomal escape, autophagy inhibition, and redox perturbation functions to effectively sensitize cells to address these challenges. Specifically, weakly alkaline layered double hydroxide nanosheets (LDH NSs) with pH-responsive degradation properties enabled early lysosomal escape within 4 h, releasing poly(L-dopa) nanoparticles for inducing catechol-quinone redox cycling in the cytoplasm. The intracellular ROS levels were systematically rebounded by 3-4 times in tumor cells and lasted for over 4 h. Subsequently induced lysosomal stress and Ca 2+ signaling activation resulted in severe mitochondrial dysfunction, as well as a perilous metastable state. Thereby, sequential near-infrared light was applied to trigger amplified stress through a local photothermal conversion. This led to sufficiently high levels of cleaved caspase-1 and GSDMD activation (2.5-2.8-fold increment) and subsequent pyroptosis response. In addition, OH - released by LDH elevated pH to alleviate the limitation of glutathione depletion by quinones at acidic pH and inhibit protective autophagy. Largely secreted inflammatory factors (2.5-5.6-fold increment), efficient maturation of dendritic cells, and further immune stimulation were boosted for tumor inhibition as a consequence. This study offers a new paradigm and insights into the synergy of internal systematic cellular sensitization and sequential external energy treatment to achieve tumor suppression through pyroptosis.

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 (Tert High ) cell population located in the ductal region of the adult SMG. These Tert High cells contribute to ductal cell generation during SMG homeostasis and to both ductal and acinar cell renewal 1 year after radiotherapy. Tert High 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 Tert High 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 Tert High 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., (© 2024 Guan et al.; Published by Cold Spring Harbor Laboratory Press.)

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/cm 2 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., 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 Elsevier B.V. All rights reserved.)

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 31 phosphorus-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.

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., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The main difficulty of radiotherapy is to destroy cancer cells without depletion of healthy tissue [...].

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Okuliarova, Mazgutova, Majzunova, Rumanova and Zeman.)

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 H 2 O 2 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 H 2 O 2 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.

The aim of the current study is to investigate the effect of daily long-term radio-frequency electromagnetic field (RF-EMFs) exposure on thiol/disulphide homeostasis and oxidant-antioxidant status in the serum of rats. Fourteen male Sprague Dawley rats were divided into two equal groups (n = 7). They were grouped as group 1 (sham-control) and group 2 (2100 MHz exposed). Group 2 rats were exposed to GSM-like signals for 5 h/day, 7 days per week for 14 days. In serum of blood samples, the native, total and native/total thiol levels and antioxidant-oxidant parameters were analyzed. The study revealed that the mean serum total thiol levels of GSM exposure group was rather higher than sham-control group ( p = 0,219); the mean serum native thiol levels of GSM exposure group was rather higher than sham-control group ( p = 0,416), and the mean serum disulphide levels of GSM exposure group was rather higher than sham-control group ( p = 0,566). On the other hand, the mean serum total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI) of GSM exposure group were higher than sham-control group. There are no data in the literature, that examine the effects of RF-EMFs on thiol/disulphide homeostasis. The results of this study, indicate that RF-EMFs did not cause oxidative stress and statistically changes in thiol/disulphide homeostasis. More sample sizes and longer-term exposures are needed to confirm the results of this study.

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.

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.

Calbindin‑D28K (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, Bcl‑2 and caspase‑12 were measured by western blot analysis. The intracellular Ca2+ concentration of control HLECs increased significantly following UVB irradiation, whereas in Calb1‑overexpressing cells, the Ca2+ levels remained steady. In the control cells, the expression of Bad and caspase‑12 was upregulated, and that of Bcl‑2 was downregulated. Notably, during UVB radiation‑induced apoptosis, the overexpression of Calb1 inhibited cell death, resulting in the decreased expression of Bad and caspase‑12, and in the upregulated expression of Bcl‑2. These results suggested that Calb1 inhibited the upregulation of genes involved in apoptosis. The siRNA‑mediated knockdown of Calb1 resulted in increased rates of UVB radiation‑induced apoptosis, the increased expression of Bad and caspase‑12, and the decreased expression of Bcl‑2, further demonstrating that Calb1 may mediate UVB radiation‑mediated 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 pro‑apoptotic genes in HLECs. Calb1 may thus inhibit the UVB radiation‑induced apoptosis of HLECs by regulating Ca2+.

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 CD45 lo /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.

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/cm 2 average power density, 0.2 J/cm 2 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., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (Copyright © 2020 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.)

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 intracellular‑calcium 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 808 nm and 980 nm diode laser light by low- and higher-energy (60s, 100 mW/cm 2 , 100 mW/cm 2 , 500 mW/cm 2 , 1000 mW/cm 2 , 1500 mW/cm 2 , 2000 mW/cm 2 ) 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 808 nm and 980 nm infrared laser light, at the energy tested directly affect the stored Ca 2+ homeostasis, independent of the mitochondrial respiratory chain activities. From an organism perspective, the effect on Ca 2+ -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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Group 3 innate lymphoid cells (ILC3s) are major regulators of inflammation, infection, microbiota composition and metabolism 1 . ILC3s and neuronal cells have been shown to interact at discrete mucosal locations to steer mucosal defence 2,3 . 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.

