Bystander Effect Research Papers - Academia.edu (original) (raw)

2025, The Journal of Immunology

T cell proliferation and survival are regulated by the cytokine receptor common γ-chain-associated cytokines IL-2, IL-7, and IL-15, while IL-4, another γ-chain-associated cytokine, is thought to primarily affect T cell quality rather than quantity. In contrast, our experiments reveal that endogenously produced IL-4 is a direct, nonredundant, and potent stimulator of CD8+ T cell proliferation in Ag- and pathogen-induced CD8+ T cell responses. These stimulatory effects of IL-4 are observed in both BALB/c and C57BL/6 mice and activate both naive and memory/activated phenotype CD8+ T cells, although the former are stimulated less than are the latter. IL-4 effects are IL-7- and IL-15-independent, but MHC class I-dependent stimulation appears to be required for the mitogenic effect of IL-4 on naive phenotype CD8+ T cells. Thus, endogenously produced IL-4 is an important regulator of quantitative as well as qualitative aspects of T cell immunity.

2025, Journal of King Abdulaziz University-Medical Sciences

This work aims at determining the difference of proinflammatory cytokines, adhesion molecules in synovial fluid, serum of rheumatoid arthritis, osteoarthritis patients Synovial fluid and serum were obtained from rheumatoid arthritis (n = 21), osteoarthritis (n = 11) patients, serum of healthy individuals (n = 12). Interleukin-1β, tumor necrosis factor-alpha, sE-selectin levels were measured by Enzyme-Linked Immunosorbent Assay Test. Compared to controls, S-sE-selectin was significantly elevated in rheumatoid arthritis while S-IL-1β, S-TNF-α were elevated in rheumatoid arthritis and osteoarthritis patients. S-sE-selectin, SF-IL-1β and SF-TNF-α were significantly elevated in rheumatoid arthritis versus osteoarthritis. In rheumatoid arthritis, SF-sE-selectin was significantly lower while SF-TNF-α was higher than serum in rheumatoid arthritis and osteoarthritis. In rheumatoid arthritis, positive correlation between SF-E-selectin with serum -C-reactive Protein and S-sE-selectin; between S-sE-selectin with disease duration and S-TNF-α; between S-IL1-β with SF-IL1-β and disease activity while negative correlationbetween S-TNF-α with grip strength were found. A degree of vascular endothelial activation reflected by increased sE-selectin, is associated with disease activity, duration in rheumatoid arthritis. The positive association between IL-1β, disease activity and negative association between TNF-α, grip strength indicated that serial estimation of these cytokines may be used to monitor disease progression. Elevated TNFα in synovial fluid than in serum of rheumatoid arthritis, osteoarthritis patients indicates its local formation in the synovium.

2025, Physics in Medicine and Biology

The authors of a recent paper (Claridge Mackonis et al 2007 Phys. Med. Biol. 52 5469-82) measured cell survival in spatially modulated radiation fields. They claim to have identified two new types of radiation-induced bystander effect. We... more

2025, Computers in Human Behavior

This study aims to investigate whether student bystander interventions can influence the relationship between being a bystander of a cyberbullying incident and being the victim or the aggressor. Another aim is to understand the specific behavior presented by students bystanders, namely whether they noticed incidents of cyberbullying and interpreted these events as an emergency and which actions they determined as being appropriate in providing assistance. Following a cross-cultural perspective to reach these aims, a total of 788 Portuguese and Brazilian college students answered to the Cyberbullying Inventory for College Students. Moderation analysis revealed that intervening moderated the relationship between being the bystander of cyberbullying and being the victim and/or aggressor. A three-way interaction showed that this relationship was stronger in Brazilian students, revealing that the bystanders who were inactive were more likely to also become a victim or an aggressor themselves, whereas those who intervened were less likely to become a victim or an aggressor. Implications for future research and interventive action are discussed.

