Search Results (32,677)

Τhe intrauterine environment has a strong connection with the growing fetus and possible effects that can continue up to adulthood. Currently, stress is conceptualized as a modern teratogen. The overwhelming majority of studies indicate that maternal stress during pregnancy may have effects on pregnancy outcomes and fetal development, with long-lasting consequences on child and adult vulnerability to disease. Glucocorticoids are essential for regulating fetal development, growth, and metabolism. The two isoforms of 11beta-hydroxysteroid dehydrogenase enzyme (11β-HSD) mediate and regulate glucocorticoid actions and biological activity. It has not yet been fully elucidated whether maternal stress during pregnancy affects 11β-HSD isoenzyme activity and expression and results in possible adverse effects on fetal development, metabolism, and pregnancy outcomes. This review examines a possible pathophysiological mechanism by which maternal stress during pregnancy affects placental 11β-HSD isoenzyme activity, thereby causing adverse effects on the physiological status of pregnancy, fetal development, and metabolism. Furthermore, the main outcome of the review is the following: chronic and acute maternal stress during pregnancy affects the activity and the expression of placental 11β-HSD isoenzymes and has possible subsequent unfavorable results on preeclampsia, preterm birth, and fetuses with intrauterine growth restriction (IUGR) or small for gestational age (SGA) fetuses. Full article

Fucoxanthin (Fx), a marine xanthophyll carotenoid, has attracted considerable scientific attention due to its wide-ranging biological activities, including antioxidant, anti-inflammatory, anti-obesity, and anticancer effects. Despite its substantial therapeutic potential, the clinical application of Fx and its derivatives remains constrained by their structural complexity, low chemical stability, and limited bioavailability. This review offers a thorough and up-to-date overview of Fx, encompassing its primary natural sources, the metabolic biotransformation to fucoxanthinol (FxOH) and amarouciaxanthin A—metabolites whose bioactive properties significantly contribute to the observed in vivo effects—and the molecular mechanisms underlying the biological activities of Fx and its metabolites, with emphasis on their modulation of key intracellular signalling pathways involved in inflammation, lipid metabolism, and cell proliferation. Furthermore, it explores how targeted structural modifications may enhance the pharmacokinetic profiles and expand the therapeutic potential of Fx-based compounds, while highlighting promising strategies for their optimisation. By integrating insights from pharmacology, biochemistry, and synthetic chemistry, this work aims to guide future efforts in the rational design of marine-derived bioactive agents and underscores the value of marine biodiversity in therapeutic innovation. Full article

Schlafen (SLFN) proteins are a unique and emerging yet incompletely understood family that have primarily been investigated for their putative roles in immunological responses, cell proliferation, and non-malignant cell differentiation. Increasingly, SLFNs have been implicated in diverse biological and pathological contexts, including cancers, viral replication, embryonic lethality, meiotic drive, and inflammatory bowel diseases, where they may be either genetically upregulated or downregulated. In recent years, novel insights into their functional similarities and distinctive particularities have intensified interest in this gene family. This review critically evaluates the biology of SLFN proteins with a specific focus on the epigenetic regulation of their expression and the differential methods by which they regulate downstream proteins. Evidence indicates that SLFNs act not only as regulators of transcription but also as modulators of gene expression through post-transcriptional modifications and epigenetic mechanisms, which demonstrate their multifaceted and context-dependent activity across disease models. By consolidating these findings, this review brings to light the physiological and pathological significance of SLFNs and identifies key gaps in understanding their epigenetic control and mechanistic diversity, thereby offering directions for future research. Full article

Background: Diabetic retinopathy (DR), a leading cause of blindness, lacks early biomarkers and mechanism-targeted therapies. While oxidative stress drives DR pathogenesis, the role of oxeiptosis—a reactive oxygen species-induced, caspase-independent cell death pathway—remains largely unexplored. Methods: We integrated transcriptomic profiling (GSE221521: 69 DR vs. 50 controls), two-sample Mendelian randomization (MR) using blood cis-eQTLs (GTEx) as instruments and DR GWAS (FinnGen R12) as outcome, machine learning-based feature selection (SVM-RFE and Boruta algorithms), and single-cell RNA sequencing (scRNA-seq) analysis (GSE165784). Functional enrichment, immune deconvolution (CIBERSORT), and diagnostic nomogram construction were performed. We validated the key genes using human retinal microvascular endothelial cells (hRMECs) treated with high glucose (30 mM). Results: Oxeiptosis scores were elevated in DR blood samples (p < 0.001). MR analysis identified five putative causal genes: CASP2 (OR = 1.067), PLEC (OR = 1.035) and FBN2 (OR = 1.016) as risk factors, and CYP27A1 (OR = 0.960) and GPD2 (OR = 0.958) as protective factors. SVM-RFE and Boruta algorithms confirmed CASP2 and PLEC as hub genes. A nomogram incorporating both genes achieved robust DR prediction (AUC = 0.811). Functional analysis associated these genes with innate immune activation and extracellular matrix reorganization. Single-cell transcriptomics revealed PLEC was markedly overexpressed in disease-relevant cells (fibroblasts, endothelial cells), whereas CASP2 exhibited a distinct pattern, with notable enrichment in retinal CD8+ T cells. Both genes were associated with a pro-inflammatory shift in the immune landscape. Their upregulation was validated in independent datasets and high-glucose-stressed retinal cells. Conclusions: This study establishes an integrated multi-omics framework implicating oxeiptosis-related pathways in DR and nominates CASP2 and PLEC as putatively causal, biologically relevant candidate biomarkers and potential therapeutic targets. Full article

