Collaborative Study of Thresholds for Mutagens: Adaptive Responses in the Micronucleus Test and Gene Induction by Mutagenic Treatments.

Background: We have been conducting a collaborative study on the thresholds of mutagens. In our previous examinations of cell activity and cell proliferation as endpoints, both displayed hormesis. This time, we conducted experiments to determine thresholds using the micronucleus test as an endpoint. Methods: The micronucleus test was conducted using Chinese hamster CHL/IU cells and mouse lymphoid L5178Y cells. Additionally, we conducted preliminary investigations into the gene expression using human TK6 cells. Results: When adhesive CHL/IU cells were treated with mitomycin C (MMC), and the hormetic response was examined, hormesis was not observed clearly. When L5178Y cells were treated with methyl methanesulfonate (EMS), AF-2, MMC, and colchicine, all of them exhibited an adaptive response. Additionally, cross-adaptive responses using AF-2 and MMC or EMS and MMC were conducted, both combinations showed a cross-adaptive response. When the gene expression patterns of six genes were investigated by RT-PCR after treatment with MMC, EMS, and H2O2 using TK6 cells, two genes, GADD45 A and P21, were induced in a dose- and time-dependent manner. Conclusion: Adaptive responses arise from preconditioning. As hormesis is inherently linked to preconditioning, adaptive responses observed in this study strongly suggest that hormesis was induced, hence existence of thresholds.

Emotional Stress Induces Adaptive Response in Rat Lymphocytes to Subsequent Ionizing Radiation Exposure.

We studied the molecular mechanisms of cross-adaptation to ionizing radiation (1 Gy) of lymphocytes isolated from rats subjected to emotional stress. The effects of chronic (CES; various types of stress exposure) and acute (AES; forced swimming) emotional stress in rats on indicators of oxidative stress, cell death, and levels of NRF2 and NOX4 proteins involved in the development of the adaptive response were analyzed in isolated lymphocytes. It was found that stress induced an adaptive response in rat lymphocytes and triggered processes similar to the adaptive response induced by low doses of ionizing radiation: an increase in the level of oxidized DNA and cell death, as well as an increase in the content of NOX4 and NRF2 proteins. In animals subjected to emotional stress, suppressed DNA oxidation in response to irradiation, reduced levels of protective factor NRF2, as well as lymphocyte death were observed.

Alzheimer's disease and low-dose radiation therapy: A new hope.

The concept of low-dose radiation (LDR)-induced hormetic responses was initially observed approximately 70 years ago and systematically reviewed along with the discovery of LDR-induced adaptive responses in a cytogenetic in vitro study in 1980s. By the end of the 1990s, discussions regarding the potential applications of LDR-induced hormesis and adaptive responses for preventing or treating chronic diseases, such as Alzheimer's disease (AD) had taken place. Until 2016, reports on radiotherapy for the subjects with AD and for genetic AD model mice were published. Subsequently, several preclinical studies with animal models of AD and clinical studies in AD subjects were conducted. A significant milestone was achieved with the online availability of a new Systematic Review based on qualified publications from these preclinical and clinical studies. This mini-review provides a concise historical introduction to LDR-induced hormesis and adaptive responses with discussion of AD radiotherapy with either LDR or relatively high dose radiation. Highlights of this Systematic Review cover promising outcomes, challenges, and new questions, followed by discussion of potential mechanisms.

Taurine induces hormesis in multiple biological models: May have transformative implications for overall societal health.

This paper represents the first integrative assessment and documentation of taurine-induced hormetic effects in the biological and biomedical areas, their dose response features, mechanistic frameworks, and possible public health, therapeutic and commercial applications. Taurine-induced hormetic effects are documented in a wide range of experimental models, cell types and for numerous biological endpoints, with most of these experimental findings being reported within the past five years. It is suggested that the concept of hormesis may have a transformative effect on taurine research and its public health and therapeutic applications.

RUTIN, a widely consumed flavonoid, that commonly induces hormetic effects.

