Search Results (1,529)

The present study aimed to identify genes encoding enzymes involved in the biotransformation of monoterpenoid (–)-isopulegol by Rhodococcus rhodochrous IEGM 1362. This strain is able to transform (–)-isopulegol with formation of two novel metabolites with promising antitumor and analeptic activities. Cell fractions of rhodococci and specific inhibitor of cytochrome P450-dependent oxygenase activity were used to establish the localization and type of biotransformation enzymes. The expression of nine CYP450 genes selected by bioinformatics analysis was analyzed by quantitative real-time PCR (qRT-PCR). Selection of optimal reference genes for normalization of qRT-PCR results was performed using BestKeeper, Normfinder, geNorm, Delta CT, and RefFinder algorithms. As a result of these studies, the role of CYP450 enzyme complexes in the biotransformation of (–)-isopulegol was confirmed, and their cytoplasmic localization was established. The genes encoding DNA gyrase subunit B (gyrB) and protein translocase subunit A (secA) were selected as the most stable reference genes. The induced expression of the gene encoding CYP450 hydroxylase in the presence of (–)-isopulegol was determined. The obtained data allow us to identify the specific CYP450 enzyme involved in (–)-isopulegol biotransformation by R. rhodochrous IEGM 1362 and lay the foundation for further studies of molecular and genetic mechanisms of monoterpenoid biotransformation. Full article

Background: This narrative review summarizes recent progress in artificial intelligence (AI), especially radiomics and deep learning, for non-invasive diagnosis and molecular profiling of gliomas. Methodology: A thorough literature search was conducted on PubMed, Scopus, and Embase for studies published from January 2020 to July 2025, focusing on clinical and technical research. In key areas, these studies examine AI models’ predictive capabilities with multi-parametric Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET). Results: The domains identified in the literature include the advancement of radiomic models for tumor grading and biomarker prediction, such as Isocitrate Dehydrogenase (IDH) mutation, O6-methylguanine-dna methyltransferase (MGMT) promoter methylation, and 1p/19q codeletion. The growing use of convolutional neural networks (CNNs) and generative adversarial networks (GANs) in tumor segmentation, classification, and prognosis was also a significant topic discussed in the literature. Deep learning (DL) methods are evaluated against traditional radiomics regarding feature extraction, scalability, and robustness to imaging protocol differences across institutions. Conclusions: This review analyzes emerging efforts to combine clinical, imaging, and histology data within hybrid or transformer-based AI systems to enhance diagnostic accuracy. Significant findings include the application of DL to predict cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) deletion and chemokine CCL2 expression. These highlight the expanding capabilities of imaging-based genomic inference and the importance of clinical data in multimodal fusion. Challenges such as data harmonization, model interpretability, and external validation still need to be addressed. Full article

Background/Objectives: Prenatal exposure to famine can lead to lasting health effects through changes in DNA methylation. This study aims to evaluate the impact of prenatal exposure to the Chinses Great Famine (1959–1961) on human epigenome and the subsequent influence on blood lipids. Methods: We conducted an epigenome-wide association study (EWAS) of peripheral blood-based DNA methylation and prenatal exposure to the Chinese Great Famine as well as blood lipids among eight participants exposed to famine and eight sex-matched participants (born ≤ 3 years after the famine). Genome-wide DNA methylation sites were profiled using the Illumina EPIC BeadChip, which covers 850K methylation positions. Results: After EWAS analyses, seven probes in genes C8orf31, ELAVL1, U6, GBA2, SHOX2, SLC1A4, and NPHP4 reached p < 1 × 10⁻⁵. Of these, famine exposure was associated with decreased methylation levels of a GBA2 exonic probe cg08258661 (p = 4.9 × 10⁻⁶). After false discovery rate (FDR) correction, pathway enrichment analyses for genes harboring nominally significant (p < 0.05) probes identified 44 significant pathways (q < 0.05), and 5 pathways were related to lipid metabolism. After FDR correction in each pathway, probes cg02622866 (5’UTR of ATF2, p = 1.09 × 10⁻³), cg07316730 (body of GRB2, p = 1.32 × 10⁻³), and cg01105385 (body of PIK3R1, p = 1.94 × 10⁻³) in the PI2K-Akt signaling pathway were associated with blood LDL-C (q ≤ 0.04); probes cg09180702 (3’UTR of PIGQ, p = 9.21 × 10⁻⁵, and q = 0.04) and cg01421548 (body of HS3ST4, p = 5.23 × 10⁻⁵, and q = 0.01) in the metabolism pathway were associated with blood LDL-C and HDL-C, respectively; In addition, probe cg08460387 (5’UTR of MAN1C1, p = 1.09 × 10⁻⁴, and q = 0.02) in the vesicle-mediated transport pathway was associated with log-transformed blood triglycerides. Conclusions: Through an epigenetic study of the Chinese Great Famine, we identified six novel genes involved in lipid metabolism. Full article