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-β 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., (Copyright © 2019 Elsevier Inc. All rights reserved.)

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.

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.

Radiotherapy is one of the most widely used methods to treat human tumors. Efficacy is due mainly to the DNA damage it induces. However, tumor cells often develop responsive adaptiveness to radiation treatment to survive, which leads to radioresistance. Many cellular processes, such as DNA damage repair, cell cycle arrest and autophagy, are involved in the development of radioresistance. Few interventions to combat radioresistance exist to date. In recent years, the lysosome has been reported to contribute to chemo- and radioresistance. Although for many years, the lysosome was known as an organelle that degrades waste materials, we now know it is also involved in important signaling pathways regulating cellular homeostasis. Although an increasing number of preclinical studies show that lysosome-related factors promote radioresistance, the role of the lysosome in radioresistance has not been systematically demonstrated. Here, we combine an updated understanding of lysosomes with a review of current studies regarding the role of lysosomes in mediating radioresistance., (Copyright © 2018. Published by Elsevier B.V.)

Radiotherapy represents a major anti-cancer modality and effectively kills cancer cells through generation of reactive oxygen species (ROS). However, cancer cells are commonly characterized by increased activity of ROS-scavenging enzymes in adaptation to intrinsic oxidative stress, leading to radioresistance. Abrogation of this defense network by pharmacological ROS insults therefore is shown to improve radioresponse in preclinical models; some of them are then tested in clinical trials. In this review, we address (1) the importance of ROS in radioresponse, (2) the main systems regulating redox homeostasis with a special focus on their prognostic effect and predictive role in radiotherapy, and (3) the potential radiosensitizers acting through inhibition of antioxidant enzymes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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 D 3 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.

Background: Childhood cancer survivors exposed to abdominal radiation (abdRT) are at increased risk for both insulin-dependent and non-insulin-dependent diabetes. We sought to clarify the pathophysiology of diabetes after abdRT by performing dynamic studies of insulin and glucose and testing for type 1 diabetes-associated autoantibodies., Procedure: Cross-sectional analysis of 2-year childhood cancer survivors treated with abdRT at age ≤21 years who underwent oral glucose tolerance testing and assessment of diabetes-related autoantibodies from December 2014 to September 2016. Prevalence of insulin/glucose derangements, indices of insulin sensitivity/secretion (homeostatic model assessment of insulin resistance [HOMA-IR], whole-body insulin sensitivity, insulinogenic index), autoantibody positivity, and treatment/demographic factors associated with adverse metabolic outcomes were assessed., Results: Among 40 participants previously exposed to abdRT (57.5% male; median age at cancer diagnosis, 3.3 years [range, 0.5-20.1]; median age at study 14.3 years [range, 8.3-49.8]; none with obesity), 9 (22.5%) had glucose derangements (n = 4 with impaired fasting glucose [≥100 mg/dL]; n = 4 with impaired glucose tolerance [2-hour glucose 140-199 mg/dL]; n = 1 with previously unrecognized diabetes [2-hour glucose ≥200 mg/dL]). Three of the four individuals with impaired fasting glucose also had insulin resistance, as measured by HOMA-IR; an additional four subjects with normal glucose tolerance were insulin resistant. The subject with diabetes had normal HOMA-IR. No participant had absolute insulinopenia or >1 positive diabetes-related autoantibody., Conclusions: This study suggests that radiation-induced damage to the insulin-producing β-cells is an unlikely explanation for the early derangements in glucose metabolism observed after abdRT. Research into alternative pathways leading to diabetes after abdRT is needed., (© 2018 Wiley Periodicals, Inc.)