Rutin is a flavonoid present in numerous fruits and vegetables and therefore widely consumed by humans. It is also a popular dietary supplement of 250-500 mg/day. There is considerable consumer interest in rutin due to numerous reports in the biomedical literature of its multi-system chemo-preventive properties. The present paper provides the first assessment of rutin-induced hormetic concentration/dose responses, their quantitative features and mechanistic basis, along with their biological, biomedical, clinical, and public health implications. The findings indicate that rutin-induced hormetic dose responses are widespread, being reported in numerous biological models and cell types for a wide range of endpoints. Of critical importance is that the optimal hormetic findings shown in in vitro systems are currently not achievable for human populations due to low gastrointestinal tract bioavailability. These findings have the potential to strengthen future experimental studies with rutin, particularly concerning study design parameters.

Adaptive metabolic response to short-term intensive fasting.

BACKGROUND & AIMS: Short-term intensive fasting (STIF), known as beego in Chinese phonetic articulation, has been practiced for more than two thousand years. However, the potential risk of STIF and the body's response to the risk have not been adequately evaluated. This study aims to address this issue, focusing on the STIF-triggered metabolic response of the liver and kidney. METHODS: The STIF procedure in the clinical trial includes a 7-day water-only intensive fasting phase and a 7-day gradual refeeding phase followed by a regular diet. The intensive fasting in humans was assisted with psychological induction. To gain insights not available in the clinical trial, we designed a STIF program for mice that resulted in similar phenotypes seen in humans. Plasma metabolic profiling and examination of gene expression as well as liver and kidney function were performed by omics, molecular, biochemical and flow cytometric analyses. A human cell line model was also used for mechanistic study. RESULTS: Clinically significant metabolites of fat and protein were found to accumulate during the fasting phase, but they were relieved after gradual refeeding. Metabolomics profiling revealed a universal pattern in the consumption of metabolic intermediates, in which pyruvate and succinate are the two key metabolites during STIF. In the STIF mouse model, the accumulation of metabolites was mostly counteracted by the upregulation of catabolic enzymes in the liver, which was validated in a human cell model. Kidney filtration function was partially affected by STIF but could be recovered by refeeding. STIF also reduced oxidative and inflammatory levels in the liver and kidney. Moreover, STIF improved lipid metabolism in mice with fatty liver without causing accumulation of metabolites after STIF. CONCLUSIONS: The accumulation of metabolites induced by STIF can be relieved by spontaneous upregulation of catabolic enzymes, suggesting an adaptive and protective metabolic response to STIF stress in the mammalian body.

Dietary conjugated linoleic acid downregulates the AlCl3-induced hyperactivation of compensatory and maladaptive signalling in the mouse brain cortex.

Oxidative stress, hyperactivation of compensatory mechanisms (unfolded protein response, UPR; nuclear factor erythroid 2-related factor 2, Nrf2) and the stimulation of maladaptive response (inflammation/apoptosis) are interconnected pathogenic processes occurring during Alzheimer's disease (AD) progression. The neuroprotective ability of dietary Conjugated linoleic acid (CLAmix) in a mouse model of AlCl3-induced AD was recently described but, the effects of AlCl3 or CLAmix intake on these pathogenic processes are still unknown. The effects of dietary AlCl3 or CLAmix - alone and in combination - were examined in the brain cortex of twenty-eight BalbC mice divided into 4 groups (n = 7 each). The neurotoxic effects of AlCl3 were investigated in animals treated for 5 weeks with 100 mg/kg/day (AL). CLAmix supplementation (600 mg/kg bw/day) for 7 weeks (CLA) was aimed at evaluating its modulatory effects on the Nrf2 pathway while its co-treatment with AlCl3 during the last 5 weeks of CLAmix intake (CLA + AL) was used to investigate its neuroprotective ability. Untreated mice were used as controls. In the CLA group, the NADPH oxidase (NOX) activation in the brain cortex was accompanied by the modulation of the Nrf2 pathway. By contrast, in the AL mice, the significant upregulation of oxidative stress markers, compensatory pathways (UPR/Nrf2), proinflammatory cytokines (IL-6, TNFα) and the proapoptotic protein Bax levels were found as compared with control. Notably, in CLA + AL mice, the marked decrease of oxidative stress, UPR/Nrf2 markers and proinflammatory cytokines levels were associated with the significant increase of the antiapoptotic protein Bcl2. The involvement of NOX in the adaptive response elicited by CLAmix along with its protective effects against the onset of several pathogenic processes triggered by AlCl3, broadens the knowledge of the mechanism underlying the pleiotropic activity of Nrf2 activators and sheds new light on their potential therapeutic use against neurodegenerative disorders.