Alzheimer’s disease continues to be one of the most urgent neurodegenerative conditions, with acetylcholinesterase (AChE) inhibitors serving as a fundamental component of contemporary treatment approaches. Growing evidence underscores that marine ecosystems are a rich source of structurally varied and biologically active natural products exhibiting anticholinesterase properties. This review presents a thorough synthesis of marine-derived metabolites—including those sourced from bacteria, fungi, sponges, algae, and other marine life—that demonstrate inhibitory effects against AChE and butyrylcholinesterase (BuChE). Numerous compounds, such as meroterpenoids, alkaloids, peptides, and phlorotannins, not only show nanomolar to micromolar inhibitory activity but also reveal additional neuroprotective characteristics, including antioxidant effects, anti-amyloid properties, and modulation of neuronal survival pathways. Despite these encouraging findings, the transition to clinical applications is hindered by a lack of comprehensive pharmacokinetic, toxicity, and long-term efficacy studies. The structural variety of marine metabolites provides valuable frameworks for the development of next-generation cholinesterase inhibitors. Further interdisciplinary research is essential to enhance their therapeutic potential and facilitate their incorporation into strategies for addressing Alzheimer’s disease and related conditions. Full article

This review critically surveys the emerging integration of Surface-Enhanced Raman Scattering (SERS) with photonic-crystal fibers (PCFs) for chemical and biological detection, an area still scarce in the literature. SERS exploits electromagnetic and chemical enhancement to overcome the intrinsic weakness of Raman scattering, while PCF offers low transmission loss and a strong evanescent field that further amplify the signal. The structural designs of PCF, encompassing solid-core and hollow-core variants, are discussed and their respective advantages in different sensing scenarios are presented. Applications in chemical detection, biomedicine, and explosive identification are detailed, demonstrating the versatility and potential of PCF-SERS sensors. Future efforts will focus on robust PCF geometries that guarantee stable and reproducible signals, AI-driven spectral algorithms, hybrid fibre architectures and scalable manufacturing. These advances are expected to translate PCF-SERS from bench-top demonstrations to routine deployment in environmental monitoring, clinical diagnostics and food-safety control. Full article

Chronic pain conditions are debilitating and have an enormous impact on quality of life, yet underlying biological mechanisms remain poorly understood, hindering the development of diagnostic tools and effective treatments. Emerging evidence suggests a role for immune dysfunction in chronic pain. Among the various forms of immune dysfunction, T cell exhaustion and senescence, well-characterized in cancer and chronic infections, remain largely unexplored in chronic pain research. At the same time, lifestyle factors such as sleep, stress, physical activity, and diet are increasingly recognized as modulators of both pain and immune function. This review explores the potential interplay between these behavioural factors, immune exhaustion/senescence, and chronic pain. Critical gaps in current knowledge are identified, and future directions are outlined to clarify immune dysfunction and the influence of lifestyle factors in chronic pain conditions. Full article

Gastric cancer (GC) remains a major cause of cancer-related mortality, with limited options for early detection and precision therapy. Collagen family members are increasingly recognized as key structural and regulatory components of the tumor microenvironment. Collagen type X alpha 1 chain (COL10A1) appears among the top overexpressed genes in GC and has been linked with tumorigenesis, but its functional role in GC has not been completely elucidated. The oncogenic potential of COL10A1 was assessed in vitro in GC cell lines using adenoviral-mediated overexpression. Functional assays were further performed to evaluate proliferation, apoptosis, migration, invasion, and epithelial–mesenchymal transition (EMT) markers. Intracellular signaling alterations were analyzed by phosphokinase protein profiling and protein–protein interaction network analysis. COL10A1 overexpression significantly increased proliferation and migration, while reducing GC cell apoptosis. It promotes EMT by up-regulating mesenchymal markers (N-cadherin, Vimentin, Snail/Slug) and suppressing epithelial markers such as E-cadherin and β-catenin. Additionally, COL10A1 overexpression activated oncogenic signaling pathways, including the JNK and MAPK cascades, increasing proliferation and tumorigenic potential. Our results showed that COL10A1 functions as a driver for tumor progression by promoting proliferation, migration, and invasion along with EMT through activation of important oncogenic pathways. These findings highlight its biological role in tumor progression and contribute to a better understanding of GC pathogenesis. Full article