Because of the active influx of chemical compounds into the marine environment, a significant portion is transformed and accumulates in bottom sediments (BS), posing a threat to benthic organisms. The eastern coast of the Kamchatka Peninsula, with its characteristic volcanic, seismic, and gas–chemical features, is of particular interest to our research. This study is the first to assess the cyto- and genotoxicity of BS in coastal waters off the eastern coast of the Kamchatka Peninsula using biotesting on representatives of the benthic community (the mussel Mytilus trossulus and the sand dollar Scaphehinus mirabilis). Of the aqueous extracts exposure of BS from all stations, M. trossulus showed destabilization of lysosomal membranes in gills and digestive gland cells. It was shown that aqueous extracts from BS of Kamchatka Bay (station 1) and Avachinskaya Bay (station 3) had no negative effect on DNA molecules in the gills and digestive gland cells of mussels, and the values obtained corresponded to the control. Extracts from BS of Kronotsky Bay (station 2) and Avacha Bay (station 4) damaged the integrity of the genome in the cells of the gills M. trossulus and sperm of S. mirabilis. The level of DNA damage in sperm increased by 3 and 3.5 times, respectively, compared with that in control gametes. The results of the biotests on two biological models show that sediments from Kronotsky Bay and Avacha Bay exhibit cytotoxicity and induce DNA damage in both somatic cells and gametes. Full article

Background: Cadmium (Cd) pollution poses a significant environmental challenge. Microbially induced carbonate precipitation (MICP), an advanced bioremediation approach, relies on the co-precipitation of soluble metals with the microbial hydrolysate from urea. This study isolated a urease-producing strain and evaluated its Cd remediation potential. Methods: The isolated strain UA7 was identified through 16S rDNA gene sequencing. Urease production was enhanced by optimizing the culture conditions, including temperature, dissolved oxygen levels—which were affected by the rotational speed and the design of the Erlenmeyer flask, and the concentration of urea added. Its Cd remediation efficacy was assessed both in water and soil. Results: UA7 was identified as Lysinibacillus sp., achieving peak urease activity of 188 U/mL. The immobilization rates of soluble Cd reached as high as 99.61% and 63.37%, respectively, at initial concentrations of 2000 mg/L in water and 50 mg/kg in soil. The mechanism of Cd immobilization by strain UA7 via MICP was confirmed by the microstructure of the immobilized products with attached bacteria, characteristic absorption peaks, and the formed compound Ca_0.67Cd_0.33CO₃, which were analyzed using scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction (XRD). The Cd-remediation effect of strain UA7, which reduces lodging in wheat plants, prevents the thinning and yellowing of stems and leaves, and hinders the transition of soluble Cd to the above-ground parts of the plant, was also demonstrated in a pot experiment. Conclusions: Therefore, Lysinibacillus sp. UA7 exhibited high potential for efficiently remediating contaminated Cd. Full article

This study presents the development of an advanced three-dimensional (3D) bioprinted skin scaffold integrating sodium alginate (SA), gelatin (Gel), human skin-derived decellularized extracellular matrix (dECM), and microbiota-derived postbiotics. To ensure a biocompatible and functional ECM source, human skin samples collected during elective aesthetic surgical procedures were utilized. Following enzymatic treatment, the dermal layer was carefully separated from the epidermis and subjected to four different decellularization protocols. Among them, Protocol IV emerged as the most suitable, achieving significant DNA removal while maintaining the structural and biochemical integrity of the ECM, as confirmed by Fourier-transform infrared spectroscopy. Building on this optimized dECM-4, microbiota-derived postbiotics from Limosilactobacillus reuteri EIR/Spx-2 were incorporated to further enhance the scaffold’s bioactivity. Hybrid scaffolds were then fabricated using 7% Gel, 2% SA, 1% dECM-4, and 40 mg/mL postbiotics in five-layered grid structures via 3D bioprinting technology. Although this composition resulted in reduced mechanical strength, it exhibited improved hydrophilicity and biodegradability. Moreover, antimicrobial assays demonstrated inhibition zones of 16 mm and 13 mm against methicillin-resistant Staphylococcus aureus (MRSA, ATCC 43300) and Pseudomonas aeruginosa (ATCC 27853), respectively. Importantly, biocompatibility was confirmed through in vitro studies using human keratinocyte (HaCaT) cells, which adhered, proliferated, and maintained normal morphology over a 7-day culture period. Taken together, these findings suggest that the engineered hybrid scaffold provides both regenerative support and antimicrobial protection, making it a strong candidate for clinical applications, particularly in the management of chronic wounds. Full article