Interplay of immune modulation, adaptive response and hormesis: Suggestive of threshold for clinical manifestation of effects of ionizing radiation at low doses?

The health impacts of low-dose ionizing radiation exposures have been a subject of debate over the last three to four decades. While there has been enough evidence of "no adverse observable" health effects at low doses and low dose rates, the hypothesis of "Linear No Threshold" continues to rule and govern the principles of radiation protection and the formulation of regulations and public policies. In adopting this conservative approach, the role of the biological processes underway in the human body is kept at abeyance. This review consolidates the available studies that discuss all related biological pathways and repair mechanisms that inhibit the progression of deleterious effects at low doses and low dose rates of ionizing radiation. It is pertinent that, taking cognizance of these processes, there is a need to have a relook at policies of radiation protection, which as of now are too stringent, leading to undue economic losses and negative public perception about radiation.

Adaptation of sea turtles to climate warming: Will phenological responses be sufficient to counteract changes in reproductive output?

Sea turtles are vulnerable to climate change since their reproductive output is influenced by incubating temperatures, with warmer temperatures causing lower hatching success and increased feminization of embryos. Their ability to cope with projected increases in ambient temperatures will depend on their capacity to adapt to shifts in climatic regimes. Here, we assessed the extent to which phenological shifts could mitigate impacts from increases in ambient temperatures (from 1.5 to 3°C in air temperatures and from 1.4 to 2.3°C in sea surface temperatures by 2100 at our sites) on four species of sea turtles, under a "middle of the road" scenario (SSP2-4.5). Sand temperatures at sea turtle nesting sites are projected to increase from 0.58 to 4.17°C by 2100 and expected shifts in nesting of 26-43 days earlier will not be sufficient to maintain current incubation temperatures at 7 (29%) of our sites, hatching success rates at 10 (42%) of our sites, with current trends in hatchling sex ratio being able to be maintained at half of the sites. We also calculated the phenological shifts that would be required (both backward for an earlier shift in nesting and forward for a later shift) to keep up with present-day incubation temperatures, hatching success rates, and sex ratios. The required shifts backward in nesting for incubation temperatures ranged from -20 to -191 days, whereas the required shifts forward ranged from +54 to +180 days. However, for half of the sites, no matter the shift the median incubation temperature will always be warmer than the 75th percentile of current ranges. Given that phenological shifts will not be able to ameliorate predicted changes in temperature, hatching success and sex ratio at most sites, turtles may need to use other adaptive responses and/or there is the need to enhance sea turtle resilience to climate warming.

Quercetin induces its chemoprotective effects via hormesis.

Quercetin is a polyphenol present in numerous fruits and vegetables and therefore widely consumed by humans with average daily dietary intakes of 10-20 mg/day. It is also a popular dietary supplement of 250-1000 mg/day. However, despite the widespread consumer interest in quercetin, due to its possible chemopreventive properties, the extensively studied quercetin presents a highly diverse and complex array of biological effects. Consequently, the present paper provides the first assessment of quercetin-induced hormetic concentration/dose responses, their quantitative features and mechanistic foundations, and their biological, biomedical, clinical, and public health implications. The findings indicate that quercetin-induced hormetic dose responses are widespread, being independent of biological model, cell type, and endpoint. These findings have the potential to enlighten future experimental studies with quercetin especially with respect to study design parameters and may also affect the appraisal of possible public health benefits and risks associated with highly diverse consumer consumption practices.

Quantification of Bile Acids in Cerebrospinal Fluid: Results of an Observational Trial.