2025, Sex Roles

Sexual assault is a common phenomenon on university campuses with about one in five women victimized while in college. Consequently, bystander intervention programs have been gaining momentum. To improve such programs, research has begun to identify factors that may facilitate or impede individuals' willingness to help a potential victim of sexual assault. The current study adds to this literature by: (a) examining potential differences in rape myth acceptance, critical consciousness, and willingness to help based on types of self-reported exposure to sexual assault; (b) exploring the previously unexamined mediating role of critical consciousness in the relationship between exposure to sexual assault and willingness to help; and (c) clarifying how the extent of rape myth acceptance impacts the relationship between exposure to sexual assault and willingness to help. Using a sample of 511 U.S. undergraduate students, results generally demonstrated that those with multiple types of exposure to sexual assault victimization demonstrated the highest levels of critical consciousness and greater willingness to help. Additionally, there was both a significant indirect effect of exposure to sexual assault on willingness to help via critical consciousness and a conditional effect of exposure to sexual assault on willingness to help that was stronger at lower levels of rape myth acceptance. Results highlight the importance of programming targeted at increasing critical consciousness.

2025, Sex Roles

2025, Journal of Community Psychology

The current study used an experimental design to evaluate a sexual violence prevention program based on a community of responsibility model that teaches women and men how to intervene safely and effectively in cases of sexual violence before, during, and after incidents with strangers, acquaintances, or friends. It approaches both women and men as potential bystanders or witnesses to behaviors related to sexual violence. Three hundred and eighty-nine undergraduates participated and were randomly assigned to one of two treatment groups or a control group. Results from the research reveal that up to 2 months after participating in either a one-or three-session version of the program, participants in the treatment conditions showed improvements across measures of attitudes, knowledge, and behavior while the control group did not. Most program effects persisted at 4-and 12-month follow-ups. The program appeared to benefit both women and men. Implications and future directions for research are discussed.

2025, Psychology of Violence

Objective: Two studies were conducted to (re)examine whether the strength differential hypothesis-that face-to-face bullies are likely to be physically stronger than victims-is valid in the cyberbullying domain. The novel contribution of our research includes testing the relations between the belief that strength is irrelevant for online bullying, online power (technological abilities), and cyberbullying within the theoretical integration of the Barlett and Gentile cyberbullying model and Bandura's self-efficacy theory. Method: Two studies had participant's complete measures of cyberbullying behavior, cyberbullying attitudes, online power, and the belief that strength is irrelevant for online bullying. Study 1 (N ϭ 147) utilized a cross-sectional design with a general adult population, whereas Study 2 (N ϭ 218) employed a short-term longitudinal study of college students. Results: Correlation and regression findings from Study 1 showed that (a) the belief that muscularity is irrelevant for online bullying (but not online power) was associated with more cyberbullying, and (b) this relation was mediated by cyberbullying attitudes. Study 2 replicated these results using a longitudinal path analysis. Conclusion: The current research supports the postulates of the BGCM by confirming the theoretically predicted relations between the belief that muscularity is irrelevant in the online world and cyberbullying behavior through the development of cyberbullying attitudes. Online power, in the form of computer skill, did not show this pattern, suggesting that perceptions of physical strength are more relevant even in the online world, supporting the original strength differential hypothesis.

2025, The Journal of Nuclear Medicine

2025, Radioprotection

In this paper our current knowledge of the mechanisms underlying the induction of bystander effects by low dose low LET ionizing radiation is reviewed in the context of relevance to radiation protection issues. The question of how bystander effects may be related to observed adaptive responses, systemic genomic instability or other effects of low doses exposures is also considered. Bystander effects appear to be the result of a generalized stress response in tissues or cells. The signals may be produced by all exposed cells, but the response may require additional system parameters to exist in order to be expressed. The major response involving low LET radiation exposure discussed in the existing literature is a death response. This can manifest as apoptotic cell death, terminal differentiation, reproductive cell death or necrosis. While a death response might appear to be adverse, the position is argued in this paper, that it can in fact be protective and remove damaged cells from the reproducing population. Since many cell populations carry damaged cells without being exposed to radiation (so-called "background damage"), it is possible that low dose radiation exposures cause removal of cells damaged by agents other than the test dose of radiation. This mechanism would lead to the production of "u-or nshaped" dose response curves. In this scenario, the level of harmful or beneficial response will be related to the background damage carried by the cell population and the genetic program determining response to damage. This model may be particularly important when attempting to predict the consequences of mixed exposures involving radiation and other environmental stressors on biota.

