Advancing Dose-Response Research: Integrating Exposome,Multi-Omics,and Low-Dose Phenomena in Toxicology and Medicine

Abstract

The field of dose-response research has evolved dramatically, propelled by advancements in exposomics concept, multi-omics technologies, and a growing appreciation of low-dose effects across disciplines. This editorial article highlights recent key publications in Dose-Response that reflect these trends and outlines the journal’s renewed commitment to publishing rigorous, innovative research that bridges traditional toxicology with modern systems biology. Meanwhile, this editorial article also addresses the future directions for Dose-Response. Finally, Dose-Response will remain dedicated to advancing the science of biological responsiveness to low-dose stressors. By embracing exposomics, multi-omics, and mechanistic toxicology, we aim to foster interdisciplinary dialogue and translate research into evidence-based policies. Through collaboration with our authors, reviewers, and readers, from global scientific community, we wish and also confident to reach this exciting new chapter.

Introduction

The field of dose-response research has evolved dramatically, propelled by advancements in exposomics concept, multi-omics technologies, and a growing appreciation of low-dose effects across disciplines. This editorial article highlights recent key publications in Dose-Response that reflect these trends and outlines the journal’s renewed commitment to publishing rigorous, innovative research that bridges traditional toxicology with modern systems biology.

The Expanding Scope of Dose-Response Research

Dose-response relationships are fundamental to toxicology, pharmacology, and environmental health. Historically, the linear no-threshold (LNT) model dominated risk assessment, but emerging evidence supports nonlinear, hormetic, or threshold responses at low doses. Recent studies published in Dose-Response exemplify this shift, emphasizing the need to integrate holistic exposure assessment (exposome) and molecular profiling (-omics) to capture complex biological responses.

Low-Dose Radiation, Hormetic or Adaptive Responses

Janiak and Waligorski ¹ critically evaluated the LNT model, arguing that low-dose ionizing radiation often induces a stimulating effect, called either hormetic or adaptive effect (eg, radioprotection), challenging conventional risk paradigms since low-dose radiation is able to stimulate the body’s defense system such as antioxidant capacity. Scott ² further proposed replacing LNT with threshold-based models, citing evidence from A-bomb survivors and animal studies where low-dose radiation reduced cancer risk.

Hormesis induced by low-dose radiation often shows the resistance to subsequent radiation-induced or pathogenic challenges, which was called adaptive response ³ and attributed to the stimulation of the body’s defense and antioxidant capacity. To support the protective effects of pre-induction of antioxidants activity by low-dose radiation, Shedid et al recent publication in this journal demonstrated that exogenous administration of melatonin mitigates radiation-induced ovarian damage through antioxidant and anti-inflammatory mechanisms. ⁴ Shibrya et al ⁵ further showed that low-dose gamma radiation and apigenin ameliorated acetic acid-induced ulcerative colitis in rats by modulating oxidative stress and inflammatory markers, confirming the cross-adaptive response induced by low-dose radiation to subsequent chemics-induced pathogenesis. Zhao et al ⁶ found that low-dose radiation preconditioning attenuated doxorubicin-induced cardiotoxicity by improving mitochondrial function, also illustrating cross-adaptation mechanisms. Notably, Gharib et al ⁷ determined the efficacy of mesenchymal stem cells and low-dose gamma radiation on liver injury compared to the effect of olive leaf extract as a hepatoprotective agent, and found that low-dose gamma radiation provided protective mechanisms that allow the body to survive better. Therefore, these studies have highlighted the therapeutic potential of low-dose exposures.

Natural Compounds and Dose-Dependent Bioactivities

Multiple studies explored the therapeutic potential of phytochemicals. For instance, Rana et al ⁸ reported dose-dependent amelioration of polycystic ovarian syndrome using Garcinia cambogia extract, linked to antioxidant and hormonal modulation. Xi et al ⁹ showed that curcumin inhibits gastric cancer progression via PI3K pathway blockade in a dose-dependent manner. These findings highlight the importance of quantifying dose-effects for natural products in disease management. Additionally, Tehami et al ¹⁰ provided insights into the anticancer effects of p-coumaric acid on colorectal cancer, emphasizing its dose-dependent anti-inflammatory and pro-apoptotic properties. Mohsin et al ¹¹ reviewed the dose-responsive effects of cinnamon derivatives on insulin resistance in type II diabetes, showcasing the nutraceutical potential of natural compounds. Similarly, Ekpono et al ¹² demonstrated the dose-dependent ameliorative effects of pumpkin seed oil against tramadol-induced oxidative stress in rats, reinforcing the role of natural antioxidants in adaptive responses. Sammari et al ¹³ showed that berries decoction extract protected against acetic acid-induced ulcerative colitis in a dose-dependent manner. Ishak et al ¹⁴ detected the antiproliferative activities and cytotoxicity effects of acetone extract from C. odontophyllum stem bark against human colorectal cancer cell lines. Rana et al ¹⁵ explored the therapeutic potential of Garcinia cambogia against letrozole induced polycystic ovarian syndrome.