(1) Background: Bile acids, known as aids in intestinal fat digestion and as messenger molecules in serum, can be detected in cerebrospinal fluid (CSF), although the blood-brain barrier is generally an insurmountable obstacle for bile acids. The exact mechanisms of the occurrence, as well as possible functions of bile acids in the central nervous system, are not precisely understood. (2) Methods: We conducted a single-center observational trial. The concentrations of 15 individual bile acids were determined using an in-house LC-MS/MS method in 54 patients with various acute and severe disorders of the central nervous system. We analyzed CSF from ventricular drainage taken within 24 h after placement, and blood samples were drawn at the same time for the presence and quantifiability of 15 individual bile acids. (3) Results: At a median time of 19.75 h after a cerebral insult, the concentration of bile acids in the CSF was minute and almost negligible. The CSF concentrations of total bile acids (TBAs) were significantly lower compared to the serum concentrations (serum 0.37 µmol/L [0.24, 0.89] vs. 0.14 µmol/L [0.05, 0.43]; p = 0.033). The ratio of serum-to-CSF bile acid levels calculated from the respective total concentrations were 3.10 [0.94, 14.64] for total bile acids, 3.05 for taurocholic acid, 14.30 [1.11, 27.13] for glycocholic acid, 0.0 for chenodeoxycholic acid, 2.19 for taurochenodeoxycholic acid, 1.91 [0.68, 8.64] for glycochenodeoxycholic acid and 0.77 [0.0, 13.79] for deoxycholic acid; other bile acids were not detected in the CSF. The ratio of CSF-to-serum S100 concentration was 0.01 [0.0, 0.02]. Serum total and conjugated (but not unconjugated) bilirubin levels and serum TBA levels were significantly correlated (total bilirubin p = 0.031 [0.023, 0.579]; conjugated bilirubin p = 0.001 [0.193, 0.683]; unconjugated p = 0.387 [-0.181, 0.426]). No correlations were found between bile acid concentrations and age, delirium, intraventricular blood volume, or outcome measured on a modified Rankin scale. (4) Conclusions: The determination of individual bile acids is feasible using the current LC-MS/MS method. The results suggest an intact blood-brain barrier in the patients studied. However, bile acids were detected in the CSF, which could have been achieved by active transport across the blood-brain barrier.

Quantum Biology and the Potential Role of Entanglement and Tunneling in Non-Targeted Effects of Ionizing Radiation: A Review and Proposed Model.

It is well established that cells, tissues, and organisms exposed to low doses of ionizing radiation can induce effects in non-irradiated neighbors (non-targeted effects or NTE), but the mechanisms remain unclear. This is especially true of the initial steps leading to the release of signaling molecules contained in exosomes. Voltage-gated ion channels, photon emissions, and calcium fluxes are all involved but the precise sequence of events is not yet known. We identified what may be a quantum entanglement type of effect and this prompted us to consider whether aspects of quantum biology such as tunneling and entanglement may underlie the initial events leading to NTE. We review the field where it may be relevant to ionizing radiation processes. These include NTE, low-dose hyper-radiosensitivity, hormesis, and the adaptive response. Finally, we present a possible quantum biological-based model for NTE.

Immune status of people living in the Tande-Tande sub-village (Indonesia), an area with high indoor radon concentration.

On Earth, there are significant variations in terms of exposure to naturally occurring radiation among different areas. Radon, a naturally-occurring radioactive gas that is the primary cause of lung cancer in nonsmokers and the second most prevalent cause among smokers, poses a considerable risk. Indoor radon, in particular, constitutes the most substantial source of natural radiation to which individuals are exposed. This study assessed the immune status of a population chronically exposed to high indoor radon concentration in Indonesia. Fifty-seven subjects from the Tande-Tande sub-village (high indoor radon concentration area) were compared to fifty-three participants living in the Topoyo village (low concentration area). We contrasted the immunological conditions of these two populations by measuring levels of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-4 (IL-4), and IL-10 in serum. Moreover, we also measured levels of the nuclear factor kappa B (NF-κB), superoxide dismutase (SOD), glutathione peroxidase (GPX), and protein kinase B in its phosphorylated (pAkt) and non-phosphorylated form (Akt) in peripheral blood mononuclear cells (PBMCs) of a subset of participants (31 from each population). TNF-α, IFN-γ, and IL-4 levels in Tande-Tande sub-village inhabitants were significantly lower than those in the control group living in the Topoyo village (p = 0.001, p = 0.017, and p = 0.002). The concentration of IL-10 also tended to be lower in people living in the high indoor radon concentration area, but it did not differ significantly between Tande-Tande sub-village inhabitants and Topoyo inhabitants (p = 0.106). Protein levels of NF-κB, pAkt, and Akt in Tande-Tande sub-village inhabitants also did not differ significantly between Tande-Tande sub-village inhabitants and Topoyo inhabitants (p = 0.234, p = 0.210, and p = 0.657). Similarly, activities of SOD and GPX did not differ significantly between the two populations (p = 0.569 and p = 0.949). Overall, despite their chronic exposure to high indoor radon concentrations, our study revealed no increase in the levels of TNF-α, IFN-γ, IL-10, IL-4, SOD, and GPX in the inhabitants of Tande-Tande sub-village compared with people living in the Topoyo village. Furthermore, our study demonstrated no activation in the Akt pathway, as indicated by the pAkt/Akt ratio observed in PBMC lysates of individuals residing in the Tande-Tande sub-village.