Background: The integration of radiotherapy (RT) and immunotherapy (IO) is transforming oncologic paradigms by combining local tumor control with systemic immune activation. In urological cancers—prostate, bladder, and renal cell carcinoma—this strategy is supported by growing biological rationale and promising early clinical results. Methods: This narrative review synthesizes preclinical and clinical evidence on RT–IO combinations in urological malignancies. A comprehensive literature search was performed in PubMed, Embase, and ClinicalTrials.gov, focusing on mechanistic insights, clinical trials, and translational challenges related to RT–IO synergy. Results: Early-phase studies in bladder and renal cell carcinoma demonstrate feasibility, immunogenic enhancement, and manageable toxicity when RT is combined with checkpoint inhibitors. Prostate cancer remains less immunoresponsive but may benefit from RT-induced immune priming, particularly in biomarker-enriched subgroups. Innovations in precision RT, biomarkers, artificial intelligence, and novel immunotherapeutics are shaping future applications. Conclusions: RT–IO combinations represent a promising yet complex frontier in urological oncology. Future success will rely on precision-guided patient selection, optimized trial design, and equitable global implementation to ensure durable clinical benefit. Full article

The problem of steroid hormones in the aquatic environment remains a current global research topic. These substances have a strong impact on biological processes, contributing to reductions in the populations of numerous fish and amphibian species. The impact of steroid hormones, especially the third-generation progestogens, on aquatic invertebrates is poorly understood. We aimed to determine whether desogestrel, progestogen of low androgenic activity, affects the reproduction and growth of the following freshwater invertebrates: snails of the species Melanoides tuberculata and the planarian Dugesia sp. We also tried to estimate the threshold concentrations of this substance at which significant changes in both the behavior and reproductive activity of the studied organisms are observed. In the mesocosm experiment, we performed three treatments with the following different concentrations of desogestrel: control 0 ng/L, medium 10 ng/L, and high 100 ng/L. The high hormone concentration significantly reduced the reproduction of both snails and planarians, despite their different life history strategies, compared to the control. Both planarians and snails showed a significantly lower abundance in the high concentration compared to the 10 ng/L treatment, indicating a threshold concentration > 10 ng/L. The impacts of steroid hormone pollution on aquatic organisms and the need for further research are discussed. Full article

Epilobium parviflorum Schreb. is used in folk and modern medicine for the treatment of prostate diseases. It is also known to alleviate gastrointestinal ailments. The aim of the present study is to define the chemical composition of diverse extracts from the herb, to test their inhibitory properties toward post-proline-specific peptidases and to elucidate the mechanisms of their antitumor activity on colorectal carcinoma cells in vitro. The extractions were performed using mono- or biphasic systems of solvents. Their chemical compositions were defined by LC-HRMS. Inhibitory properties towards prolyloligopeptidase (POP) and fibroblast activation protein (FAP) were studied by kinetic assays on human recombinant enzymes. Antioxidant activity was measured by three methods. Genotoxicity to HT-29 colorectal carcinoma cells was analyzed with the comet assay. FACS analyses and flow cytometry were used to evaluate the extracts effect on the cell cycle and their pro-apoptotic properties on HT-29 cells. The extract derived using 80% ethanol was chosen for the next studies due to its efficient and selective inhibition of POP. It contains mainly oenotein B and myricetin-3-O-rhamnoside. Its antioxidant and moderate genotoxic activities can contribute to the antitumor effect on HT-29 cells. The extract has a small effect on the cell cycle but a pronounced pro-apoptotic action on those cells. In conclusion, the 80% ethanol extract of E. parviflorum concentrates the ellagitannin oenotein B, which is a selective inhibitor of POP. Antitumor activity of the extract towards HT-29 cells may be due to the inhibition of POP, the antioxidant, genotoxic and pro-apoptotic activities. Full article

Salinomycin and monensin represent a class of natural ionophore antibiotics with strong anticancer properties. In this paper we report on chemical modification of these compounds by conjugation with phosphonium cations for targeting conjugates to the mitochondria of cancer cells. Our findings indicate that this approach yields conjugates with enhanced anticancer activity and selectivity, outperforming not only the parent compounds but also the widely used chemotherapeutic agent, doxorubicin. Comprehensive biological and biophysical analyses proved that the conjugates target the mitochondria in cancer cells, with some of the derivatives additionally promoting generation of mitochondrial reactive oxygen species (mtROS). This targeted strategy holds significant promise for the development of effective mitochondrial-targeted novel anticancer agent. Full article