Background: Lung cancer remains the leading cause of cancer-related mortality globally, largely due to delayed diagnosis in its early stages. While conventional diagnostic tools like low-dose CT and tissue biopsy are routinely used, they suffer from limitations including invasiveness, radiation exposure, cost, and limited sensitivity for early-stage detection. Liquid biopsy, a minimally invasive alternative that captures circulating tumor-derived biomarkers such as ctDNA, cfRNA, and exosomes from body fluids, offers promising diagnostic potential—yet its sensitivity in early disease remains suboptimal. Recent advances in Artificial Intelligence (AI) and radiomics are poised to bridge this gap. Objective: This review aims to explore how AI, in combination with radiomics, enhances the diagnostic capabilities of liquid biopsy for early detection of lung cancer and facilitates personalized monitoring strategies. Content Overview: We begin by outlining the molecular heterogeneity of lung cancer, emphasizing the need for earlier, more accurate detection strategies. The discussion then transitions into liquid biopsy and its key analytes, followed by an in-depth overview of AI techniques—including machine learning (e.g., SVMs, Random Forest) and deep learning models (e.g., CNNs, RNNs, GANs)—that enable robust pattern recognition across multi-omics datasets. The role of radiomics, which quantitatively extracts spatial and morphological features from imaging modalities such as CT and PET, is explored in conjunction with AI to provide an integrative, multimodal approach. This convergence supports the broader vision of precision medicine by integrating omics data, imaging, and electronic health records. Discussion: The synergy between AI, liquid biopsy, and radiomics signifies a shift from traditional diagnostics toward dynamic, patient-specific decision-making. Radiomics contributes spatial information, while AI improves pattern detection and predictive modeling. Despite these advancements, challenges remain—including data standardization, limited annotated datasets, the interpretability of deep learning models, and ethical considerations. A push toward rigorous validation and multimodal AI frameworks is necessary to facilitate clinical adoption. Conclusion: The integration of AI with liquid biopsy and radiomics holds transformative potential for early lung cancer detection. This non-invasive, scalable, and individualized diagnostic paradigm could significantly reduce lung cancer mortality through timely and targeted interventions. As technology and regulatory pathways mature, collaborative research is crucial to standardize methodologies and translate this innovation into routine clinical practice. Full article

Plants from the Brassicaceae family are characterized by their high content of glucosinolates (GSLs), whose hydrolysis products, isothiocyanates (ITC) or indole compounds, have been found to have anti-inflammatory, antioxidant and metabolic regulatory functions. In this work, we used a model of transformation using the MCF10A cell line, a non-tumorigenic breast fibrocystic disease cell line, treated with benzo(a)pyrene (B(a)P), a potent carcinogen known to induce the production of reactive oxygen species (ROS) and DNA damage. Broccoli sprout (BSE) or red cabbage aqueous (RCA) extracts were rich in ITC and indole compounds. Their use decreased B(a)P induced cellular proliferation and ROS production. in addition, RCA extract induced autophagy in MCF10A cells. Our results indicate a potential use of BSE or RCA for the prevention of carcinogen-induced transformation and of RCA as a method for autophagy, a tumor suppressor pathway, induction. Full article

Therapy resistance is a major obstacle to cancer treatment, and transforming growth factor-beta (TGF-β) signaling has emerged as a major instigator across many cancer types and therapeutic regimens. Solid tumors overexpress TGF-β ligands, and canonical and non-canonical TGF-β signaling pathways drive molecular changes in most cell types within the tumor to hijack therapeutic responses. Cancer therapies further stimulate TGF-β release to potentiate this problem. Molecular mechanisms of TGF-β action supporting resistance include upregulation of drug efflux pumps, enhanced DNA Damage Repair, elaboration of stiffened extracellular matrix, and decreased neoantigen presentation. TGF-β also activates pro-survival pathways, such as epidermal growth factor receptor, B-cell lymphoma-2 expression, and AKT-mTOR signaling. TGF-β-induced epithelial-to-mesenchymal transformation leads to tumor heterogeneity and acquisition of stem-like states. In the tumor microenvironment, TGF-β induces extracellular matrix production, contractility, and secretion of immunosuppressive cytokines by cancer-associated fibroblasts that contribute to drug resistance. TGF-β also blunts cytotoxic T and NK cell activities and stimulates recruitment and differentiation of immunosuppressive cells, including T-regulatory cells, M2 macrophages, and myeloid-derived suppressor cells. The importance of TGF-β signaling in development of drug resistance cannot be understated and should be further explored mechanistically to identify novel molecular approaches and combinatorial drug dosing strategies to prevent drug-resistance. Full article

