Dose-Response最新文献

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.

Objective: MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression and remain stable in biological fluids, even under harsh conditions. Their stability and responsiveness to environmental stressors make them strong candidates for radiation biodosimetry. This study aimed to (1) establish a robust in vivo pipeline for miRNAome profiling and (2) identify plasma-based miRNA biomarkers of ionizing radiation at low and high doses.

Methods: BALB/c mice were exposed to sham, 100 mGy, or 2 Gy of X-rays. Plasma was collected 6 h post-irradiation. Total RNA was extracted, and next-generation sequencing was used to profile the plasma miRNAome. Differentially expressed miRNAs were identified relative to sham controls, and selected candidates were validated using RT-qPCR.

Results: A total of 630 unique miRNAs were detected. High-dose exposure (2 Gy) significantly upregulated 14 and downregulated 5 miRNAs. Seven miRNAs were significantly induced at 100 mGy, including miR-126a-5p and miR-133a-3p, which were exclusive to low-dose exposure. Five miRNAs were shared between both doses, indicating dose-independent responses. RT-qPCR confirmed expression trends.

Conclusion: This study identified distinct and shared circulating miRNA signatures for low- and high-dose radiation exposure. These findings support the potential of miRNAs as minimally invasive, dose-stratified biomarkers for radiation biodosimetry.

Objective: High-throughput gene expression analysis represents a promising approach for evaluating irradiation doses in vitro. This study aimed to identify preferred reference genes for normalizing RT-qPCR data in human peripheral blood following X-ray irradiation.

Methods: We assessed the stability of GAPDH, 18S rRNA, UBC, HPRT, DPM1, ITFG1, MRPS5, and ACTB, which are commonly utilized in radiation biodosimetry studies. Three whole blood samples from healthy donors were divided into three culture time groups (2, 12, and 24 hours) and subjected to X-ray doses of 0, 0.5, 1.2, and 3.5 Gy, resulting in a total of 12 subgroups. NormFinder, geNorm, BestKeeper, and ΔCt were employed to evaluate the stability of the candidate genes. RefFinder was utilized to comprehensively rank the candidates and identify suitable reference genes.

Results: The preferred reference genes identified were UBC, HPRT, and GAPDH for 2-hour culture time; for 12 hours, UBC, HPRT, and 18S rRNA were preferred; and for 24 hours, 18S rRNA, MRPS5, and GAPDH were preferred.

Conclusion: This study presents novel findings of reference genes suitable for normalizing RT-qPCR data following X-ray irradiation in human peripheral blood across three distinct culture periods. It offers valuable insights for the selection of reference genes in radiation biodosimetry research.

This mini-review explores adaptive responses in organisms exposed to high radiation levels, drawing comparisons between Chernobyl's wildlife-specifically its darker-pigmented frogs-and residents of Ramsar, Iran, a region with high natural background radiation. Chernobyl's wildlife adaptations are not surprising, as substantial evidence in humans, demonstrates similar adaptation to high radiation levels. Studies reveal that mechanisms such as increased melanin production in frogs and enhanced DNA repair capabilities in Ramsar residents help mitigate radiation damage. These adaptations provide a framework for understanding resilience to environmental stressors and contribute to broader discussions on evolutionary survival mechanisms in extreme environments. By examining ecological and physiological responses across species, this review sheds light on radiation's role in natural selection and potential applications for environmental and radiobiological research.

Background: Radiation therapy for brain tumors often leads to radiation-induced brain injury, which is closely linked to microglial hyperactivation and neuroinflammation. Lycium barbarum polysaccharide (LBP), the primary active component of Lycium barbarum, may provide neuroprotection by suppressing microglial overactivation and reducing neuroinflammation.

Methods: BV2 microglial cells were pretreated with LBP for 12 hours (h), exposed to 10 Gy X-ray irradiation, and then post-treated with LBP for another 12 h. We assessed microglial polarization and measured levels of nitric oxide (NO), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and key proteins in the IKKβ/IκBα/NF-κB pathway.

Results: LBP treatment shifted microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype and significantly decreased the release of NO, IL-1β, and TNF-α following irradiation.