Rabbits as Animal Models for Anti-Tick Vaccine Development: A Global Scenario.

Studies evaluating candidate tick-derived proteins as anti-tick vaccines in natural hosts have been limited due to high costs. To overcome this problem, animal models are used in immunization tests. The aim of this article was to review the use of rabbits as an experimental model for the evaluation of tick-derived proteins as vaccines. A total of 57 tick proteins were tested for their immunogenic potential using rabbits as models for vaccination. The most commonly used rabbit breeds were New Zealand (73.8%), Japanese white (19%), Californians (4.8%) and Flemish lop-eared (2.4%) rabbits. Anti-tick vaccines efficacy resulted in up to 99.9%. Haemaphysalis longicornis (17.9%) and Ornithodoros moubata (12.8%) were the most common tick models in vaccination trials. Experiments with rabbits have revealed that some proteins (CoAQP, OeAQP, OeAQP1, Bm86, GST-Hl, 64TRP, serpins and voraxin) can induce immune responses against various tick species. In addition, in some cases it was possible to determine that the vaccine efficacy in rabbits was similar to that of experiments performed on natural hosts (e.g., Bm86, IrFER2, RmFER2, serpins and serine protease inhibitor). In conclusion, results showed that prior to performing anti-tick vaccination trials using natural hosts, rabbits can be used as suitable experimental models for these studies.

Adaptive response of triploid Fujian oyster (Crassostrea angulata) to nanoplastic stress: Insights from physiological, metabolomic, and microbial community analyses.

Triploid Fujian oyster (Crassostrea angulata) is crucial to aquaculture and coastal ecosystems because of its accelerated growth and heightened resilience against environmental stressors. In light of the increasing prevalence of nanoplastic pollution in the ocean, understanding its potential impact on this organism, particularly its adaptive responses, is of paramount importance. Despite this, the effects of nanoplastic pollution on the physiology of C. angulata remain largely unexplored. In this study, we explored the responses of triploid Fujian oysters to nanoplastic stress during a 14-day exposure period, employing an integrative methodology that included physiological, metabolomic, and 16S rRNA sequencing analyses. Our results demonstrate that the oysters exhibit a strong adaptive response to nanoplastic exposure, characterized by alterations in enzyme activity, metabolic pathways, and microbial community composition, indicative of an adaptive recovery state as opposed to a disordered state. Oysters subjected to elevated nanoplastic levels exhibited adaptive responses primarily by boosting the activity of the antioxidant enzyme catalase and elevating the levels of antioxidants such as adenosine, 3-(4-hydroxyphenyl)pyruvate, D-sorbitol, d-mannose, and unsaturated fatty acids, as well as the functional amino acids l-proline and l-lysine. Nanoplastic treatment also resulted in increased activity of succinate dehydrogenase, a key component of energy metabolism, and increased contents of intermediate metabolites or products of energy metabolism, such as adenosine monophosphate, adenosine, guanosine, creatine, and thiamine. Nanoplastic treatment led to an increase in the abundance of certain advantageous genera of gut bacteria, specifically Phaeobacter and Nautella. The observed adaptive response of triploid Fujian oysters to nanoplastic stress provides valuable insights into the mechanisms underpinning resilience in marine bivalves.

Sigma factors of RNA polymerase in the pathogenic spirochaete Leptospira interrogans, the causative agent of leptospirosis.