Phosphate tailings (PTs) are typical industrial byproducts that can rapidly neutralize soil acidity. However, their acid-neutralizing efficacy, long-term application optimization mechanisms, and high-yield regulation pathways for crops remain unclear. This study conducted a corn-potato crop rotation field trial on acidic soils, investigating the effect of different PT application rates (T: CK, 0 t·ha⁻¹; PTs-1, 6 t·ha⁻¹; PTs-2, 9 t·ha⁻¹; PTs-3, 15 t·ha⁻¹) in a multiple cropping system (C: late autumn potatoes (LAP)-early spring potatoes (ESP)-summer maize (SM)). The results showed that two consecutive applications of 9 t·ha⁻¹ of PTs produced optimal results, increasing the LAP yield by 12.82% and the soil quality by 76.51%, while improving the ESP soil quality by 46.21%. The higher yield was mainly attributed to a significant increase in the soil pH (0.72–1.58 units) and enhanced chemical and biological properties (higher exchangeable calcium (ExCa), exchangeable magnesium (ExMg), the total exchangeable salt base ion (TEB), and catalase (CAT) and urease (UE) content and lower soil exchangeable acidity (EA), exchangeable hydrogen ion (ExH), and exchangeable aluminum (ExAl) levels). Notably, a synchronized increase in the total phosphorus (TP) and total potassium (TK) during LAP cultivation, combined with simultaneous growth of TP, available nitrogen (AN), and available phosphorus (AP) during ESP cultivation, and a significant increase in TP and AP during SM cultivation, effectively promoted crop yield. Furthermore, continuous PT application significantly enriched phosphorus (P)-soluble functional bacteria, such as Actinomycetes and Chloroflexota, and enhanced the stability of bacterial-fungal cross-boundary networks. In summary, optimal acidity levels and favorable soil texture improved soil quality, consequently increasing corn and potato yields. This study reveals for the first time that PTs can substantially increase crop production via a synergistic mechanism involving acid-base balance, structural improvement, and microbial activation. Not only does this provide a novel strategy for rapidly improving acidic soils, but it also establishes a solid theoretical and technical foundation for utilizing PT resources. Full article

Arzanol, a prenylated phloroglucinol–α-pyrone heterodimer, displays a broad range of pharmacological properties. This review compiles findings from 2007 to 2025 on its chemistry, conformational behavior, bioactivities, molecular targets, and pharmacokinetics. Arzanol shows potent anti-inflammatory activity through NF-κB inhibition and dual suppression of mPGES-1 and 5-LOX, antioxidant and cytoprotective effects via radical scavenging and metal chelation, and selective antibacterial activity. Arzanol also modulates autophagy, mitochondrial function, and metabolic pathways, with high-affinity binding to brain glycogen phosphorylase and SIRT1. Pharmacokinetic data indicate gastrointestinal stability, intestinal absorption, and limited blood–brain barrier penetration. In vivo, arzanol exhibits neuroprotective, neurobehavioral, and metabolic effects, while showing selective cytotoxicity toward cancer cells with minimal impact on normal cells. This review evaluates the diverse biological activities of arzanol, analyzing the relationship between its unique conformational flexibility and multitarget pharmacological effects. Full article

Matricaria chamomilla and Tripleurospermum inodorum (syn. Matricaria inodora) are two closely related species in the Asteraceae family that are often mistaken for one another due to their similar appearance. However, they differ significantly in their chemical composition and biological activities. This study offers comparative characterisation through microscopy, phytochemical profiling, and biological assays. Microscopic observations revealed distinct morphological differences in the structure of the receptacle and the size of the pollen grains between the two species. Total phenol and flavonoid contents were quantified using spectrophotometry, while essential oils were extracted through hydrodistillation and analysed by gas chromatography–mass spectrometry (GC-MS). M. chamomilla was found to have a higher phenol content (20.48 mg GAE/g DW), whereas T. inodorum showed a greater flavonoid concentration (15.93 mg RE/g DW). The essential oils from each species displayed different chemical composition: M. chamomilla was dominated by bisabolol oxides and chamazulene, while T. inodorum primarily contained β-farnesene and cis-lachnophyllum ester. The antioxidant activity of both species was evaluated using the DPPH assay and found to be moderate compared to standard antioxidants, such as ascorbic acid (IC₅₀ < 5 µg/mL). The IC₅₀ values for M. chamomilla ranged from 17.7 to 21.5 µg/mL, while for T. inodorum, they ranged from 8.4 to 10.2 µg/mL. In antimicrobial tests, the essential oil of T. inodorum inhibited both Staphylococcus aureus and Candida albicans, while M. chamomilla was only active against C. albicans. These findings highlight important morphological and chemical markers that differentiate the two species and affirm T. inodorum as a promising source of bioactive compounds. Full article