In vivo, mammalian cells reside in an environment of 0.5-10% O 2 (depending on the tissue location within the body), whilst standard in vitro cell culture is carried out under room air. Little is known about the effects of this hyperoxic environment on treatment-induced oxidative stress, relative to a physiological oxygen environment. In the present study we investigated the effects of long-term culture under hyperoxia (air) on photodynamic treatment. Upon photodynamic irradiation, cells which had been cultured long-term under hyperoxia generated higher concentrations of mitochondrial reactive oxygen species, compared with cells in a physioxic (2% O 2 ) environment. However, there was no significant difference in viability between hyperoxic and physioxic cells. The expression of genes encoding key redox homeostasis proteins and the activity of key antioxidant enzymes was significantly higher after the long-term culture of hyperoxic cells compared with physioxic cells. The induction of antioxidant genes and increased antioxidant enzyme activity appear to contribute to the development of a phenotype that is resistant to oxidative stress-induced cellular damage and death when using standard cell culture conditions. The results from experiments using selective inhibitors suggested that the thioredoxin antioxidant system contributes to this phenotype. To avoid artefactual results, in vitro cellular responses should be studied in mammalian cells that have been cultured under physioxia. This investigation provides new insights into the effects of physioxic cell culture on a model of a clinically relevant photodynamic treatment and the associated cellular pathways., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Leptin has a central role in the maintenance of energy homeostasis, and its sensitivity is influenced by both the photoperiod and dietary polyphenols. The aim of this study was to investigate the effect of seasonal consumption of polyphenol-rich fruits on the hypothalamic leptin signaling system in non-obese and obese animals placed under different photoperiods. Non-obese and diet-induced obese male Fischer 344 rats were placed under either a short-day (SD) or long-day (LD) photoperiod and were supplemented with either 100 mg/kg of lyophilized red grapes or cherries. In non-obese animals, both fruits reduced energy balance independent of the photoperiod to which they were placed. However, the hypothalamic gene expression of Pomc was significantly up-regulated only in the SD photoperiod. In contrast, in obese animals only cherry significantly decreased the energy balance, although both fruits were able to counteract the diet-induced increase in hypothalamic AgRP mRNA levels when consumed during the SD photoperiod. In conclusion, the consumption of rich-polyphenol fruits may increase leptin sensitivity through the modulation of the hypothalamic leptin signal pathway mainly when consumed in the SD photoperiod. Therefore, fruit seasonality should be considered, as it can influence energy homeostasis and obesity.

Blue light (BL) suppression accelerates the senescence rate of wheat (Triticum aestivum L.) leaves exposed to shading. In order to study whether this effect involves the alteration of different cytokinin (CK) metabolites, CK-degradation, as well as the expression profile of genes responsible of CK-perception, -inactivation, -reactivation and/or -turnover, leaf segments of 30 day-old plants were placed in boxes containing bi-distilled water and covered with blue (B) or green (G) light filters, which supplied a similar irradiance but differed in the percentage of BL transmitted (G << B). A neutral (N) filter was used as control. When appropriate, different CK metabolites or an inhibitor of CK-degradation were added in order to alter the endogenous CK levels. A rapid decrement of trans-zeatin (tZ) and cis-zeatin (cZ) content was observed after leaf excision, which progressed at a higher rate in treatment G than in the control and B treatments. Senescence progression correlated with an accumulation of glycosylated forms (particularly cZ-derivatives), and an increment of CK-degradation, both of which were slowed in the presence of BL. On the contrary, CK-reactivation (analyzed through TaGLU1-3 expression) was delayed in the absence of BL. When different CK were exogenously supplied, tZ was the only natural free base capable to emulate the senescence-retarding effect of BL. Even though the signaling components involved in the regulation of senescence rate and CK-homeostasis by BL remain elusive, our data suggest that changes in the expression profile and/or functioning of the transcription factor HY5 might play an important role., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Diabetic peripheral neuropathy (DPN) is a nervous disorder caused by diabetes mellitus, affecting about 50% of patients in clinical medicine. Chronic pain is one of the major and most unpleasant symptoms developed by those patients, and conventional available treatments for the neuropathy, including the associated pain, are still unsatisfactory and benefit only a small number of patients. Photobiomodulation (PBM) has been gaining clinical acceptance once it is able to promote early nerve regeneration resulting in significant improvement in peripheral nerves disabilities. In this work, the effects of PBM (660 nm, 30 mW, 1.6 J/cm 2 , 0.28 cm 2 , 15 s in a continuous frequency) on treating DPN-induced pain and nerve damage were evaluated in an experimental model of diabetic-neuropathy induced by streptozotocin in mice. PBM-induced antinociception in neuropathic-pain mice was dependent on central opioids release. After 21 consecutive applications, PBM increased nerve growth factor levels and induced structural recovery increasing mitochondrial content and regulating Parkin in the sciatic nerve of DPN-mice. Taking together, these data provide new insights into the mechanisms involved in the effects of PBM-therapy emphasizing its therapeutic potential in the treatment of DPN., (© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Maintenance of tissue integrity during development and homeostasis requires the precise coordination of several cell-based processes, including cell death. In animals, the majority of such cell death occurs by apoptosis, a process mediated by caspase proteases. To elucidate the role of caspases in tissue integrity, we investigated the behavior of Drosophila epithelial cells that are severely compromised for caspase activity. We show that these cells acquire migratory and invasive capacities, either within 1-2 days following irradiation or spontaneously during development. Importantly, low levels of effector caspase activity, which are far below the threshold required to induce apoptosis, can potently inhibit this process, as well as a distinct, developmental paradigm of primordial germ cell migration. These findings may have implications for radiation therapy in cancer treatment. Furthermore, given the presence of caspases throughout metazoa, our results could imply that preventing unwanted cell migration constitutes an ancient non-apoptotic function of these proteases.