Conclusion: Our findings demonstrate that LBP mitigates radiation-induced microglial inflammation by inhibiting the IKKβ/IκBα/NF-κB pathway, suggesting its potential as a radioprotective agent against radiotherapy-induced neuroinflammation.

Traumatic brain injury (TBI) is an important condition with high rates of disability and mortality worldwide. Post-traumatic seizure (PTS) frequently occur following TBI, manifesting in both early and late stages. Recurrent PTS without timely intervention may progress to post-traumatic epilepsy (PTE), which defined as the occurrence of two or more unprovoked seizures. Early pharmacological intervention is essential to mitigate the risk of PTE and enhance the prognosis for patients with TBI. Antiepileptic drugs (AEDs) offer a viable strategy for managing PTS. Recent studies indicated that AEDs are more effective in early post-traumatic seizure compared to late post-traumatic seizure, and their efficacy and safety require further evaluation. As research advances in the pathophysiological changes after TBI and the pathogenesis of PTS, current investigations are increasingly focused on neurological damage. Novel compounds targeting various pathways, including antioxidants, anti-neuroinflammatory agents, glutamate modulators and anti-oxidative stress compounds, have demonstrated promising potential in preclinical studies for PTS intervention. This review focuses on the research progress of different AEDs in PTS intervention and discusses the recent developments of emerging PTS intervention strategies based on multiple pathways, providing insights into the clinical application of AEDs and new directions for the development of new drugs for PTS intervention.

Risk estimates for solid cancer mortality are much higher in the INWORKS study than in the LSS study.^1,2 However, some analysts have reached the opposite conclusion by comparing non-equivalent risk estimates in the 2 studies.³.

[This retracts the article DOI: 10.1177/1559325819891262.].

Background: In the present study, the therapeutic effects of Toosendanin (TSN) against Mycoplasma pneumoniae (MP)-induced pneumonia (MPP) in mice.

Research design: Swiss albino mice were exposed to MP culture for 2 days, causing pneumonia, and then treated with TSN for 3 days. Lung weights, total protein, IgM, C-reactive protein, oxidative stress, and inflammatory cytokines were assessed. Histological alterations were evaluated in lung tissues. Molecular docking analysis was performed to test TSN's interaction with inflammatory cytokines, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), transforming growth factor-beta 1 (TGF-β1), and nuclear factor kappa B (NF-κB) were evaluated targets.

Results: TSN treatment significantly reduced lung weight by approximately 25% compared to the MP-infected group (P < 0.05). Total protein and C-reactive protein (CRP) levels decreased by 30% and 40%, respectively. Malondialdehyde (MDA), was reduced by 35%, while antioxidant enzyme levels (e.g., SOD, CAT) increased by 20%-25%. Pro-inflammatory cytokines such as IL-1β and IL-6 were significantly lowered by 40%-50%. Histological analysis revealed a marked reduction in inflammatory cell infiltration and alveolar damage scores (P < 0.01). Molecular docking confirmed strong binding interactions between IL-1β, IL-6, TGF-β1, NF-κB and TSN.

Conclusions: The present findings confirm the beneficial effects of TSN in protecting mice from pneumonia.

FLASH radiotherapy (FLASH-RT) is a radiotherapy technique that achieves ultra-high dose rates in a fraction of a second. Based on data from experimental animal models, FLASH-RT appears to protect a number of normal tissues from radiation-induced damage, including the brain, gastrointestinal tract, and lung, while conventional radiotherapy (CONV-RT) causes radiation-induced toxicity in these tissues. In this review, we provide a brief summary of the history of radiation therapy and focus on some of the most recent FLASH-RT papers and findings. It is particularly noteworthy that pulmonary fibrosis represents a common complication of radiotherapy. New evidence indicates that FLASH-RT, unlike traditional radiotherapy methods, might help protect lung cancer patients from developing pulmonary fibrosis caused by radiation. FLASH-RT will advance more quickly than anticipated, although there are still a number of unresolved concerns. FLASH-RT will be a safer and more effective option for lung cancer treatment.