2025, Carcinogenesis

The existence of a bystander effect following both alpha and gamma irradiation of many cell lines is not now in dispute. The significance of this effect for cancer risk assessment and radiotherapy treatment planning requires demonstration of its relevance in vivo. The problem in demonstrating the existence of the effect in vivo is that other systemic effects may mask or confound the effect being investigated and it is practically impossible to attribute an effect in a particular cell to a signal produced in another irradiated cell. To approach this problem, we have developed an assay where fragments of human tissue can be irradiated ex vivo and the media harvested and added to unirradiated, allogenic explants or to a clonogenic cell line which has a well characterized and stable response to the bystander signal. The variation in production of the signal from patient to patient can thus be assessed using molecular and cellular endpoints. A study using tissue from over 100 patients and from mouse strains with well characterized responses to low level radiation exposure shows that there is variation in the effect of the signal produced by irradiated tissue from different patients. Gender, smoking status and the existence of a bladder malignancy influence the expression of the signal by normal urothelium. The effects of exposure to medium containing the signal are transmitted to distant progeny of the exposed cell population. The results may be important not only for understanding radiation risk mechanisms for protection but also for radiotherapy treatment planning where they may open new avenues for development of drugs for combined therapy.

2025, Cancers

Non-targeted effects (NTE) such as bystander effects or genomic instability have been known for many years but their significance for radiotherapy or medical diagnostic radiology are far from clear. Central to the issue are reported differences in the response of normal and tumour tissues to signals from directly irradiated cells. This review will discuss possible mechanisms and implications of these different responses and will then discuss possible new therapeutic avenues suggested by the analysis. Finally, the importance of NTE for diagnostic radiology and nuclear medicine which stems from the dominance of NTE in the low-dose region of the dose-response curve will be presented. Areas such as second cancer induction and microenvironment plasticity will be discussed.

2025, British Journal of Cancer

These experiments were done to determine if interference with energy metabolism and REDOX biochemistry during low LET radiation exposure would alter the ability of medium harvested from the irradiated cells to induce a bystander effect in unirradiated cells. Human keratinocyte cells and CHO-K1 mutant cell lines were irradiated using cobalt 60. Clonogenic assays were used to determine the reproductive death of the cells exposed to direct irradiation or medium from irradiated cells. The persistence in progeny was also examined. Use of apoptosis inhibitors or medium from the LDH or G6PD null cell lines, reduced or prevented the bystander effect. Transfection with G6PD recovered the effect. Treatment with anti-oxidant substances, L-lactate and L-deprenyl prevented bystander factor associated cell kill. The lactate analogue, oxamate, was less effective. Data from experiments where media harvested from the different cell lines was exchanged suggest that signal production and cellular response may involve different mechanisms. The effects on exposed cells were transmitted to progeny which also showed excessive levels of cell death for several generations. The results suggest that energy/REDOX metabolism may be involved in the expression of a radiation induced bystander response. Given the aberrant energy metabolism in tumour cells, this may have implications for dose escalation in radiotherapy.

2025, International Journal of Radiation Biology

2025, Radiation and Environmental Biophysics

2025, Environmental Science & Technology

2025, Results in Immunology

Cytokines play a key role in maintaining communication between organs and in so doing modulate the interaction between concurrent infections. The extent of these effects depends on the properties of the organ infected and the intensity and type of infections. To determine systemic bystander effects among organs, IFN-g, IL-4 and IL-10 gene expression was quantified at 7 days post-challenge in directly infected and uninfected organs during single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminths Graphidium strigosum and Trichostrongylus retortaeformis. Results showed that cytokine expression in a specific organ was influenced by the type of infection occurring in another organ, and this bystander effect was more apparent in some organs than others. Within the same organ the relative cytokine expression was consistent across infections, although some cytokines were more affected by bystander effects than others. For the infected gastrointestinal tract, a stronger cytokine response was observed in the tissue that harbored the majority of helminths (i.e. duodenum and fundus). Overall, co-infections altered the intensity but to a lesser extent the relative cytokine profile against the focal infection, indicating clear bystander effects and low organ compartmentalization. However, organs appear to actively modulate cytokine expression to avoid potential immuno-pathological consequences.

2025, Journal of School Violence

Bystander intervention has been an effective strategy for crime prevention and has been successful in the context of campus sexual assault. Less is known about the extent to which individual-level factors correlate with intervention behavior in situations of intimate partner violence and sexual harassment. The present study used a sample of 377 undergraduate student surveys on a campus without a bystander intervention program to examine the impact of individual-level participant factors on direct intervention across sexual assault, intimate partner violence and sexual harassment scenarios. Findings demonstrated statistically significant 1 differences where positive bystander attitudes and violence prevention efficacy correlated with direct intervention for sexual assault; positive bystander attitudes, personality extroversion and exposure to a victim increased intervention behavior in an IPV scenario, and positive bystander attitudes, violence prevention efficacy increased direct intervention and lifetime experience of IPV decreased direct intervention in a sexual harassment scenario. Research and policy implications are discussed.