The aim of this review is to summarize the current knowledge on the role of σ factors in a highly invasive spirochaete Leptospira interrogans responsible for leptospirosis that affects many mammals, including humans. This disease has a significant impact on public health and the economy worldwide. In bacteria, σ factors are the key regulators of gene expression at the transcriptional level and therefore play an important role in bacterial adaptative response to different environmental stimuli. These factors form a holoenzyme with the RNA polymerase core enzyme and then direct it to specific promoters, which results in turning on selected genes. Most bacteria possess several different σ factors that enable them to maintain basal gene expression, as well as to regulate gene expression in response to specific environmental signals. Recent comparative genomics and in silico genome-wide analyses have revealed that the L. interrogans genome, consisting of two circular chromosomes, encodes a total of 14 σ factors. Among them, there is one putative housekeeping σ70 -like factor, and three types of alternative σ factors, i.e., one σ54 , one σ28 and 11 putative ECF (extracytoplasmic function) σE -type factors. Here, characteristics of these putative σ factors and their possible role in the L. interrogans gene regulation (especially in this pathogen's adaptive response to various environmental conditions, an important determinant of leptospiral virulence), are presented.

Overexpression of CD99 is associated with tumor adaptiveness and indicates the tumor recurrence and therapeutic responses in gliomas.

Glioma undergoes adaptive changes, leading to poor prognosis and resistance to treatment. CD99 influences the migration and invasion of glioma cells and plays an oncogene role. However, whether CD99 can affect the adaptiveness of gliomas is still lacking in research, making its clinical value underestimated. Here, we enrolled our in-house and public multiomics datasets for bioinformatic analysis and conducted immunohistochemistry staining to investigate the role of CD99 in glioma adaptive response and its clinical implications. CD99 is expressed in more adaptative glioma subtypes and cell states. Under hypoxic conditions, CD99 is upregulated in glioma cells and is associated with angiogenesis and metabolic adaptations. Gliomas with over-expressed CD99 also increased the immunosuppressive tumor-associated macrophages. The relevance with tumor adaptiveness of CD99 presented clinical significance. We discovered that CD99 overexpression is associated with short-time recurrence and validated its prognostic value. Additionally, Glioma patients with high expression of CD99 were resistant to chemotherapy and radiotherapy. The CD99 expression was also related to anti-angiogenic and immune checkpoint inhibitor therapy response. Inhibitors of the PI3K-AKT pathway have therapeutic potential against CD99-overexpressing gliomas. Our study identified CD99 as a biomarker characterizing the adaptive response in glioma. Gliomas with high CD99 expression are highly tolerant to stress conditions such as hypoxia and antitumor immunity, making treatment responses dimmer and tumor progression. Therefore, for patients with CD99-overexpressing gliomas, tumor adaptiveness should be fully considered during treatment to avoid drug resistance, and closer clinical monitoring should be carried out to improve the prognosis.

Low-Dose Non-Targeted Effects and Mitochondrial Control.

Non-targeted effects (NTE) have been generally regarded as a low-dose ionizing radiation (IR) phenomenon. Recently, regarding long distant abscopal effects have also been observed at high doses of IR) relevant to antitumor radiation therapy. IR is inducing NTE involving intracellular and extracellular signaling, which may lead to short-ranging bystander effects and distant long-ranging extracellular signaling abscopal effects. Internal and "spontaneous" cellular stress is mostly due to metabolic oxidative stress involving mitochondrial energy production (ATP) through oxidative phosphorylation and/or anaerobic pathways accompanied by the leakage of O2- and other radicals from mitochondria during normal or increased cellular energy requirements or to mitochondrial dysfunction. Among external stressors, ionizing radiation (IR) has been shown to very rapidly perturb mitochondrial functions, leading to increased energy supply demands and to ROS/NOS production. Depending on the dose, this affects all types of cell constituents, including DNA, RNA, amino acids, proteins, and membranes, perturbing normal inner cell organization and function, and forcing cells to reorganize the intracellular metabolism and the network of organelles. The reorganization implies intracellular cytoplasmic-nuclear shuttling of important proteins, activation of autophagy, and mitophagy, as well as induction of cell cycle arrest, DNA repair, apoptosis, and senescence. It also includes reprogramming of mitochondrial metabolism as well as genetic and epigenetic control of the expression of genes and proteins in order to ensure cell and tissue survival. At low doses of IR, directly irradiated cells may already exert non-targeted effects (NTE) involving the release of molecular mediators, such as radicals, cytokines, DNA fragments, small RNAs, and proteins (sometimes in the form of extracellular vehicles or exosomes), which can induce damage of unirradiated neighboring bystander or distant (abscopal) cells as well as immune responses. Such non-targeted effects (NTE) are contributing to low-dose phenomena, such as hormesis, adaptive responses, low-dose hypersensitivity, and genomic instability, and they are also promoting suppression and/or activation of immune cells. All of these are parts of the main defense systems of cells and tissues, including IR-induced innate and adaptive immune responses. The present review is focused on the prominent role of mitochondria in these processes, which are determinants of cell survival and anti-tumor RT.

