Search Results (2,812)

Background/Objectives: Stem cells with the ability to differentiate into other cell types and self-renewal afford a powerful apparatus for the healthcare system to replace and rejuvenate damaged tissues and organs in the treatment of various diseases. For the last few decades, stem cell therapy (SCT) has evolved from being an experimental approach to a recognized clinical treatment. SCT and regenerative medicine have garnered tremendous attention and become prominent tools, especially in treating chronic and acute disease and addressing organ failures, and in their repair and replacement, which are directly associated with human health, life, and longevity. Methods: In this review, after providing a brief history and need for the SCT, the employed delivery techniques utilizing various biomaterials, as well as recent developments in nanotechnological methods, are presented. It is focused on the current literature for the recent progress of stem cell therapy and tissue engineering for the application fields in neurological, ophthalmological, cardiovascular, orthopedic, and oncology, followed by the challenges associated with their applications. Results: In addition to safety concerns, challenges such as uncontrollable differentiations, genetic and epigenetic instability, limited cell survival and integration, immunological rejections, scaling and manufacturing drawbacks, as well as unpredictable behaviors and clinical limitations were reviewed. Conclusions: Future aspects with respect to regenerative medicine and tissue engineering, gene editing and personalized therapies, immunomodulation and anti-inflammatory applications, as well as neuroregeneration and treatment of neurodegenerative disorders are reflected. Full article

Sodium hypochlorite (NaOCl) remains the gold standard irrigant in endodontics due to its proteolytic and antimicrobial properties, whereas hydrogen peroxide (HP) is widely used for internal bleaching because of its oxidative capacity. Both agents have been associated with chemical and structural alterations in dentin; however, the impact of their sequential application on the organic–mineral balance has not been fully elucidated. Objective: To evaluate whether the isolated and sequential application of 5.25% NaOCl and 37.5% HP induces chemical alterations in dentin by analyzing changes in the organic matrix and mineral phase using Fourier-transform infrared spectroscopy (FTIR) and Energy-dispersive X-ray spectroscopy (EDX). Methods: Twenty-four independent dentin sections (n = 6 per group) from six human third molars were distributed using a tooth-balanced allocation into four groups: Control, NaOCl (5.25%, 15 min), HP (37.5%, 30 min), and sequential NaOCl+HP. FTIR assessed organic (amide I, II, III, CH₂) and inorganic (phosphate, carbonate) components through baseline-corrected integrated areas, Full Width at Half Maximum (FWHM), and molecular ratios. Surface elemental composition and the calculated Ca/P atomic ratio were determined by EDX. Multiple sub-measurements per specimen were averaged before statistical analysis. Data were analyzed using Kruskal–Wallis and Mann–Whitney U tests with Bonferroni correction (p < 0.05). Results: FTIR revealed treatment-dependent modifications. NaOCl reduced absorbance in organic-associated bands, indicating collagen degradation, whereas HP altered the mineral phase. The NaOCl+HP group exhibited increased numerical values for integrated band areas, with differences detected in carbonate, phosphate, and amide III bands (p < 0.05), reflecting structural disorganization and modified spectral signal rather than tissue preservation. No differences were detected across the calculated infrared ratios (p > 0.05). EDX showed decreased absolute atomic percentages of Ca, P, and O in the NaOCl+HP group (p < 0.05), indicating structural demineralization, while its stoichiometric Ca/P ratio remained at 1.56. Isolated HP shifted the mineral stoichiometry to the highest numerical Ca/P ratio (1.69; range 1.58–1.80). Fluorine decreased across all treated groups (p < 0.001). Conclusions: Sequential NaOCl and HP application triggers distinct chemical alterations compared to individual treatments, inducing severe structural disorganization of the organic network and absolute mineral depletion of Ca and P. This multi-agent sequence alters dentin stoichiometry, which may compromise the biomechanical integrity of the tissue. Full article

Cardamine hupingshanensis (C. hupingshanensis) is an important dietary source of selenium for humans due to its remarkable capacity for selenium hyperaccumulation. As core components of the SCF (SKP1–Cullin–F-box) ubiquitin ligase complex, F-box proteins play vital roles in plant responses to environmental stress, such as salt and drought. However, information regarding the F-box gene family in C. hupingshanensis and its potential functions in regulating responses to abiotic stress remains limited. In this study, members of the F-box gene family in C. hupingshanensis were identified through sequence alignment. Comprehensive bioinformatic analyses, including analyses of physicochemical properties, phylogenetic relationships, subcellular localization, conserved motifs and domains, gene structure, chromosomal distribution, promoter cis-elements, and gene duplication events, were performed using TBtools and associated online resources. In particular, a total of 548 F-box genes were identified and classified into nine distinct groups based on phylogenetic analysis. Protein sequence analysis predicted 15 conserved motifs and 18 distinct domains across the identified F-box proteins. Promoter analysis suggested the presence of 32 different cis-elements that may be potentially associated with growth, development, hormone signaling, and abiotic stress responses. Furthermore, 283 collinear gene pairs were detected within the C. hupingshanensis genome, providing insights into the possible expansion of this gene family. Quantitative real-time PCR was employed to examine the tissue-specific expression levels of F-box genes in various organs, as well as their expression profiles in response to exogenous selenium, salt, osmotic stress, and abscisic acid treatment. The results indicated that 11 ChFBX genes responded to exogenous selenium, salt, osmotic stress, or abscisic acid. Notably, transgenic plants overexpressing ChFBX171 displayed heightened sensitivity to salt stress during seed germination. In conclusion, this study provides a comprehensive identification and characterization of 548 F-box genes in C. hupingshanensis and offers valuable insights into the potential role of ChFBX genes, particularly ChFBX171, in mediating responses to abiotic stress. Full article