2025, PubMed

An emerging strategy for cancer gene therapy involves the transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene into tumor cells, rendering them susceptible to the cytotoxic effects of ganciclovir. The observation that HSV-tk-expressing cells can also induce cell death in neighboring cells, which do not express HSV-tk, has been called the bystander effect. Gap junction-mediated transfer of cytotoxic molecules to bystander cells may be an important mechanism of bystander cell death, although others have suggested a role for phagocytosis. In this study, we evaluated the mode of cell death in bystander cells. We detected apoptosis in bystander cells and found that bystander cell death could be inhibited by BCL2 expression. We determined that ganciclovir incubations for 10 h were sufficient to induce cell death in most bystander cells cocultured with HSV-tk-expressing cells. During this period, no phagocytosis was detected, although it was obvious at later stages.

2025, Journal of Biomedical Physics and Engineering

Bystander or non-targeted effect is known to be an interesting phenomenon in radiobiology. The genetic consequences of bystander effect on non-irradiated cells have shown that this phenomenon can be considered as one of the most important factors involved in secondary cancer after exposure to ionizing radiation. Every year, millions of people around the world undergo radiotherapy in order to cure different types of cancers. The most crucial aim of radiotherapy is to improve treatment efficiency by reducing early and late effects of exposure to clinical doses of radiation. Secondary cancer induction resulted from exposure to high doses of radiation during treatment can reduce the effectiveness of this modality for cancer treatment. The perception of carcinogenesis risk of bystander effects and factors involved in this phenomenon might help reduce secondary cancer incidence years after radiotherapy. Different modalities such as radiation LET, dose and dose rate, fractionation, types o...

2025, Current radiopharmaceuticals

Knowledge of radiobiology is of paramount importance to be able to grasp and have an in-depth understanding of the consequences of ionizing radiation. One of the most important effects of this physical stressor's interaction to targeted and non-targeted cells, tissues and organs is on the late effects on the development of primary and secondary cancers. Thus, an in-depth understanding of the mechanisms of radiation carcinogenesis remain to be elucidated, and some studies have demonstrated or proposed a role of non-targeted effect in excess risk of cancer incidence. The non-targeted effect in radiobiology refers to a dynamic complex response in non-irradiated tissues caused by the release of presumably of clastogenic factors from irradiated cells. Although, most of these responses in non-targeted tissues have marked similarities to irradiated tissues, other studies have shown some differences. Also, the non-targeted effect has shown sex and tissue specificity that are seen in irr...

2025, Current molecular pharmacology

Each year, millions of people die from cancer. Radiotherapy is one of the main treatment strategies for cancer patients. Despite the beneficial roles of treatment with radiation, several side effects may threaten normal tissues of patients in the years after treatment. Moreover, high incidences of second primary cancers may reduce therapeutic ratio of radiotherapy. The search for appropriate targets of radiosensitization of tumor cells as well as radioprotection of normal tissues is one of the most interesting aims in radiobiology. Cyclooxygenase-2 (COX-2), as an inflammatory mediator has attracted interests for both aims. COX-2 activity is associated with ROS production and inflammatory signs in normal tissues. These effects further amplify radiation toxicity in irradiated cells as well as adjacent cells through a phenomenon known as Bystander effect. Increased COX-2 expression in distant non-irradiated tissues causes oxidative DNA damage and elevated cancer risk. Moreover, in tumo...

