Background: The placenta exerts a crucial role in fetus growth and development during gestation, protecting the fetus from maternal drugs and chemical exposure. However, diverse drugs and chemicals (xenobiotics) can penetrate the maternal placental barrier, leading to deleterious, adverse effects concerning fetus health. Moreover, placental enzymes can metabolize drugs and chemicals into more toxic compounds for the fetus. Thus, evaluating the molecular mechanisms through which drugs and chemicals transfer and undergo metabolism across the placental barrier is of vital importance. In this aspect, this comprehensive literature review aims to provide a holistic approach by critically summarizing and scrutinizing the potential molecular processes and mechanisms governing drugs and chemical transfer and metabolism across the placental barrier, which may lead to fetotoxicity effects, as well as analyzing the currently available experimental methodologies used to assess xenobiotics placental transfer and metabolism. Methods: A comprehensive and in-depth literature review was conducted in the most accurate scientific databases such as PubMed, Scopus, and Web of Science by using relevant and effective keywords related to xenobiotic placental transfer and metabolism, retrieving 8830 published articles until 5 February 2024. After applying several strict exclusion and inclusion criteria, a final number of 148 relevant published articles were included. Results: During pregnancy, several drugs and chemicals can be transferred from the mother to the fetus across the placental barrier by either passive diffusion or through placental transporters, resulting in fetus exposure and potential fetotoxicity effects. Some drugs and chemicals also appear to be metabolized across the placental barrier, leading to more toxic products for both the mother and the fetus. At present, there is increasing research development of diverse experimental methodologies to determine the potential molecular processes and mechanisms of drug and chemical placental transfer and metabolism. All the currently available methodologies have specific strengths and limitations, highlighting the strong demand to utilize an efficient combination of them to obtain reliable evidence concerning drug and chemical transfer and metabolism across the placental barrier. To derive the most consistent and safe evidence, in vitro studies, ex vivo perfusion methods, and in vivo animal and human studies can be applied together with the final aim to minimize potential fetotoxicity effects. Conclusions: Research is being increasingly carried out to obtain an accurate and safe evaluation of drug and chemical transport and metabolism across the placental barrier, applying a combination of advanced techniques to avoid potential fetotoxic effects. The improvement of the currently available techniques and the development of novel experimental protocols and methodologies are of major importance to protect both the mother and the fetus from xenobiotic exposure, as well as to minimize potential fetotoxicity effects.

Hu-antigen R (HuR) is an RNA-binding posttranscriptional regulator that belongs to the Hu/ELAV family. HuR expression levels are modulated by a variety of proteins, microRNAs, chemical compounds, or the microenvironment, and in turn, HuR affects mRNA stability and translation of various genes implicated in breast cancer formation, progression, metastasis, and treatment. The aim of the present review is to critically summarize the role of HuR in breast cancer development and its potential as a prognosticator and a therapeutic target. In this aspect, all the existing English literature concerning HuR expression and function in breast cancer cell lines, in vivo animal models, and clinical studies is critically presented and summarized. HuR modulates many genes implicated in biological processes crucial for breast cancer formation, growth, and metastasis, whereas the link between HuR and these processes has been demonstrated directly in vitro and in vivo. Additionally, clinical studies reveal that HuR is associated with more aggressive forms of breast cancer and is a putative prognosticator for patients' survival. All the above indicate HuR as a promising drug target for cancer therapy; nevertheless, additional studies are required to fully understand its potential and determine against which types of breast cancer and at which stage of the disease a therapeutic agent targeting HuR would be more effective.