Background: Osteoradionecrosis of the jaw (ORNJ) is the most severe and complex sequel of head and neck radiotherapy (RT) because of the bone involved, it may cause pain, paresthesia, foul odor, fistulae with suppuration, need for extra oral communication and pathological fracture. We treated twenty lesions of ORNJ using low-level laser therapy (LLLT) and antimicrobial photodynamic therapy (aPDT). The objective of this study was to stimulate the affected area to homeostasis and to promote the healing of the oral mucosa., Methods: We performed aPDT on the exposed bone, while LLLT was performed around the bone exposure (red spectrum) and on the affected jaw (infrared spectrum). Monitoring and clinical intervention occurred weekly or biweekly for 2 years., Results: 100% of the sample presented clinical improvement, and 80% presented complete covering of the bone exposure by intact oral mucosa., Conclusion: LLLT and aPDT showed positive results as an adjuvant therapy to treat ORNJ.

Vision in dim light depends on synapses between rods and rod bipolar cells (RBCs). Here, we find that these synapses exist in multiple configurations, in which single release sites of rods are apposed by one to three postsynaptic densities (PSDs). Single RBCs often form multiple PSDs with one rod; and neighboring RBCs share ~13% of their inputs. Rod-RBC synapses develop while ~7% of RBCs undergo programmed cell death (PCD). Although PCD is common throughout the nervous system, its influences on circuit development and function are not well understood. We generate mice in which ~53 and ~93% of RBCs, respectively, are removed during development. In these mice, dendrites of the remaining RBCs expand in graded fashion independent of light-evoked input. As RBC dendrites expand, they form fewer multi-PSD contacts with rods. Electrophysiological recordings indicate that this homeostatic co-regulation of neurite and synapse development preserves retinal function in dim light.

The aim of this study was to investigate how controlled UVB irradiation in combination with reduced nutritional vitamin D (vitD) supply affects vitD status and Ca metabolism of growing goats and sheep. The hypothesis was that, like dairy cows, goats and sheep are able to compensate for the missing nutritional supply of vitD through endogenous production in the skin, with the consequence of a high vitD status and a balanced Ca homeostasis. Sixteen lambs and 14 goat kids aged 3 and a half months were housed in an UVB free environment and fed hay and a vitD-free concentrate over a period of 13 wk. One group of each species was exposed to UVB lamps daily during individual feeding; the other groups served as controls. Serum, urine, and feces samples were taken at the start and at a monthly interval. Serum was analyzed for vitD metabolites, bone markers, growth hormone, insulin-like growth factor I, Ca, and P. Apparent digestibility and urinary excretion of Ca and P were determined. The left metatarsus was analyzed by peripheral quantitative computer tomography for bone mineral density before starting and at the end of the trial. In wk 13, all animals were slaughtered and samples of skin, rumen, duodenum, kidney, and bone (metatarsus) were collected. Content of sterols of vitD synthesis in the skin, Ca flux rates in rumen and duodenum, expression of vitD receptor in duodenum and kidney, renal and intestinal gene expression of Ca transport proteins, and renal enzymes related to vitD metabolism were determined. The UVB exposure led to lower 7-dehydrocholesterol content in the skin and a better vitD status (higher serum 25-hydroxyvitamin D), but no signs of vitD deficiency were seen in the control groups and no effect of irradiation was detected in the analyzed parameters of Ca homeostasis. Differences between the 2 species were detected: lambs had a higher increase of bone mineral density, lower values of bone markers, growth hormone, and insulin-like growth factor I in serum and higher tachysterol and lower lumisterol content in skin compared with goat kids. The results indicated that growing lambs and goat kids are able to compensate for a vitD-reduced diet by cutaneous vitD synthesis when exposed to UVB irradiation and therefore to keep a high vitD status. In contrast, when a reduced vitD diet is combined with missing UVB exposure, the vitD status drops, but the experimental time was probably too short to induce a vitD deficiency or an effect on Ca homeostasis., (Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Despite the significant impacts of light on nitric oxide (NO) levels in plants, the mechanism underlying the influence of this environmental factor on NO metabolism remains poorly understood. A critical mechanism controlling NO levels in plant cells relies on the S-nitrosylation of glutathione (GSH), giving rise to S-nitrosoglutathione (GSNO), which can be either stored or degraded depending on the cellular context. Here, we demonstrate that a strict balance is maintained between NO generation and scavenging during tomato (Solanum lycopersicum) seedling deetiolation. Given the absence of accurate methods in the literature to estimate NO scavenging in planta, we first developed a simple, robust system to continuously monitor the global in vivo NO scavenging by plant tissues. Then, using photomorphogenic tomato mutants, we demonstrated that the light-evoked de-etiolation is associated with a dramatic rise in NO content followed by a progressive increment in NO scavenging capacity of the tissues. Light-driven increments in NO scavenging rates coincided with pronounced rises in S-nitrosothiol content and GSNO reductase (GSNOR) activity, thereby suggesting that GSNO formation and subsequent removal via GSNOR might be key for controlling NO levels during seedling deetiolation. Accordingly, treatments with thiol-blocking compounds further indicated that thiol nitrosylation might be critically involved in the NO scavenging mechanism responsible for maintaining NO homeostasis during deetiolation. The impacts of both light and NO on the transcriptional profile of glutathione metabolic genes also revealed an independent but coordinated action of these signals on the regulation of key components of glutathione and GSNO metabolisms. Altogether, these data indicated that GSNO formation and subsequent removal might facilitate maintaining NO homeostasis during light-driven seedling deetiolation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