2025, Journal of Experimental Social Psychology

The current article addresses bystander action to confront disparaging humor as a form of moral courage. We ask: When is disparaging humor seen as harmless fun or as a pernicious form of prejudice? What are the social and psychological processes through which bystanders confront, evade, or collaborate in disparaging humor? Three experiments (Ns = 95, 213, 220), involving a novel paradigm ('the shared media paradigm') test the role of bystander emotional responses (anger/amusement) in shaping action to confront disparagement humor, through emotion-based social influence. Study 1 demonstrates that bystander action to confront disparagement humor as prejudice is shaped by the angry (but not amused) responses of co-present others. Study 2 considers a moderator of the influence process: the role of one's own emotional reaction to disparagement humor (angry/ amused). Bystander confrontation was more intense when one's own angry reaction was validated by that of other bystanders but there was otherwise mixed evidence that the two interacted to promote collaboration/ confrontation. Study 3 tests the claim that disparagement humor is especially challenging to confront because humor disarms opposition. Intergroup commentary was seen as more amusing and confrontation was more strongly resisted when humor was used (vs. a non-humorous control remark). Overall, the results show that the reactions of bystanders play an important role in shaping what is (or is not) perceived to be prejudice. Courageous action to confront the disparagement of members of minority groups is enabled by the emotional signals of others who are co-present. humor is typically seen as a more 'acceptable' form of intergroup commentary because the levity with which the remark is delivered suggests that it should not be taken seriouslyafter all, it is "just a joke" . However, disparaging humor, even where it trades on ostensibly benign stereotypes, is deeply problematic (see Ferguson & Ford, 2008 for reviews). Such humor reinforces intolerant attitudes and derogatory stereotypes (e.g., and shifts the normative context to one that supports discrimination (Ford et al.

2025, Radiation Physics and Chemistry

Radiations in medicine cover a wide range of applications, predominantly in diagnostic imaging and radiotherapy, encompassing photons (x-and γ-rays) and particle radiation, as well as with the use of liquid sources in nuclear medicine focusing on physiological functional imaging, tumour detection or targeted radiotherapy. The biological interactions of ionizing radiation leads naturally to questions of benefits and risk following dose exposures. The inherent properties of ionizing radiation in sterilising dividing cells can offer immense benefits with respect to tumour control, but radiation can also deliver potential harm in the form of normal tissue toxicity or carcinogenesis. The advances in radiation technology, offering accurate and reliable dose delivery, in concert with greater understanding of the underpinning radiobiological effects are creating an ever-growing ability to extract maximum benefit and minimise risk. The radiobiological effects fall broadly under the headings of mutagenesis, chromosomal aberrations, radiation induced genomic instability and cell death. The enormity of evidence derived from these underlie the mechanism of the six Rs of controlled radiotherapy: repair, repopulation, reoxygenation, redistribution, radiosensitivity and most recently, remote bystander cellular effects (including low dose hyper-radiosensitivity, adaptive response, hormesis, abscopal effect and immune response). Herein, we seek to discuss how such understanding leads to optimised radiotherapy.

2025, British Journal of Haematology

2025, Resuscitation

Understanding regional variation in bystander cardiopulmonary resuscitation (CPR) is important to improving out-of-hospital cardiac arrest (OHCA) survival. In this study we aimed to identify barriers to providing bystander CPR in regions with low rates of bystander CPR and where OHCA was recognised in the emergency call. We retrospectively reviewed emergency calls for adults in regions of low bystander CPR in the Australian state of Victoria. Included calls were those where OHCA was identified during the call but no bystander CPR was given. A thematic content analysis was independently conducted by two investigators. Saturation of themes was reached after listening to 139 calls. Calls progressed to the point of compression instructions before EMS arrival in only 26 (18.7%) of cases. Three types of barriers were identified: procedural barriers (time lost due to language barriers and communication issues; telephone problems), CPR knowledge (skill deficits; perceived benefit) and perso...

2025, Journal of Pharmacokinetics and Pharmacodynamics

Antibody-drug conjugates (ADCs) are designed to target antigen expressing (Ag+) cells in a tumor. Once processed by the Ag+ cells, ADCs can release cytotoxic drug molecules that can diffuse out of Ag+ cells into the neighboring antigen-negative (Ag-) cells to induce their cytotoxicity. This additional efficacy of ADCs on Ag-cells in the presence of Ag+ cells is known as the `bystander effect'. Although the importance of this phenomena is widely acknowledged for effective killing of a heterogeneous tumor, the rate and extent of the bystander killing in a heterogeneous system is not quantitatively understood yet. Thus, the objectives of this manuscript were to: 1) synthesize and characterize a tool ADC Trastuzumab-vc-MMAE that is capable of exhibiting bystander effect, 2) quantify the time course of the bystander effect for the tool ADC using in vitro co-culture systems created using mixture of various HER2-expressing cell lines, and 3) develop a pharmacodynamic (PD) model that is capable of characterizing the bystander effect of ADCs. Co-culture studies conducted using GFP labelled MCF7 cells as Ag-cells and N87, BT474, and SKBR3 as Ag+ cells revealed that the bystander effect of ADC increases with increasing fraction of Ag+ cells in a co-culture system, and with increased expression level of target on Ag+ cells. A notable lag time after ADC incubation was also observed prior to significant bystander killing of Ag-cells. Based on our results we hypothesize that there may be other determinants apart from the antigen expression level that can also influence the ability of Ag + cells to demonstrate the bystander effect in a co-culture system. The co-culture analysis also suggested that the bystander effect of the ADC can dissipate over the period of time as the population of Ag+ cells declines. A novel PD model was developed to mathematically characterize the bystander effect of ADCs by combining two different cell distribution models to represent the population of Ag+ and Ag-cells in a co-culture system. This PD model can be integrated with the systems PK model for ADCs in the future to generate a quantitative framework that is capable of supporting the discovery and development of novel ADCs with optimal bystander killing capabilities.