The ozone layer in the Earth’s atmosphere filters solar radiation and limits the unwanted effects on humans. A depletion of this ozone shield would permit hazardous levels of UV solar radiation, especially in the UVB range, to bombard Earth’s surface, resulting in potentially significant effects on human health. The concern for these adverse effects intensifies if we consider that the UVB solar radiation is combined with secondary cosmic radiation (SCR) components, such as protons and muons, as well as terrestrial gamma rays. This research aims to delve into the intricate interplay between cosmic and solar radiation on earth at the cellular level, focusing on their synergistic effects on human cell biology. Through a multidisciplinary approach integrating radiobiology and physics, we aim to explore key aspects of biological responses, including cell viability, DNA damage, stress gene expression, and finally, genomic instability. To assess the impact of the combined exposure, normal i.e., non-malignant human cells (skin fibroblasts, keratinocytes, monocytes, and lymphocytes) were exposed to high-energy protons or gamma rays in combination with UVB. Cellular molecular and cytogenetic biomarkers of radiation exposure, such as DNA damage (γH2AΧ histone protein and dicentric chromosomes), as well as the expression pattern of various stress genes, were analyzed. In parallel, the MTS reduction and lactate dehydrogenase assays were used as indicators of cell viability, proliferation, and cytotoxicity. Results reveal remaining DNA damage for the co-exposed samples compared to samples exposed to only one type of radiation in all types of cells, accompanied by increased genomic instability and distinct stress gene expression patterns detected at 24–48 h post-exposure. Understanding the impact of combined radiation exposures is crucial for assessing the health risks posed to humans if the ozone layer is partially depleted, with structural and functional damages inflicted by combined cosmic and UVB exposure.

Combined radiation exposures—pairings of ionizing and non-ionizing radiation—are increasingly relevant in medical, spaceflight, and environmental contexts. This systematic review evaluates their radiobiological effects and therapeutic applications, focusing on synergistic interactions and underlying biological mechanisms. A comprehensive search of PubMed, Google Scholar, Semantic Scholar, bioRxiv, and Europe PMC identified studies published from the 1960s through 2025. Eligible studies assessed biological responses to different radiation types applied either simultaneously or within 24 h, with minor exceptions. A total of 172 studies were included and categorized into radiobiological, therapeutic, and space radiation domains. Due to the predominance of mechanistic research, no formal risk-of-bias tool was applied; methodological limitations were assessed qualitatively. Findings were synthesized narratively by radiation type and domain. Synergistic and additive effects were frequently observed, with responses influenced by dose, sequence, radiation type, and DNA repair dynamics. Therapeutic combinations often enhanced efficacy, while space radiation studies revealed multifaceted biological damage. This review provides a consolidated reference for advancing research and applications involving combined radiation exposures, emphasizing the need for mechanistic insight and standardized protocols in therapy, radiation protection, and spaceflight. This study was funded by project 21GRD02 BIOSPHERE (European Partnership on Metrology, Horizon Europe) and reported per PRISMA 2020 guidelines; no protocol was registered.

Replication stress (RS) is a hallmark of cancer, largely driven by oncogene activation. Due to high levels of RS, cancer cells depend heavily on the RS response mechanisms to avoid DNA damage. This dependency creates a therapeutic opportunity that can be exploited for more effective cancer treatment. This review synthesizes current mechanistic understanding of RS and RS response and further describes how targeted disruption of RS response proteins (ATR, Chk1, Wee1, PARP, RPA) has been used in preclinical and clinical studies. We summarize preclinical and emerging clinical evidence for exploiting RS for radiosensitization, and outline candidate biomarkers and functional assays for patient selection. We also highlight the links between RS, therapy-induced senescence and innate immune activation via the cGAS–STING (cyclic GMP-AMP synthase—Stimulator of Interferon Genes) pathway, and address current challenges and future directions.

Ionizing radiation can induce different types of DNA lesions, leading to genomic instability and ultimately cell death. Radiation therapy or radiotherapy, a major modality in cancer treatment, harnesses the genotoxic potential of radiation to target and destroy cancer cells. Nevertheless, cancer cells have the capacity to develop resistance to radiation treatment (radioresistance), which poses a major obstacle in the effective management of cancer. It has been shown that administration of platinum-based drugs to cancer patients can increase tumor radiosensitivity, but despite this, it is associated with severe adverse effects. Several lines of evidence support that activation of the DNA damage response and repair machinery in the irradiated cancer cells enhances radioresistance and cellular survival through the efficient repair of DNA lesions. Therefore, targeting of key DNA damage repair factors would render cancer cells vulnerable to the irradiation effects, increase cancer cell killing, and reduce the risk of side effects on healthy tissue. Herein, we have employed a computer-aided drug design approach for generating ab initio a chemical compound with drug-like properties potentially targeting two proteins implicated in multiple DNA repair pathways. The findings of this study could be taken into consideration in clinical decision-making in terms of co-administering radiation with DNA damage repair factor-based drugs.