In recent years, there has been a dramatic increase in the number and variety of electronic devices that emit electromagnetic waves. Because people live and work in close proximity to these pieces of electrical equipment, there is growing concern surrounding the destruction of homeostasis by electromagnetic field exposure. In the present study, the effects of 60 Hz 0.8 mT extremely low-frequency electromagnetic fields (ELF-EMF) on a macrophage cell line (RAW 264.7) were examined. Under defined ELF-EMF exposure conditions, the production of nitric oxide and pro-inflammatory cytokines, TNF-α, IL-1β, and IL-6, were increased in RAW 264.7 cells and the expression of those genes was also upregulated. However, cell proliferation was not altered. Translocation of NF-κB (nuclear factor kappa B), molecules that act downstream of the pro-inflammatory cytokines, were increased to the nucleus under ELF-EMF exposure conditions. In addition, we found that ELF-EMF exposure elevated activation of nuclear factor of activated T cells (NFAT) 2, as well as positively affected the influx of calcium. Furthermore, with both the presence of a potent antioxidant (Resveratrol) and downregulation of the antioxidant-related gene Prx-1 (Peroxiredoxin-1), ELF-EMF was associated with higher inflammatory responses of macrophages. These results suggest that an ELF-EMF amplifies inflammatory responses through enhanced macrophage activation and can decrease the effectiveness of antioxidants. Bioelectromagnetics. 38:374-385, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Extremely low-frequency electromagnetic field (ELFEMF) can stimulate neural differentiation in human bone marrow-derived mesenchymal cells (hBM-MSCs), and this provides an opportunity for research on neurodegenerative diseases such as Alzheimer's disease (AD). Metallothionein-3 (MT3), an isoform of the metal-binding proteins, metallothioneins, involved in maintaining intracellular zinc (Zn) homeostasis and the deregulation of zinc homeostasis, has separately been implicated in AD. Here, we investigated the effect of ELFEMF-induced neural differentiation of hBM-MSCs on Zn-MT3 homeostatic interaction. Exposure to ELFEMF induced neural differentiation of hBM-MSCs, which was characterized by decreased proliferation and enhanced neural-like morphology. We observed expression of neuronal markers such as β-tubulin3, pleiotrophin, and neurofilament-M at the mRNA level and MAP2 at the protein level. ELFEMF-induced neural differentiation correlated with decreased expression of metal-response element-transcription factor 1 and MT3, as well as decreased intracellular Zn concentration. In addition, upregulation of dihydropyrimidinase-related protein 2 was observed, but there was no change in γ-enolase expression. These data indicate a possible regulatory mechanism for MT3 during neural differentiation. Our findings provide considerable insight into molecular mechanisms involved in neural differentiation, which is useful for developing new treatments for neurodegenerative diseases. Bioelectromagnetics. 38:364-373, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

One of the hallmarks of cancer consists in the ability of tumor cells to divide indefinitely, and to maintain stable telomere lengths throughout the activation of specific telomere maintenance mechanisms (TMM). Therefore in the last fifteen years, researchers proposed to target telomerase or telomeric structure in order to block limitless replicative potential of cancer cells providing a fascinating strategy for a broad-spectrum cancer therapy. In the present review, we report in vitro and in vivo evidence regarding the use of chemical agents targeting both telomerase or telomere structure and showing promising antitumor effects when used in combination with ionizing radiation (IR). RNA interference, antisense oligonucleotides (e.g., GRN163L), non-nucleoside inhibitors (e.g., BIBR1532) and nucleoside analogs (e.g., AZT) represent some of the most potent strategies to inhibit telomerase activity used in combination with IR. Furthermore, radiosensitizing effects were demonstrated also for agents acting directly on the telomeric structure such as G4-ligands (e.g., RHPS4 and Telomestatin) or telomeric-oligos (T-oligos). To date, some of these compounds are under clinical evaluation (e.g., GRN163L and KML001). Advantages of Telomere/Telomerase Targeting Compounds (T/TTCs) coupled with radiotherapy may be relevant in the treatment of radioresistant tumors and in the development of new optimized treatment plans with reduced dose adsorbed by patients and consequent attenuation of short- end long-term side effects. Pros and cons of possible future applications in cancer therapy based on the combination of T/TCCs and radiation treatment are discussed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To evaluate thiol-disulphide homeostasis - a novel, easily calculated, readily available, and relatively cheap oxidative stress marker - in radiation workers and compare the results with healthy controls., Materials and Methods: A total of 108 participants were enrolled in the study including 63 hospital workers occupationally exposed to ionizing radiation in the units of interventional radiology, interventional cardiology and nuclear medicine. A control group consisted of 45 individuals staff in the same hospital. Serum thiol-disulphide homeostasis measurement was investigated via the spectrophotometric method newly described by Erel and Neşelioğlu., Results: The mean serum native thiol levels of radiation workers (528.96 ± 86.42 μmol/l) was significantly lower than control subjects (561.05 ± 104.83 μmol/l) (p = .045). The mean serum total thiol levels of radiation workers (547.70 ± 91.50 μmol/l) was lower than control subjects (580.36 ± 112.24 μmol/l). Nevertheless, there was no significant difference between total thiol of exposed workers and controls., Conclusions: The results show that long-term low dose ionizing radiation may lead to oxidative stress and have side-effects in antioxidant thiol groups. We may suggest supporting radiation workers by safe antioxidant nutritional formulations and following up via both physical dosimetry and biodosimetric methods.

