In the current radiation protection system, preventive measures and occupational exposure limits for controlling occupational exposure to ionizing radiation are based on the linear no-threshold extrapolation model. However, currently an increasing body of evidence indicates that this paradigm predicts very poorly biological responses in the low-dose exposure region. In addition, several in vitro and in vivo studies demonstrated the presence of hormetic dose response curves correlated to ionizing radiation low exposure. In this regard, it is noteworthy that also the findings of different epidemiological studies, conducted in different categories of occupationally exposed workers (e.g., healthcare, nuclear industrial and aircrew workers), observed lower rates of mortality and/or morbidity from cancer and/or other diseases in exposed workers than in unexposed ones or in the general population, then suggesting the possible occurrence of hormesis. Nevertheless, these results should be considered with caution since the identification of hormetic response in epidemiological studies is rather challenging because of a number of major limitations. In this regard, some of the most remarkable shortcomings found in epidemiological studies performed in workers exposed to ionizing radiation are represented by lack or inadequate definition of exposure doses, use of surrogates of exposure, narrow dose ranges, lack of proper control groups and poor evaluation of confounding factors. Therefore, considering the valuable role and contribution that epidemiological studies might provide to the complex risk assessment and management process, there is a clear and urgent need to overcome the aforementioned limits in order to achieve an adequate, useful and more real-life risk assessment that should also include the key concept of hormesis. Thus, in the present conceptual article we also discuss and provide possible approaches to improve the capacity of epidemiological studies to identify/define the hormetic response and consequently improve the complex process of risk assessment of ionizing radiation at low exposure doses.

Hormesis is a biphasic dose-response relationship featured by low-dose stimulation and high-dose inhibition. Although the hormetic phenomenon has been extensively studied over the past decades, there is little information regarding the influence of energy source on the occurrence of hormesis, especially the time-dependent one. In this study, to explore the role of cultivation system\'s energy source in time-dependent hormesis, the toxic dose-responses of Aliivibrio fischeri (A. fischeri) bioluminescence to Sulfadoxine (SDX) during 24 h were determined in four cultivation systems with different energy source conditions. The results indicated that the time-dependent hormetic effects were induced by SDX in all cultivation systems: SDX triggered hormetic phenomenon on the bioluminescence at each growth stage over 24 h in the cultivation systems with sufficient and insufficient energy source; due to the diauxic growth of A. fischeri under multiple energy source conditions, the hormetic effects of SDX gradually disappeared after the preferred energy source was used up. It was speculated that the inhibitory action of SDX was derived from its interaction with DHPS to impede the synthesis of proteins, and SDX bound with AC to upregulate the quorum sensing (QS) system to exhibit the stimulatory action. Comparing the time-dependent hormesis in each cultivation system, it was obtained that the energy source could impact the hourly maximum stimulatory rate, the EC50 of SDX, and the time point that hormesis occurred, which might result from the influence of energy source on the stimulatory and inhibitory actions of SDX through regulating the metabolic system (individual level) and QS system (group level) of bacteria. This study clarifies the importance of energy source for hormesis occurrence, which may further promote the development of hormesis.

Skin aging is primarily associated with the alterations in dermal extracellular matrix, in particular a decrease in collagen type-1 content. Recent studies have shown that collagen-degrading matrix metalloproteinase (MMP-1) is produced by fibroblasts in response to chronoaging, which in human dermal fibroblasts leads to the release of proinflammatory cytokines. Past studies showed that anti-inflammatory capabilities could be induced via non-chemical means. One of these methods makes use of ultra-weak fractal electromagnetic (uwf-EM) signals. Such ultra-/very-low frequency (U/VLF) signals (few nT in intensity and within 0.5-30 kHz) interact with aqueous solutions in living systems. The fractal nature of such EM-signals relates to the self-similar property by which a \"cut-out\" and magnified piece of this signal reveals again the original. Thus, the aim of this study is twofold, to i) investigate the extent of this modulating effect using Human Dermal Fibroblasts (HDF)-cells, and ii) analyse molecular rejuvenation markers therein. We could demonstrate that a 10 min uwf-EM exposure (prior to incubation) increases type-1 collagen and modulates elastin in human fibroblasts cultured up to 96 h, while at the same time reduces IL-6, TNF-α and MMP-1 (the later three being statistically significant). Such up- respectively down-regulation of corresponding genes are strong indicators of an EM-induced hormetic effect that influences the epigenomic landscape of HDFs. In the Appendix, we present, in the framework of Quantum Field Theory (QFT), water as a biphasic liquid and how its coherent fraction can be affected by uwf-EM signals while at the same time resolving the \"kT paradox\".