2025, Cancers

Ionizing radiation-induced bystander effects (RIBE) encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR), something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization, and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO) related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological ...

2025, Jurnal AKSI (Akuntansi dan Sistem Informasi)

This study aims to determine the effect of personal cost on whistleblowing intention with the bystander effect as a moderating variable. The population in this study were students of the Faculty of Economics and Business, W University who are active in organization. The data analysis technique used is moderated regression analysis. The result of this study indicate that personal cost has a negative effect on whistleblowing intention and bystander effect has a negative effect which strengthens the negative effect of personal cost on whistleblowing intention.

2025, PLOS ONE

One third of the human population is currently infected by one or more species of parasitic helminths. Certain helminths establish long-term chronic infections resulting in a modulation of the host's immune system with attenuated responsiveness to ''bystander'' antigens such as allergens or vaccines. In this study we investigated whether parasitederived products suppress the development of allergic inflammation in a mouse model. We show that extract derived from adult male Oesophagostomum dentatum (eMOD) induced Th2 and regulatory responses in BALB/c mice. Stimulation of bone marrow-derived dendritic cells induced production of regulatory cytokines IL-10 and TGF-beta. In a mouse model of birch pollen allergy, co-administration of eMOD with sensitizing allergen Bet v 1 markedly reduced the production of allergenspecific antibodies in serum as well as IgE-dependent basophil degranulation. Furthermore, eMOD prevented the development of airway inflammation, as demonstrated by attenuation of bronchoalveolar lavages eosinophil influx, peribronchial inflammatory infiltrate, and mucus secretion in lungs and IL-4 and IL-5 levels in lung cell cultures. Reduced secretion of Th2-related cytokines by birch pollen-re-stimulated splenocytes and mesenteric lymph node cells was observed in eMOD-treated/sensitized and challenged mice in comparison to sensitized and challenged controls. The suppressive effects of eMOD were heat-stable. Immunization with model antigens in the presence of eMOD reduced production of antibodies to thymus-dependent but not to thymus-independent antigen, suggesting that suppression of the immune responses by eMOD was mediated by interference with antigen presenting cell or T helper cell function but did not directly suppress B cell function. In conclusion, we have shown that eMOD possesses immunomodulatory properties and that heatstable factors in eMOD are responsible for the dramatic suppression of allergic responses in a mouse model of type I allergy. The identification and characterization of parasite-derived immune-modulating molecules might have potential for designing novel prophylactic/therapeutic strategies for immune-mediated diseases.

2025, PLoS ONE

2025, Frontiers in Public Health

Life has evolved on Earth for about 4 billion years in the presence of the natural background of ionizing radiation. It is extremely likely that it contributed, and still contributes, to shaping present form of life. Today the natural background radiation is extremely small (few mSv/y), however it may be significant enough for living organisms to respond to it, perhaps keeping memory of this exposure. A better understanding of this response is relevant not only for improving our knowledge on life evolution, but also for assessing the robustness of the present radiation protection system at low doses, such as those typically encountered in everyday life. Given the large uncertainties in epidemiological data below 100 mSv, quantitative evaluation of these health risk is currently obtained with the aid of radiobiological models. These predict a health detriment, caused by radiation-induced genetic mutations, linearly related to the dose. However a number of studies challenged this para...