The aim of this study was to prove whether pigs are able to synthesize vitamin D (vitD) in the skin and to investigate the influence of ultraviolet irradiation (UVB) on vitD status and calcium (Ca) homeostasis of growing pigs. Thirty-two 11-week-old pigs were kept without access to sunlight and divided into four groups receiving the following treatment in a 2 × 2 factorial design: (i) UVB irradiation or not and (ii) vitD in feed or not. Blood, urine and faeces were sampled every third week. In serum, vitD metabolites, Ca, phosphorus (P), magnesium (Mg) and bone markers were analysed. Digestibility of Ca, P and Mg as well as urinary excretion of these minerals was analysed. After 14 weeks, the animals were slaughtered, and samples of skin, intestines, kidneys and bones (metatarsus) were taken for further analyses: sterols of vitD synthesis in the skin, Ca flux rates in the intestines, expression of genes involved in Ca transport in the intestines and kidneys, bone mineral density (BMD) with the aid of peripheral quantitative computer tomography and bone mineral content by ashing the metatarsus. Irradiated animals showed higher levels of 7-dehydrocholesterol and tachysterol in the skin, higher levels of 25-hydroxycholecalciferol and 1,25-dihydroxycholecalciferol in the serum and higher Ca net flux rates were determined in Ussing chambers. In contrast, the expression of genes involved in Ca transport in the intestines and kidneys was not altered. Similarly, the digestibility of Ca and P as well as the urinary excretion was not affected. With respect to the metatarsus, no differences in mineral contents and BMD were found between groups. At the end of the study, some subclinical signs of beginning vitD 'insufficiency' were observed in the group without access to vitD (represented by higher expression of 1α-hydroxylase in the kidney and increased parathyroid hormone in serum)., (Journal of Animal Physiology and Animal Nutrition © 2017 Blackwell Verlag GmbH.)

Sleep-or sleep-like states-have been reported in adult and larval zebrafish using behavioural criteria. These reversible quiescent periods, displaying circadian rhythmicity, have been used in pharmacological, genetic and neuroanatomical studies of sleep-wake regulation. However, one of the important criteria for sleep, namely sleep homeostasis, has not been demonstrated unequivocally. To study rest homeostasis in zebrafish larvae, we rest-deprived 1-week-old larvae with a novel, ecologically relevant method: flow of water. Stereotyped startle responses to sensory stimuli were recorded after the rest deprivation to study arousal threshold using a high-speed camera, providing an appropriate time resolution to detect species-specific behavioural responses occurring in a millisecond time-scale. Rest-deprived larvae exhibited fewer startle responses than control larvae during the remaining dark phase and the beginning of the light phase, which can be interpreted as a sign of rest homeostasis-often used as equivalent of sleep homeostasis. To address sleep homeostasis further, we probed the adenosinergic system, which in mammals regulates sleep homeostasis. The adenosine A1 receptor agonist, cyclohexyladenosine, administered during the light period, decreased startle responses and increased immobility bouts, while the adenosine antagonist, caffeine, administered during the dark period, decreased immobility bouts. These results suggest that the regulation of sleep homeostasis in zebrafish larvae consists of the same elements as that of other species., (© 2017 European Sleep Research Society.)

The thermophilic alga C. merolae thrives in extreme environments (low pH and temperature between 40°C and 56°C). In this study, we investigated the acclimation process of the alga to a colder temperature (25°C). A long-term cell growth experiment revealed an extensive remodeling of the photosynthetic apparatus in the first 250 h of acclimation, which was followed by cell growth to an even higher density than the control (grown at 42°C) cell density. Once the cells were shifted to the lower temperature, the proteins of the light-harvesting antenna were greatly down-regulated and the phycobilisome composition was altered. The amount of PSI and PSII subunits was also decreased, but the chlorophyll to photosystems ratio remained unchanged. The 25°C cells possessed a less efficient photon-to-oxygen conversion rate and require a 2.5 times higher light intensity to reach maximum photosynthetic efficiency. With respect to chlorophyll, however, the photosynthetic oxygen evolution rate of the 25°C culture was 2 times higher than the control. Quantitative proteomics revealed that acclimation requires, besides remodeling of the photosynthetic apparatus, also adjustment of the machinery for protein folding, degradation, and homeostasis. In summary, these remodeling processes tuned photosynthesis according to the demands placed on the system and revealed the capability of C. merolae to grow under a broad range of temperatures., (© 2017 American Society of Plant Biologists. All Rights Reserved.)

