Molecular imaging in preclinical research using PET and SPECT has become a key component of contemporary biomedicine, enabling noninvasive, quantitative, and longitudinal assessment of biological processes in vivo. Rapid technological progress, including advances in detector design, readout electronics, reconstruction algorithms, and multimodal integration, has substantially improved spatial resolution, sensitivity, and quantitative accuracy, thereby enhancing the translational value of animal models. PET and SPECT enable precise characterization of metabolic, molecular, and functional alterations across a wide range of diseases including cancer, cardiovascular disorders, neurodegeneration, and inflammation. Radiopharmaceuticals targeting diverse biological pathways, combined with PET and SPECT systems, allow comprehensive and physiologically relevant evaluation of disease mechanisms and therapeutic responses. Despite these significant advances, important challenges remain, including limitations in quantitative precision, partial-volume effects and inter-laboratory variability in experimental protocols. An additional limitation is the lack of globally standardized quality-control and calibration procedures tailored to preclinical imaging systems. Emerging multimodal imaging platforms and high-fidelity disease models, such as genetically engineered rodents, large animals, and zebrafish, continue to enhance reproducibility, biological relevance, and translational potential. This review summarizes the development, capabilities, and limitations of preclinical PET and SPECT imaging, highlighting their expanding role in advancing molecular diagnostics, radiopharmaceutical development, and translational medicine in both preclinical studies and early-phase clinical research.

Epigenetics encompasses heritable but reversible modifications of gene expression that occur without changes in the DNA sequence and involve mechanisms such as DNA and RNA methylation and histone modifications. These mechanisms modulate chromatin architecture, genome stability, and cellular responses to environmental stressors, and their dysregulation contributes to oncogenesis and cancer progression. In parallel, radiotherapy remains a cornerstone of cancer treatment; furthermore, ionizing radiation induces epigenetic modifications alongside direct DNA double-strand breaks and oxidative damage. Radiation-induced epigenetic changes, including global or locus-specific DNA methylation shifts (e.g., genes promoter CpG islets), histone acetylation and methylation imbalances, are increasingly recognized as key contributors to molecular radioresistance. These adaptive responses may enhance tumor cell survival, affect therapeutic efficacy, and promote metastasis. Understanding the interplay between radiation exposure and epigenetic remodeling opens new perspectives for precision oncology and diagnostics. Epigenetic biomarkers hold potential for predicting treatment response and prognosis, while epigenetic modifiers may sensitize tumors to radiation. This review summarizes current evidence on radiation-induced epigenetic mechanisms and evaluates their diagnostic, prognostic, and therapeutic implications in cancer management.

Pancreatic cancer is characterized by cellular heterogeneity, contributing to variable responses to anticancer treatment. Natural products may modify these responses in a context-dependent manner. We investigated whether three Lepidium meyenii Walp. (Brassicaceae; maca) preparations, marked as yellow (MY), red (MR), and black (MB), differentially modify pancreatic cancer cell responses to doxorubicin (DOX). BxPC-3, MIA PaCa-2, and PANC-1 cells were treated with maca preparations alone or combined with DOX. Cell viability, apoptosis-associated signaling, survival-related proteins, lipid droplet accumulation, and lipid metabolism-related proteins were evaluated. Drug interactions were assessed using Bliss independence and Highest Single Agent (HSA) models. Interaction profiles differed among cell lines and depended on the tested maca preparation and DOX concentration. The strongest favorable interactions were observed in PANC-1 cells treated with MR or MB plus 2.5 µM DOX (Bliss/HSA scores: 18.9/13.1 and 17.6/12.4, respectively), whereas BxPC-3 cells showed favorable interactions with MY, MR, and MB at 5 µM DOX (Bliss/HSA scores: 12.4/9.8, 10.7/8.5, and 11.9/9.2, respectively). MIA PaCa-2 cells showed mainly neutral or less-than-additive interactions. These responses were accompanied by changes in caspase-3 activation, PI3K, FAP, and FOXO1 protein levels, lipid droplet accumulation, and ATGL, ABHD5, and PLIN3 levels. Overall, the tested MY, MR, and MB preparations differentially modified pancreatic cancer cell responses to DOX and were associated with distinct survival-related and lipid metabolism-related changes. Further phytochemical characterization and functional mechanistic studies are required to identify the constituents involved and determine whether the observed molecular changes contribute causally to these effects.

Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM-1) is a platelet receptor recognized as a negative regulator of platelet activity. During thrombus formation, platelets differentiate into distinct populations, but whether CEACAM-1 is preferentially associated with specific platelet phenotypes remains unclear. Here, we investigated CEACAM-1 localization in different platelet populations, focusing on the accessibility of its extracellular domain. In platelets adherent to poly-L-lysine, the CEACAM-1 signal was predominantly intracellular and decreased following treatment with acetylsalicylic acid (ASA), whereas glucose increased this signal. During integrin-dependent spreading on fibrinogen, CEACAM-1 was undetectable by immunofluorescence, irrespective of αIIbβ3 inhibition with tirofiban, although its presence was confirmed by Western blotting. Flow cytometry revealed that ASA reduced the percentage of CEACAM-1-positive platelets following ADP stimulation under both normoglycemic and hyperglycemic conditions. Confocal microscopy demonstrated co-localization of CEACAM-1 with phosphatidylserine (PS)-positive regions, a hallmark of the procoagulant platelet phenotype. In thrombi formed on collagen fibers under flow, ASA reduced the CEACAM-1-positive area under both conditions. However, a reduction in the ratio of CEACAM-1-positive area to PS-exposing area was observed only under normoglycemic conditions. In fibrin–platelet clots, CEACAM-1 was detected only after prolonged clot incubation and subsequent platelet permeabilization. Collectively, these findings reveal differences in CEACAM-1 localization and detectability across platelet populations and experimental settings, suggesting an association with platelet functional specialization.

More than 30% of diabetic patients develop dermatopathies linked to inflammation and increased vascular permeability. Considering the role of the renin–angiotensin–aldosterone system (RAAS) in diabetic complications, this study examined whether aldosterone (ALDO) and the mineralocorticoid receptor (MR) contribute to diabetes-related skin microangiopathy. Vascular permeability was measured in normoglycemic rats and insulin-dependent (streptozotocin-induced) diabetic rats. The expression of MR, 11β-hydroxysteroid dehydrogenase type 2 (HSD11β2), vascular endothelial growth factor (VEGF), von Willebrand factor (vWF), and the tight junction protein ZO-1 was determined by PCR and immunohistochemistry. Diabetic rats received the MR antagonist eplerenone (EPL, 100 mg/kg) for 10 days. Additionally, the effects of ALDO and EPL on endothelial permeability were evaluated in human dermal microvascular endothelial cells (HMEC-1) using a Transwell system. Diabetic rats showed skin atrophy, collagen damage, elevated ALDO levels, reduced MR and HSD11β2 expression, and increased vascular permeability, along with upregulation of VEGF and vWF. EPL markedly reduced these abnormalities. In vitro, ALDO increased endothelial permeability under hyperglycemia, and EPL counteracted this effect. These findings indicate that activation of the ALDO/MR pathway promotes skin vascular permeability in diabetes through VEGF- and vWF-dependent mechanisms. MR blockade limits these changes, suggesting therapeutic potential in preventing diabetes-associated skin complications.

Prostate cancer progression and therapy response are strongly influenced by the tumor microenvironment (TME), particularly stromal fibroblasts that regulate survival signaling, metabolism, and drug resistance. In this study, we investigated whether extracts from three Lepidium meyenii (maca) morphotypes, yellow (MY), red (MR), and black (MB), modulate doxorubicin (DOX) responses in 22Rv1 prostate cancer cells under mono-culture and co-culture conditions with human dermal fibroblasts (HDFa). Cell viability, proliferation, apoptosis-related proteins, lipid droplets (LDs) accumulation, and selected signaling markers were analyzed. In mono-culture, maca extracts exhibited limited cytotoxicity, with MB showing the strongest but still moderate effect. Co-treatment with DOX did not enhance cytotoxicity and resulted in context-dependent modulation of caspase-3 and caspase-8. In co-culture, HDFa cells reduced DOX sensitivity, suggesting altered treatment responses under co-culture conditions. Morphometric analysis suggested fibroblast activation-like changes. Across models, maca reduced LDs accumulation, while increased adipose triglyceride lipase (ATGL) levels in co-culture suggested altered lipid utilization. Additionally, maca extracts modulated PI3K, PSMA, FOXO1, FAP, and HAT1 in a morphotype-dependent manner. Overall, maca extracts acted primarily as context-dependent modulators of signaling and lipid metabolism markers rather than direct cytotoxic agents with their effects strongly dependent on both extract type and microenvironmental context.