Environmental Exposures and Mechanistic Insights

Palacio et al ¹⁶ reviewed experimental evidence on air pollution-induced cardiac damage, emphasizing non-linear dose-effects for pollutants like PM2.5 and NO₂. Alothaid et al ¹⁷ used transcriptomics to reveal gene expression changes in hepatocellular carcinoma cells exposed to cadmium telluride quantum dots, linking low-dose exposure to altered stress response pathways. Furthermore, Fouad et al ¹⁸ demonstrated the insecticidal and repellent activities of essential oils against Sitophilus zeamais in a dose-dependent manner, providing an eco-friendly alternative to chemical pesticides. Hassan et al ¹⁹ evaluated the antioxidant properties of traditional medicinal plants against lipid peroxidation, revealing dose-dependent inhibitory effects on oxidative stress in mice brain and liver.

Novel Methodologies and Risk Assessment

Advanced technique in the medical practice definitely brought us benefits, but sometime may also bring us certain hindered heathy risks. For instance, CT scan has been extensively used in clinics; however, Dellie et al established local diagnostic reference levels for CT scans in Ethiopia, addressing geographic variability in radiation exposure. ²⁰

Abbas and Trari ²¹ optimized adsorption parameters for amoxicillin removal from wastewater using response surface methodology, demonstrating how dose-response modeling can enhance environmental remediation. These authros also explored the adsorption behavior of methylene blue onto activated coconut shells, highlighting dose-dependent kinetic and thermodynamic processes. ²² Additionally, Bukhari et al ²³ developed poly lactic-co-glycolic acid nano-carriers for controlled release of ciprofloxacin, demonstrating dose-dependent enhancements in bioavailability and antimicrobial properties.

Dose-Response in Pharmacology and Therapeutics

Ma et al ²⁴ compared the anesthetic and analgesic effects of esketamine and racemic ketamine in mice, revealing dose-dependent potency differences. Xiong et al ²⁵ determined the median effective dose of ciprofol combined with sufentanil for inhibiting upper gastrointestinal endoscopic placement reactions in elderly patients, emphasizing the importance of dose optimization in clinical settings. Ogata et al ²⁶ investigated the dose-dependent effect of sulfamethoxazole on KATP channels in pancreatic β-cells, providing mechanistic insights into drug-induced hypoglycemia. Han et al ²⁷ conducted a dose-dependent study on the anxiolytic and antidepressant effects of Neurada procumbens extract in mice, highlighting its potential in neurodegenerative disorders.

Integrating Exposome and Multi-Omics in Dose-Response

The concept of the exposome—encompassing lifelong environmental exposures—has transformed toxicology. Coupled with omics technologies (genomics, proteomics, metabolomics), it enables unprecedented resolution in linking exposures to health outcomes. For example, Zhang et al ²⁸ identified X-ray-specific gene signatures in mouse lungs post-irradiation, providing biomarkers for latent radiation injury. Chen et al ²⁹ used polydatin to suppress radon-induced oxidative stress and epithelial-mesenchymal transition via PI3K/AKT/mTOR inhibition, showcasing multi-mechanistic dose-response analyses. Liu et al ³⁰ explored the role of endoplasmic reticulum stress in predicting cervical cancer prognosis and regulating radiation mucositis, integrating genomic and clinical data. Zhang et al ³¹ also revealed a biphasic dose-response of manganese-induced mitochondrial damage and mitophagy in neuroblastoma cells, emphasizing the complex interplay between dose and cellular adaptive mechanisms.

Future Directions for Dose-Response

Building on these advances, Dose-Response will prioritize studies that.

• Apply exposomic frameworks to chronic disease etiology.

• Utilize multi-omics to decipher nonlinear dose-response mechanisms.

• Explore low-dose hormesis in environmental, pharmacological, and radiation contexts.

• Develop computational models integrating real-world exposure data with biological responses.

• Address ethical and societal implications of low-dose exposures, such as environmental justice and regulatory policies.

Conclusion

Dose-Response remains dedicated to advancing the science of biological responsiveness to low-dose stressors. By embracing exposomics, multi-omics, and mechanistic toxicology, we aim to foster interdisciplinary dialogue and translate research into evidence-based policies. ³² We thank our authors, reviewers, and readers for their contributions and invite the global scientific community to join us in this exciting new chapter.