2025, Il Nuovo Cimento C

Charged particle effects: Experimental and theoretical studies on the mechanisms underlying the induction of molecular and cellular damage and the modulation of intercellular signalling ), E. Sorrentino( 3 )( 4 ), M. A. Tabocchini( 3 )( 4... more

2025, Radiation Research

An experimental system based on an improved version of an existing a-particle irradiator has been developed for radiobiological studies, in particular those investigating bystander effects. It consists of a 20-mm-diameter stainless steel chamber that can be equipped alternatively with 244 Cm or 241 Am sources of different activities. MylarH-based petri dishes 56 mm in diameter were specially designed to house adaptors for permeable membrane inserts that reproduce the geometry of commercial cell culture insert companion plates. Characterization of the radiation field at the cell level was performed by experimental measurements and calculations. The average incident LET was about 122 keV/mm for 244 Cm and about 125 keV/mm for 241 Am. Dose rates at the chosen source-sample distance were 2.8 and 88.6 mGy/min, respectively. These low dose rates are suitable for our planned experiments on low-dose effects. For both sources, the uniformity of the a-particle dose was better than ±7%, and the photon dose calculated at the cell entrance was negligible compared to the a-particle dose. The irradiator is small enough to be inserted into a cell incubator for irradiation under physiological conditions or into a refrigerator to prevent metabolic processes during irradiation. Benchmark experiments using the 241 Am source to examine DNA doublestrand breaks in directly hit and bystander primary human fibroblasts have shown that the irradiator can be used successfully for bystander effect studies.

2025, Cancer immunology research

The development of targeted therapies that affect multiple signaling pathways and stimulate antitumor immunity is greatly needed. About 20% of patients with breast cancer overexpress HER2. Small molecules and antibodies targeting HER2 convey some survival benefits, however patients with advanced disease succumb to the disease under these treatment regimens, possibly because HER2 is not completely necessary for the survival of the targeted cancer cells. In the present study we show that a polyinosine/polycytosine (pIC) HER2-homing chemical vector induced the demise of HER2-overexpressing breast cancer cells, including trastuzumab-resistant cells. Targeting pIC to the tumor evoked a number of cell-killing mechanisms, as well as strong bystander effects. These bystander mechanisms included type I IFN induction, immune cell recruitment, and activation. The HER2-targeted pIC strongly inhibited the growth of HER2-overexpressing tumors in immune competent mice. The data presented here coul...

2025, Revista INFAD de Psicología. International Journal of Developmental and Educational Psychology.

La alta prevalencia de la violencia en el noviazgo (VN) entre los adolescentes y las consecuencias que puede tener para los individuos ponen de manifiesto la necesidad de estudiar sobre este fenómeno. Existen, de momento, pocos estudios que traten la violencia en el noviazgo con la intervención de los espectadores. En el presente trabajo se pretende examinar algunos de los factores que pueden influir en la intervención o no del espectador ante una situación de VN. Para ello, se administró un cuestionario a 64 adolescentes de entre 14 y 19 años. Los resultados mostraron que las mujeres habían estado más expuestas a la violencia que los hombres y que estos últimos la justifican más. Asimismo, tanto la nula como la alta frecuencia a la exposición de violencia en el noviazgo (más de 4 veces) predecía una alta tolerancia y justificación de la violencia. Sin embargo, la baja frecuenciade exposición a la violencia (entre 1-3 veces) marcaba una reducción de la tolerancia y justificación de ...

2025, Biology

Ionizing Radiation (IR), especially at high doses, induces cellular senescence in exposed cultures. IR also induces “bystander effects” through signals released from irradiated cells, and these effects include many of the same outcomes observed following direct exposure. Here, we investigate if radiation can cause senescence through a bystander mechanism. Control cultures were exposed directly to 0, 0.1, 2, and 10 Gy. Unirradiated cells were treated with medium from irradiated cultures or with exosomes extracted from irradiated medium. The level of senescence was determined post-treatment (24 h, 15 days, 30 days, and 45 days) by β-galactosidase staining. Media from cultures exposed to all four doses, and exosomes from these cultures, induced significant senescence in recipient cultures. Senescence levels were initially low at the earliest timepoint, and peaked at 15 days, and then decreased with further passaging. These results demonstrate that senescence is inducible through a byst...