Homoeostatic regulation of the light sensor, rhodopsin, is critical for the maintenance of light sensitivity and survival of photoreceptors. The major fly rhodopsin, Rh1, undergoes light-induced endocytosis and degradation, but its protein and mRNA levels remain constant during light/dark cycles. It is not clear how translation of Rh1 is regulated. Here, we show that adult photoreceptors maintain a constant, abundant quantity of ninaE mRNA, which encodes Rh1. We demonstrate that the Fmr1 protein associates with ninaE mRNA and represses its translation. Further, light exposure triggers a calcium-dependent dephosphorylation of Fmr1, which relieves suppression of Rh1 translation. We demonstrate that Mts, the catalytic subunit of protein phosphatase 2A (PP2A), mediates light-induced Fmr1 dephosphorylation in a regulatory B subunit of PP2A (CKa)-dependent manner. Finally, we show that blocking light-induced Rh1 translation results in reduced light sensitivity. Our results reveal the molecular mechanism of Rh1 homoeostasis and physiological consequence of Rh1 dysregulation., (© The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.)

The effects of a static magnetic field (SMF) and the dihydrochalcones phloretin and phloridzin on the redox homeostasis of fibroblasts were investigated. The aim of the present study was to determine the redox homeostasis of fibroblasts that were simultaneously exposed to a static magnetic field and the dihydrochalcones phloretin and phloridzin. The fibroblasts were cultured for 72 h in special magnetic test chambers at different moderate intensities (0.4, 0.55 and 0.7 T). In this report, the activities of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), glutathione transferase (GST); the concentrations of malondialdehyde (MDA), adenosine triphosphate (ATP) and total antioxidant status were measured using commercially available kits. We did not observe any impairment in the redox balance in cells in fibroblasts that were only exposed to static magnetic fields of different intensities or In fibroblast cultured with dihydrochalcones and exposed to static magnetic field increase the SOD, GPx, GST activities and MDA concentration. Our investigations revealed that the activities of SOD, GPx, GST and the concentration of MDA that were determined for the fibroblasts that were cultured with dihydrochalcones were higher in the presence of a static magnetic field. Our results indicated that exposure to SMF (0.7 T) with dihydrochalcones induces oxidative stress in fibroblasts.

The conditioning regimen used as part of the Berlin patient's hematopoietic cell transplant likely contributed to his eradication of HIV infection. We studied the impact of conditioning in simian-human immunodeficiency virus-infected (SHIV-infected) macaques suppressed by combination antiretroviral therapy (cART). The conditioning regimen resulted in a dramatic, but incomplete depletion of CD4 + and CD8 + T cells and CD20 + B cells, increased T cell activation and exhaustion, and a significant loss of SHIV-specific Abs. The disrupted T cell homeostasis and markers of microbial translocation positively correlated with an increased viral rebound after cART interruption. Quantitative viral outgrowth and Tat/rev-induced limiting dilution assays showed that the size of the latent SHIV reservoir did not correlate with viral rebound. These findings identify perturbations of the immune system as a mechanism for the failure of autologous transplantation to eradicate HIV. Thus, transplantation strategies may be improved by incorporating immune modulators to prevent disrupted homeostasis, and gene therapy to protect transplanted cells., Competing Interests: Conflict of interest: The authors have declared that no conflict of interest exists.

The appearance of endogenous electromagnetic fields in biological systems is a widely debated issue in modern science. The electrophysiological fields have very tiny intensities and it can be inferred that they are rapidly decreasing with the distance from the generating structure, vanishing at very short distances. This makes very hard their detection using standard experimental methods. However, the existence of fast-moving charged particles in the macromolecules inside both intracellular and extracellular fluids may envisage the generation of localized electric currents as well as the presence of closed loops, which implies the existence of magnetic fields. Moreover, the whole set of oscillatory frequencies of various substances, enzymes, cell membranes, nucleic acids, bioelectrical phenomena generated by the electrical rhythm of coherent groups of cells, cell-to-cell communication among population of host bacteria, forms the increasingly complex hierarchies of electromagnetic signals of different frequencies which cover the living being and represent a fundamental information network controlling the cell metabolism. From this approach emerges the concept of electromagnetic homeostasis: that is, the capability of the human body to maintain the balance of highly complex electromagnetic interactions within, in spite of the external electromagnetic noisy environment. This concept may have an important impact on the actual definitions of heal and disease.