Ex vivo liver perfusion (EVLP) sustains human or large animal livers outside the body under near-physiological conditions, enabling functional monitoring for lactate clearance, bile production, and oxygen consumption and allowing targeted therapeutic interventions. Originally developed to optimize donor grafts for transplantation, EVLP has evolved into a powerful translational research platform bridging preclinical discovery and early clinical translation. This review discusses EVLP as a platform for gene therapy, immunotherapy, pharmacology, and personalized medicine, with particular emphasis on gene- and immune-based interventions as mechanistically mature exemplars. We consolidate advances in pharmacological testing and toxicity modeling, viral and non-viral gene delivery, genome engineering, and immunomodulation using perfused livers. We further describe emerging applications, including autologous EVLP pathways for organ-confined therapy, ex vivo liver surgery, and bioengineering strategies such as biliary organoid repair, RNA interference, and mitochondrial transfer. We highlight how these applications align with a paradigm shift in biomedical research, including the NIH’s recent initiative to prioritize human-based experimental models over animal-only studies. By leveraging transplant-declined or surgically resected organs that would otherwise be unused, ex vivo perfusion bridges the gap between pre-clinical testing and clinical practice, enabling real-time evaluation of interventions in functional human tissue. We discuss both the scientific opportunities afforded by EVLP and the technical, biosafety, and ethical challenges that must be addressed to enable responsible clinical translation. Full article

The plastic pieces of synthetic polymers, which were previously regarded as primary pollutants of the environment, are increasingly being discovered as internal pollutants of the human body. This review provides a comprehensive overview of the available evidence on human exposure, tissue distribution, and associated biological effects of micro- and nanoplastics. Ingesting contaminated food and water is the major exposure pathway, with inhalation and dermal contact being secondary routes. Various organ systems have been identified as containing polymer particles through the use of advanced analytical methods, including blood, liver, lungs, placenta, breast milk, and brain tissue. Experimental animal studies suggest associations with tissue injury, metabolic illness, and neurotoxicity. Polyethylene, polypropylene, polystyrene, and polyethylene terephthalate are the most frequently found polymers in human samples. New clinical findings indicate potential health implications, though current human evidence remains largely associative rather than causal: a cardiovascular study observed more than a two-fold rise in mortality among patients with polymer-containing arterial plaques, and recent evidence demonstrates over-accumulation of polymers in brain tissue, raising questions about neuroinflammatory processes. Detection technologies have advanced substantially, with deep learning-based polymer classification achieving 95–99% accuracy and ultrasensitive electrochemical and surface plasmon resonance biosensors reaching detection limits approaching 10⁻¹¹ M. Despite these advances, critical issues remain, including lack of standardized analytical procedures, absence of chronic exposure models for humans, and insufficient longitudinal epidemiological data. To address these gaps, physiologically relevant experimental systems including organoids and organ-on-chip platforms will be required, in addition to well-designed prospective cohort studies. Full article

Three-dimensional (3D) endothelium–stromal co-cultures were established using human endometrial cells from biopsy of healthy women (n = 13) and serum samples from both healthy and endometriotic women (n = 5). For 3D construction, stromal cells were mixed with extracellular matrix components, followed by endothelial cell seeding. Morphological analysis confirmed the organization of tissue-like structures. Immunofluorescence and flow cytometry verified the expression of specific stromal and endothelial markers (Cytokeratin, Vimentin, Insulin-like growth factor-binding protein 1, and von Willebrand factor). Cell viability and proliferation increased over time, with minimal cell death. To test functional responsiveness, these co-cultures were exposed to inflammatory serum from endometriotic patients. After 48 h, cytometric bead array showed elevated levels of IL-1β, IL-6, and IL-8 in cultures treated with inflammatory serum, indicating preserved functional activity and responsiveness. By allowing detailed investigation of functional endometrial states within a physiologically relevant cellular network, this approach provides a valuable organoid-like tool to explore conditions such as implantation failure and infertility and to study the cellular interactions underlying reproductive pathologies. Full article