Biomolecule-driven smart materials represent a paradigm shift in pharmacology, transitioning drug delivery from a passive process to an active, programmable, and highly specific intervention. These systems, constructed from or functionalized with biological macromolecules such as nucleic acids, peptides, proteins, and polysaccharides, are engineered to sense and respond to specific pathophysiological cues or external triggers. This review provides a comprehensive analysis of this rapidly evolving field. We first delineate the fundamental principles of stimuli-responsive actuation, categorizing systems based on their response to endogenous (pH, redox, enzymes, ROS) and exogenous (temperature, light, magnetic fields) triggers. We then conduct an in-depth survey of the primary biomolecular architectures, examining the unique design space offered by DNA nanotechnology, the functional versatility of peptides and proteins, and the biocompatibility of polysaccharides. Key therapeutic applications in oncology, inflammatory diseases, and gene therapy are discussed, highlighting how these intelligent systems are being designed to overcome critical biological barriers and enhance therapeutic efficacy. Finally, we address the formidable challenges—spanning biocompatibility, manufacturing scalability, and regulatory navigation—that constitute the “bench-to-bedside” chasm. We conclude by exploring future perspectives, including the development of multi-stimuli responsive, logic-gated systems and the transformative potential of artificial intelligence in designing the next generation of personalized nanomedicines. Full article

Expanding the chemical space of DNA-encoded libraries (DELs) is desirable for identifying novel bioactive compounds and enhancing hit quality in affinity-based screening. In this study, we designed and synthesized a new on-DNA diazide platform (DAP) molecule that incorporates both aromatic and aliphatic azido groups within a single scaffold. These orthogonal azides exhibit distinct reactivity profiles, enabling a stepwise warhead construction strategy through chemoselective transformations. This approach facilitates greater structural diversity and efficient incorporation of diverse building blocks. A virtual DEL was generated based on this DAP scaffold, and its chemical space was compared with that of bioactive compounds in the ChEMBL database. The analysis revealed that this virtual library occupied a distinct and previously unexplored region of chemical space, highlighting the potential of this DAP-based strategy for discovering structurally novel DEL members with biological relevance. Full article

Placental dysfunction underlies the major obstetric syndromes, including preeclampsia, fetal growth restriction, placenta accreta spectrum, pregnancy loss, and monochorionic twin complications. Recent molecular studies have revealed that dysregulated oxygen sensing, impaired angiogenic signaling, altered immune tolerance, and defective trophoblast fusion represent shared pathogenic pathways that converge across these disorders. Integrating morphological evidence with mechanistic data highlights how villous maldevelopment, shallow trophoblast invasion, and aberrant vascular remodeling translate into clinical disease. Advances in biomarker research have already transformed clinical care: the sFlt-1/PlGF ratio is now established in the prediction and management of preeclampsia, while placental proteins such as PAPP-A and PP13, nucleic acid signatures including cfDNA, cfRNA and miRNAs, and extracellular vesicle cargo show promising potential for early, non-invasive detection of placental pathology. Multi-omics approaches, particularly single-cell and spatial transcriptomics combined with proteomic and metabolomic profiling, are paving the way for composite diagnostic panels that capture the polygenic and multicellular nature of placental disease. This review synthesizes current knowledge of molecular mechanisms, histological correlates, and translational biomarkers, and outlines how precision obstetrics may emerge from bridging mechanistic discoveries with clinical applications. Full article