Diagnostic low-dose X-ray radiation induces fluoroquinolone resistance in pathogenic bacteria.

PURPOSE: The crisis of antibiotic resistance has been attributed to the overuse or misuse of these medications. However, exposure of bacteria to physical stresses such as X-ray radiation, can also lead to the development of resistance to antibiotics. The present study aimed to investigate the effect of exposure to diagnostic low-dose X-ray radiation on the bacterial response to antibiotics in two pathogenic bacteria, including the Gram-positive Staphylococcus aureus and Gram-negative Salmonella enteritidis. METHODS: The bacterial strains were exposed to diagnostic X-ray doses of 5 and 10 mGy, which are equivalent to the doses delivered to patients during conventional radiography X-ray examinations in accordance with the European guidelines on quality criteria for diagnostic radiographic images. Following exposure to X-ray radiation, the samples were used to estimate bacterial growth dynamics and perform antibiotic susceptibility tests. RESULTS: The results indicate that exposure to diagnostic low-dose X-ray radiation increased the number of viable bacterial colonies of both Staphylococcus aureus and Salmonella enteritidis and caused a significant change in bacterial susceptibility to antibiotics. For instance, in Staphylococcus aureus, the diameter of the inhibition zones for marbofloxacin decreased from 29.66 mm before irradiation to 7 mm after irradiation. A significant decrease in the inhibition zone was also observed for penicillin. In the case of Salmonella enteritidis, the diameter of the inhibition zone for marbofloxacin was 29 mm in unexposed bacteria but decreased to 15.66 mm after exposure to 10 mGy of X-ray radiation. Furthermore, a significant decrease in the inhibition zone was detected for amoxicillin and amoxicillin/clavulanic acid (AMC). CONCLUSION: It is concluded that exposure to diagnostic X-ray radiation can significantly alter bacterial susceptibility to antibiotics. This irradiation decreased the effectiveness of fluoroquinolone and ß-lactam antibiotics. Specifically, low-dose X-rays made Staphylococcus aureus resistant to marbofloxacin and increased its resistance to penicillin. Similarly, Salmonella Enteritidis became resistant to both marbofloxacin and enrofloxacin, and showed reduced sensitivity to amoxicillin and AMC.

Comparative study of the digestion and metabolism related genes' expression changes during the postnatal food change in different dietary mammals.

The changes in the expression of genes related to digestion and metabolism may be various in different dietary mammals from juvenile to adult, especially, the giant panda (Ailuropoda melanoleuca) and red panda (Ailurus fulgens), which were once carnivores but have shifted to being specialized bamboo eaters, are unique features of their changes are more unclear. To elucidate the changing patterns of gene expression related to digestion and metabolism from juvenile to adult in different dietary mammals, we performed transcriptome analysis of the liver or pancreas in giant and red pandas, herbivorous rabbits (Oryctolagus cuniculus) and macaques (Macaca mulatta), carnivorous ferrets (Mustela putorius furo), and omnivorous mice (Mus musculus) from juvenile to adult. During the transition from juvenile to adulthood, giant and red pandas, as well as rabbits and macaques, show significant upregulation of key genes for carbohydrate metabolism, such as starch hydrolysis and sucrose metabolism, and unsaturated fatty acid metabolism, such as linoleic acid, while there is no significant difference in the expression of key genes for fatty acid ß-oxidation. A large number of amino acid metabolism related genes were upregulated in adult rabbits and macaques compared to juveniles. While adult giant and red pandas mainly showed upregulation of key genes for arginine synthesis and downregulation of key genes for arginine and lysine degradation. In adult stages, mouse had significantly higher expression patterns in key genes for starch hydrolysis and sucrose metabolism, as well as lipid and protein metabolism. In contrast to general expectations, genes related to lipid, amino acid and protein metabolism were significantly higher expressed in adult group of ferrets, which may be related to their high metabolic levels. Our study elucidates the pattern of changes in the expression of genes related to digestion and metabolism from juvenile to adult in different dietary mammals, with giant and red pandas showing adaptations associated with specific nutritional limitations of bamboo.