2025, Il Nuovo Cimento C

2025

CD4 � CD25 � regulatory T cells (T Reg) play a critical role in the control of autoimmunity. However, little is known about how T Reg suppress self-reactive T cells in vivo, thus limiting the development of T Reg-based therapy for treating autoimmune diseases. This is in large part due to the dependency on a state of lymphopenia to demonstrate T Reg-mediated suppression in vivo and the unknown Ag specificity of T Reg in most experimental models. Using a nonlymphopenic model of autoimmune pneumonitis and T Reg with known Ag specificity, in this study we demonstrated that these T Reg can actively suppress activation of self-reactive T cells and protect mice from fatal autoimmune pneumonitis. The protection required T Reg with the same Ag specificity as the self-reactive T cells and depended on IL-10 and TGF-�. These results suggest that suppression of autoimmunity by T Reg in vivo consists of multiple layers of regulation and advocate for a strategy involving Ag-specific T Reg for tre...

2025, Oncogene

Homologous recombination can induce tumorigenic sequence rearrangements. Here, we show that persistent hyper-recombination can be induced following exposure to a bifunctional alkylating agent, mitomycin C (MMC), and that the progeny of exposed cells induce a hyperrecombination phenotype in unexposed neighboring cells. Residual damage cannot be the cause of delayed recombination events, since recombination is observed after drug and template damage are diluted over a millionfold. Furthermore, not only do progeny of MMC-exposed cells induce recombination in unexposed cells (bystanders), but these bystanders can in turn induce recombination in their unexposed neighbors. Thus, a signal to induce homologous recombination can be passed from cell to cell. Although the underlying molecular mechanism is not yet known, these studies reveal that cells suffer consequences of damage long after exposure, and that can signal unexposed neighboring cells to respond similarly. Thus, a single acute exposure to a chemotherapeutic agent can cause long-term changes in genomic stability. If the results of these studies of mouse embryonic stem (ES) cells are generally applicable to many cell types, these results suggest that a relatively small number of cells could potentially induce a tissue-wide increase in the risk of de novo homologous recombination events.

2025, International Journal of Emotional Education

This study aimed to ascertain how the four domains of self-debasing cognitive distortion, namely personalisation, catastrophising, overgeneralisation and selective abstraction, could predict or inform emotional disturbance in the reactions of bystanders when witnessing bullying behaviour. We utilised purposive sampling to select 10 bystanders of school bullying for participation in the study and performed convenient sampling to select a research site. We conducted interviews that were recorded on a voice recorder and transcribed thereafter. Qualitative data was analysed through inductive thematic analysis. Our findings revealed that personalisation evoked bystanders' self-blame and feelings of guilt, catastrophising amplified their anxiety and fear, overgeneralisation induced and exacerbated their negative perception of school safety, and selective abstraction led to indirect co-victimisation. Based on our findings, we recommend that school psychologists, counsellors and behavioural healthcare service providers should teach victims of bullying, especially bystanders, how to recognise, challenge and reappraise negative and unhelpful thoughts and feelings related to their experiences.

2025

This paper addresses a critical ambiguity in the Non-Aggression Principle (NAP), a cornerstone of libertarian philosophy that prohibits initiating force against others. While effectively guiding two-party interactions, the NAP lacks clarity regarding third-party bystander intervention. Utilizing formal logic and set theory, this study identifies a logical 'NULL state' inherent in traditional NAP formulations, which leaves bystander actions undefined. To resolve this, the paper introduces a modified NAP (MNAP), explicitly permitting voluntary, consent-based bystander intervention. The proposed refinement enhances the practical applicability of the NAP in complex multi-agent scenarios, offering libertarian societies a coherent framework for ethically and legally addressing immediate situations of aggression through consensual collective action.

2025, Expert review of vaccines

The current status of therapeutic vaccines for autoimmune diseases is reviewed with rheumatoid arthritis as the focus. Therapeutic vaccines for autoimmune diseases must regulate or subdue responses to common self-antigens. Ideally, such a vaccine would initiate an antigen-specific modulation of the T-cell immune response that drives the inflammatory disease. Appropriate animal models and types of T helper cells and signature cytokine responses that drive autoimmune disease are also discussed. Interpretation of these animal models must be done cautiously because the means of initiation, autoantigens, and even the signature cytokine and T helper cell (Th1 or Th17) responses that are involved in the disease may differ significantly from those in humans. We describe ligand epitope antigen presentation system vaccine modulation of T-cell autoimmune responses as a strategy for the design of therapeutic vaccines for rheumatoid arthritis, which may also be effective in other autoimmune cond...