In the marine environment, plastic fragments are constantly engaged in a complex degradation process under exposure to various physical and chemical factors, one of which is ultraviolet (UV) radiation. These processes result in the formation of smaller micro- and nano-sized plastic particles, which are highly bioavailable to marine organisms. To clarify the toxicological effects of the exposure of degraded plastic on the marine organisms, the model used in this study was the Pacific mussel Mytilus trossulus and polymethylmethacrylate (PMMA), which is commonly found in marine debris. Using molecular and biochemical markers (DNA damage, lysosomal membrane stability, integral antiradical activity (IAA) of biological samples, and malondialdehyde (MDA) as a product of lipid peroxidation), the toxicity of pristine PMMA and photoaged (PMMA-UV) particles was assessed. Using Fourier transform infrared spectroscopy, the characteristics of the macromolecular changes in the chemical structure of PMMA-UV were obtained, with an oxidation index of 6.83 ± 0.46, compared to the pristine PMMA of 5.15 ± 0.54. Using a laser analyzer, the sizes of PMMA particles were determined, and it was found that after UV irradiation, the ratio of size groups changed—the proportion of particles with sizes of 500–1000 μm decreased, and the number of particles with sizes of 50–125 μm increased twofold. Analysis of mussel cell viability showed that after exposure to both types of PMMA microparticles, there was a decrease in the ability to retain neutral red dye in lysosomes: PMMA and PMMA-UV had a similar effect on hemocytes, reducing dye retention in cells to 55.2 ± 3.24% and 61.1 ± 1.99%, respectively. In gill and digestive gland cells, PMMA-UV particles reduced the stability of lysosomal membranes to a greater extent than PMMA. After PMMA and PMMA-UV particle exposure, the levels of DNA damage were as follows: in hemocytes, 10.1 ± 1.4% and 12.7 ± 0.8%, respectively; in gills, 7.8 ± 1.1% and 14.4 ± 2.9%, respectively; and in the digestive gland, 19.0 ± 1.3% and 21.9 ± 2.8%, respectively, according to the control values 3.6 ± 1.3%, 4.6 ± 1.1%, 5.1 ± 1.5%, respectively. According to the results of biochemical markers, the reaction of mussels to the presence of PMMA and PMMA-UV particles in the environment was tissue-specific: in the cells of the digestive gland, the level of IAA increased by 2 and 1.3 times compared to the control group of mussels (76.22 ± 6.77 nmol trolox/g wet weight and 52.43 ± 2.36 nmol trolox/g wet, respectively), while in the gill cells, the non-significant increase in antiradical activity was noted. An increase in MDA content was also observed in gill cells (255.8 ± 9.12 nmol MDA/g wet weight and 263.46 ± 9.45 nmol MDA/g wet weight, respectively) compared with the control group. This study showed that UV irradiation of PMMA microparticles increases their bioavailability and toxicity to M. trossulus. Full article

Despite ongoing advancements in the field of heart failure, heart transplantation remains the definitive treatment for patients with advanced heart failure. Decades of research, surgical innovation, and progress in transplant immunology have enabled the overcoming of persistent challenges associated with this complex procedure. Since the initial preclinical experiments involving heart transplants in canines and primates, the process has been profoundly transformed through the development of the bioptome for endomyocardial biopsies and the introduction of immunosuppressive therapies. More recently, improvements in the preservation and transportation of donor hearts, as well as the utilization of cell-free DNA for evaluating graft rejection, are laying the groundwork for further advancements in non-invasive rejection diagnosis and the expansion of the donor pool. Full article

DNA methylation holds promise for the early detection of tissue damage, making it crucial for identifying polycyclic aromatic hydrocarbon (PAH)-associated epigenetic biomarkers in childhood asthma. Sulforaphane (SFN), as a potential epigenetic modulator, can alleviate the adverse effects of environmental pollutants. This study quantified serum PAHs in 370 children via gas chromatography–mass spectrometry, assessed the methylation of target genes using bisulfite sequencing PCR (BSP), and performed mediation analysis to estimate the mediating effects of methylation levels between PAHs and childhood asthma. Murine models exposed to PAHs prenatally or postnatally, with offspring challenged with ovalbumin (OVA), were analyzed for lung DNA methylation. In vitro, HBE cells and HBSMCs treated with benzo(a)pyrene (BaP) and/or SFN were tested for inflammatory cytokines, methylation-related enzymes, and matrix metallopeptidase 9 (MMP9) modifications. The results showed total PAHs were associated with childhood asthma, with mediating effects of long interspersed nuclear element-1 (LINE-1) methylation. Prenatal PAH exposure enriched differentially methylated genes in the extracellular matrix (ECM)-receptor interaction pathway, while postnatal exposure enriched those in purine metabolism, and postnatal exposure also elevated Mmp9 expression via hypomethylation. BaP increased the expression of interferon gamma (IFN-γ), interleukin-4 (IL-4), interleukin-17A (IL-17A), transforming growth factor beta 1 (TGF-β), and ten-eleven translocation methylcytosine dioxygenases (TETs), and it upregulated MMP9 via enhancer hypomethylation and H3K27ac enrichment, while SFN reversed these effects by downregulating histone methyltransferase (HMT), leading to reduced H3K4me1 and subsequent H3K27ac depletion, thus suppressing MMP9 transcription. This study demonstrates that DNA methylation mediates PAH–childhood asthma associations, with distinct patterns in different exposure windows; MMP9 could serve as a crucial target for epigenetic modification during lung inflammation induced by PAH exposure, and SFN reverses PAH-induced epigenetic changes, aiding prevention strategies. Full article