BACKGROUND: It is well known that exposure to mild stress can precondition organisms to better tolerate subsequent stress exposure in the same or future generations. Since herbicide hormesis also represents a moderate stress to exposed plants, a transgenerational priming is likely but not proven. Especially in herbicide-resistant weeds showing enhanced reproductive fitness after regular herbicide treatments, the ability to induce resilient offspring phenotypes via hormesis may hasten the evolution of herbicide resistance in weeds. This hypothesis was studied for the triazinone metamitron in an F1 offspring generation of PSII target-site resistant (TSR) plants of Chenopodium album propagated after parental conditioning with various metamitron doses.
RESULTS: In two independent dose-response greenhouse trials, there was a positive correlation between the strength of the stimulatory response during parental preconditioning and the magnitude of transgenerational changes in herbicide sensitivity and hormesis expression. Parental conditioning at subhormetic and toxic concentrations lead to less resilient offspring, while conditioning doses that induced a pronounced hormetic effect in F0 plants had a sensitivity-reducing and hormesis-promoting effect on the offspring. The observed reduction in sensitivity in F1 plants compared to unconditioned F1 plants was up to 2.2-fold.
CONCLUSIONS: This study demonstrates that hormetic herbicide treatments have the ability to prime weeds for enhanced tolerance to subsequent treatments in the next generation. Effects proved dose sensitive and may act in concert with other stimulatory adaptations in plant populations. This is relevant for weed control and herbicide resistance evolution, but also for herbicide side-effects that go beyond the exposed area. © 2020 The Author. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Time-dependent cross-phenomenon in which the cross between the actual concentration-response curve (CRC) for mixture crosses the CRCs for reference model varies with time has been frequently reported in previous studies, expressed as a heterogeneous pattern of joint toxic action. However, the variation tendency of time-dependent cross-phenomenon is rarely addressed. In this study, the joint toxic actions of binary antibacterial mixtures (i.e., two quorum sensing inhibitors, tetracycline hydrochloride, erythromycin, and chloramphenicol with sulfonamides) were judged using independent action (IA) model to find the variation tendency of time-dependent cross-phenomenon. The results show that the time-dependent cross-phenomena of the test binary antibacterial mixtures follow a unified variation tendency and the corresponding joint toxic actions change regularly with an increase of both concentration and time. Through investigating the relationship between the stimulatory and inhibitory modes of action for the single agents and the time-dependent cross-phenomena of binary mixtures, the regular time-dependent cross-phenomena is speculated to be derived from the hormetic effects of the components in the mixtures. This study offers an advance for the variation tendency and mechanistic explanation of time-dependent cross-phenomenon, which will provide a support for the future development in the exploration of time-dependent cross-phenomenon and environmental risk assessment of pollutant mixtures.

Numerous intentionally released toxins persist in agricultural or natural environments at low concentrations. Such low toxin doses are regularly associated with hormesis, i.e., growth stimulation, and they are suspected to affect mortality and within-population plant size distribution in dense plant stands. However, it is not known whether all these low-dose effects exist when plants grow in soil. We exposed barley to a range of low glyphosate doses and let the plants grow in dense stands for several weeks in soil. Six experiments were done that contained altogether 10,260 seedlings in 572 pots. We evaluated if the changes in average biomass and shoot length occur at the same concentrations as do the effects on slow- and fast-growing individuals, if seed size or early vigor explains variation in the response to glyphosate, and if low toxin doses change within-population mortality. Plant biomass, length and survival of subpopulations changed at doses that did not affect mean biomass. Effects of early vigor faded early, but differences in seed size and particularly vegetative growth had impacts: fast-growing plants hardly showed hormesis, whereas hormesis was particularly strong among slow-growing individuals. Compared to the population mean, glyphosate effects started at lower doses among slow-growing individuals and at higher doses among fast-growing individuals. Several times higher doses were needed before the fast-growing individuals showed the same toxicity as most of the population. Low toxin doses regularly enhanced the growth of the smallest individuals, which reduced size variation within populations and was associated with a higher number of surviving plants. Indeed, in one experiment self-thinning was not observed at low doses that stimulated the growth of slow-growing plants. As glyphosate levels in this study match those observed in agricultural fields and natural environments, we conclude that even low-levels of agro-environmental contamination are likely to shape phenotypic response, which might lead to adaptation and cascading ecological impacts.