CO 2 laser has a beneficial effect on stem cells by mechanisms that are not clearly elucidated. We hypothesize that the effect of fractional CO 2 laser on human adipose-derived stem cells (ADSC) could be due to changes in redox homeostasis and secretion of factors contributing to cellular proliferation and angiogenic potential. ADSC incubated in medium containing 0.5 or 10 % FBS were exposed to a single irradiation of a 10,600-nm fractional CO 2 laser; non-irradiated ADSC were used as control. Viability/proliferation of ADSC was assessed by MTT assay; the intracellular reactive oxygen species (ROS) levels and the mitochondrial membrane potential (∆Ψ m ) were determined with DCFH-DA and JC-1 fluorescent probes, respectively. Molecules secreted by ADSC in the medium were determined by ELISA assay, and their capacity to support endothelial tube-like formation by the Matrigel assay. The results showed that compared to controls, ADSC kept in low FBS medium and irradiated with CO 2 laser at 9 W exhibited: (a) increased proliferation (∼20 %), (b) transient increase of mitochondrial ROS and the capacity to restore Δψ m after rotenone induced depolarization, and (c) augmented secretion in the conditioned medium of MMP-2 (twofold), MMP-9 (eightfold), VEGF (twofold), and adiponectin (∼50 %) that have the capacity to support angiogenesis of endothelial progenitor cells. In conclusion, the mechanisms underlying the benefic effect of CO 2 laser on ADSC are the activation of the redox pathways which increases cell proliferation and enhances secretion of angiogenic molecules. These results explain, in part, the mechanisms involved in the increased regenerative potential of CO 2 laser-exposed ADSC that could be exploited for clinical applications.

Regeneration of the intestinal epithelium is driven by multiple intestinal stem cell (ISC) types, including an active, radiosensitive Wnt high ISC that fuels turnover during homeostasis and a reserve, radioresistant Wnt low/off ISC capable of generating active Wnt high ISCs. We examined the role of the Msi family of oncoproteins in the ISC compartment. We demonstrated that Msi proteins are dispensable for normal homeostasis and self-renewal of the active ISC, despite their being highly expressed in these cells. In contrast, Msi proteins are required specifically for activation of reserve ISCs, where Msi activity is both necessary and sufficient to drive exit from quiescence and entry into the cell cycle. Ablation of Msi activity in reserve ISCs rendered the epithelium unable to regenerate in response to injury that ablates the active stem cell compartment. These findings delineate a molecular mechanism governing reserve ISC quiescence and demonstrate a necessity for the activity of this rare stem cell population in intestinal regeneration., (© 2016 Yousefi et al.)

Directional chloroplast photorelocation is a major physio-biochemical mechanism that allows these organelles to realign themselves intracellularly in response to the intensity of the incident light as an adaptive response. Signaling processes involved in blue light (BL)-dependent chloroplast movements were investigated in Hydrilla verticillata (L.f.) Royle leaves. Treatments with antagonists of actin filaments [2,3,5-triiodobenzoic acid (TIBA)] and microtubules (oryzalin) revealed that actin filaments, but not microtubules, play a pivotal role in chloroplast movement. Involvement of reactive oxygen species (ROS) in controlling chloroplast avoidance movement has been demonstrated, as exogenous H 2 O 2 not only accelerated chloroplast avoidance but also could induce chloroplast avoidance even in weak blue light (WBL). Further support came from experiments with different ROS scavengers, i.e., dimethylthiourea (DMTU), KI, and CuCl 2 , which inhibited chloroplast avoidance, and from ROS localization using specific stains. Such avoidance was also partially inhibited by ZnCl 2 , an inhibitor of NADPH oxidase (NOX) as well as 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU), a photosynthetic electron transport chain (ETC) inhibitor at PS II. However, methyl viologen (MV), a PS I ETC inhibitor, rather accelerated avoidance response. Exogenous calcium (Ca +2 ) induced avoidance even in WBL while inhibited chloroplast accumulation partially. On the other hand, chloroplast movements (both accumulation and avoidance) were blocked by Ca +2 antagonists, La 3+ (inhibitor of plasma membrane Ca +2 channel) and ethylene glycol-bis(2-aminoethylether)-N,N,N',N'-tetraacetic acid (EGTA, Ca +2 chelator) while LiCl that affects Ca +2 release from endosomal compartments did not show any effect. A model on integrated role of ROS and Ca +2 (influx from apolastic space) in actin-mediated chloroplast avoidance has been proposed.

The arrangement of β cells within islets of Langerhans is critical for insulin release through the generation of rhythmic activity. A privileged role for individual β cells in orchestrating these responses has long been suspected, but not directly demonstrated. We show here that the β cell population in situ is operationally heterogeneous. Mapping of islet functional architecture revealed the presence of hub cells with pacemaker properties, which remain stable over recording periods of 2 to 3 hr. Using a dual optogenetic/photopharmacological strategy, silencing of hubs abolished coordinated islet responses to glucose, whereas specific stimulation restored communication patterns. Hubs were metabolically adapted and targeted by both pro-inflammatory and glucolipotoxic insults to induce widespread β cell dysfunction. Thus, the islet is wired by hubs, whose failure may contribute to type 2 diabetes mellitus., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)