Hormesis is a dose-response relationship phenomenon characterized by low-dose stimulation and high-dose inhibition. Although hormetic phenomena have been reported in broadly ranging biological areas, there is still no unified mechanism of hormesis. Investigating multiple-species hormesis of one compound and then exploring the possible mechanism may be an effective approach to clarify the reason for the occurrence of hormetic phenomena in a broad range of organisms. In this study, indole was selected as the test chemical due to the broad biological and hormetic effects of indole compounds. The results show that indole induces multiple-species hormetic phenomena in bacteria (Aliivibrio fischeri (A. fischeri), Escherichia coli and Bacillus subtilis), algae (Microcystis aeruginosa and Selenastrum capricornutum), and human cells (human skin fibroblasts and human cervical cancer cells). Through in-depth investigation of the time-dependent hormetic effects of indole, indole derivatives and indole\'s structural analogs on the bioluminescence of A. fischeri, indole ring has been identified as the potential key structure that causes indole to act on quorum sensing of A. fischeri to induce hormetic effects on the bioluminescence at lag, logarithmic, and stationary phases. Therefore, the occurrence of multiple-species hormetic phenomena is speculated to be derived from the action of indole on the cell-to-cell communication of organism cells. This paper can not only further confirm the generalizability of hormesis but also provide a reasonable explanation for hormesis, which will benefit the development of hormesis and the risk assessment of environmental pollutants.

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that occurs commonly in old people. Hot spring radon therapy is widely practiced in Central Europe and Japan for relief from the painful symptoms. The usual duration of a spa treatment is a week or two, and the relief is temporary. This article reports on the near-complete recovery of a patient who had been suffering from RA for 10 years. The patient received 15 months of low-dose radon and γ-radiation therapy in a room that reproduced the conditions of a radon spa. The daily 40-minute exposure in the therapy room was supplemented by ten 6-minute radio-nebulizer treatments. The inflammation markers C-reactive protein and matrix metalloproteinase 3 declined strongly to the normal level of 0.07 mg/dL and the near-normal level of 48.9 ng/mL, respectively. After the patient\'s return to good health, the frequency of the visits was reduced to twice each month. The patient\'s protection systems appear to have adapted to stimulated conditions, sufficiently to sustain the recovery from RA. Such a long-term course of treatments and follow-up maintenance could be carried out in any hospital that has these low-dose radiation therapy rooms. The therapy could be scheduled to suit patient availability.

BACKGROUND: Herbicide hormesis may play a role in the evolution of weed resistance by increasing resistance selection. A standard herbicide rate may be subtoxic to resistant plants and make them more fit than untreated plants. If this increase in fitness is ultimately expressed in reproductive traits, resistance genes can accumulate more rapidly and exacerbate resistance evolution by magnifying the selection differential between resistant and sensitive plants. The hypothesis of hormetically enhanced reproductive fitness was studied for a photosystem II (PSII) target-site resistant (TSR) biotype of Chenopodium album exposed to the triazinone metamitron in comparison with its wild-type.
RESULTS: Both biotypes showed an initial hormetic growth increase at different doses leading to fitness enhancements of between 19% and 61% above untreated plants. However, hormetic effects only resulted in higher fitness at maturity in resistant plants with a maximum stimulation in seed yield of 45% above untreated plants. Applying realistic metamitron rates, reproductive fitness of resistant plants was increased by 15-32%.
CONCLUSIONS: Agronomically relevant doses of metamitron induced considerable hormesis in a PSII-TSR C. album genotype leading to enhanced relative fitness through reproductive maturity. This increase in relative fitness suggests an impact on resistance selection and can compensate for the oft-reported fitness costs of the mutation studied. Field rates of herbicides can, thus, not only select for resistant plants, but also enhance their reproductive fitness. The finding that herbicide hormesis can be eco-evolutionary important may have important implications for understanding the evolution of herbicide resistance in weeds. © 2018 Society of Chemical Industry.

Hormesis occurs frequently in broadly ranging biological areas (e.g. plant biology, microbiology, biogerontology), toxicology, pharmacology and medicine. While numerous mechanisms (e.g. receptor and pathway mediated pathway responses) account for stimulatory and inhibitory features of hormetic dose responses, the vast majority emphasizes the inclusion of many doses but only one timepoint or use of a single optimized dose that is assessed over a broad range of timepoints. In this paper, a toxicity study was designed using a large number of properly spaced doses with responses determined over a large number of timepoints, which could help us reveal the underlying mechanism of hormesis. We present the results of a dose-time-response study on hormesis using five antibacterial chemicals on the bioluminescence of Aliivibrio fischeri, measuring expression of protein mRNA based on quorum sensing, simulating bioluminescent reaction and analyzing toxic actions of test chemicals. The findings show dose-time-dependent responses conforming to the hormetic dose-response model, while revealing unique response dynamics between agent induced stimulatory and inhibitory effects within bacterial growth phase dynamics. These dynamic dose-time features reveal a type of biological seesaw model that integrates stimulatory and inhibitory responses within unique growth phase, dose and time features, which has faultlessly explained the time-dependent hormetic phenomenon induced by five antibacterial chemicals (characterized by low-dose stimulation and high-dose inhibition). This study offers advances in understanding cellular dynamics, the biological integration of diverse and opposing responses and their role in evolutionary adaptive strategies to chemicals, which can provide new insight into the mechanistic investigation of hormesis.