Polycyclic aromatic hydrocarbons (PAHs) are widespread, persistent pollutants that can be sequestered within human adipose tissue due to their lipophilic nature. While this accumulation poses toxicological risks depending on dose and individual susceptibility, the specific morphological impact of chronic PAH storage on tissue architecture remains poorly defined. Here, we performed a histopathological and morphometric analysis on human subcutaneous adipose tissue samples characterized by high pyrene levels. We evaluated tissue organization, collagen distribution, the presence of inflammatory, neural, and vascular alterations and adipocyte morphometry to assess the structural response to PAH sequestration. Despite high pyrene concentrations, PAH-positive tissues maintained preserved overall architecture with normal collagen distribution, absence of lymphocytic infiltration, low macrophages, unaltered nerve fiber patterns, without evidence of vascular remodeling. Morphometry revealed smaller adipocyte area in PAH-positive samples, although not statistically significant. Our experimental data indicate that high PAH accumulation does not necessarily induce subcutaneous adipose tissue remodeling, suggesting that biochemical or metabolic alterations might occur even in the absence of evident histological changes. Further studies, with a broadened cohort, are needed to define the threshold at which PAHs’ presence translates into permanent tissue damage. Full article

Plant growth-promoting rhizobacteria (PGPR) foster sustainable and environmentally friendly agriculture by promoting plant growth and development. PGPR colonize the root rhizosphere, rhizoplane and root tissues, where they drive organic matter turnover and nutrient cycling, thereby increasing the (phyto)availability of essential macro- (P, N, K, S, Ca, Mg) and micronutrients (Fe, Zn, Mn, Mo, Co, Ni, Cu, B). This process relies on various mechanisms, including acid secretion (rhizospheric acidification and metal chelation), siderophore production (binding Fe, Zn, and other metals) and hydrolytic enzyme-mediated catalysis (phosphatases, phytases). Some of these microorganisms can also modulate the phytohormonal balance, reshaping root architecture and enhancing nutrient uptake, and even can alleviate abiotic stress or serve as biocontrol agents, contributing to pathogen resistance. Even though plant cultivation practices relying solely on synthetic fertilizers rapidly increase crop yield and productivity, they eventually result in crops poor in essential micronutrients and trace elements. This may contribute to micronutrient malnutrition in the human population. On the contrary, PGPR enhance both crop yield and nutritional quality. Therefore, in utilization with other nutrient sources, PGPR provide a promising and scalable approach towards advancing environmentally sustainable agriculture systems. Full article

D-box binding protein (DBP) is a high-amplitude proline- and acidic amino acid-rich basic leucine zipper (PAR bZIP) transcription factor that functions as a key circadian output regulator downstream of the core molecular clock. Although DBP is widely recognized as a clock-controlled gene, its broader role in converting circadian timing into tissue-specific physiological programs remains incompletely integrated. In this review, we synthesize current evidence supporting DBP as a context-dependent D-box-centered regulatory node. We first summarize the upstream mechanisms that establish rhythmic Dbp expression, including CLOCK–BMAL1-dependent transcription, promoter-level amplification, signaling-dependent modulation, and post-translational control of DBP stability. We then discuss how DBP, together with related PAR bZIP activators and the opposing repressor E4 promoter-binding protein 4/nuclear factor interleukin 3 regulated (E4BP4/NFIL3), regulates D-box-mediated transcriptional output. Finally, we examine tissue-selective DBP functions in hepatic metabolism, pancreatic β-cell secretory competence, neural and behavioral regulation, reproductive neuroendocrine timing, and T helper 9 (Th9)-associated antitumor immunity. Across these systems, DBP does not act as a universal circadian effector; rather, its function depends on chromatin accessibility, cofactor availability, competing transcription factors, and local signaling context. We also highlight the current limits of human translational evidence and propose that DBP-centered signatures may be useful for interpreting circadian output failure in disease. Overall, DBP provides a mechanistically informative framework for understanding how circadian time is transformed into organ-specific physiological function and pathological vulnerability. Full article

Background/Objectives: Chlamydia trachomatis (CT) is a prevalent sexually transmitted pathogen associated with pelvic inflammatory disease, infertility, and has been proposed as a potential contributor to carcinogenesis through chronic inflammation and tissue remodeling. The molecular mechanisms triggered by CT infection in fallopian tube cellular contexts and their relevance to ovarian cancer transcriptomes remain incompletely understood. Methods: We analyzed GSE109428, profiling primary human fallopian tube mesenchymal cells infected with CT, to identify differentially expressed genes and characterize affected pathways using g:Profiler and STRING protein–protein association networks (confidence ≥ 0.7). To provide translational context, we computed ssGSEA scores in TCGA-OV for four signatures capturing IFN/ISG, TNF/NF-κB, NOD/innate immunity, and ECM programs, and evaluated inter-signature correlations and exploratory associations with overall survival (OS) and progression-free interval (PFI). Results: CT infection induced sustained inflammatory and interferon-associated transcriptional programs, with STRING networks highlighting cytokine hubs and a densely connected ISG module. Genes downregulated at 48 h post-infection (48-hpi) showed coherent enrichment for ECM organization and adhesion pathways. In TCGA-OV (n = 307), inflammatory and innate immune signatures co-occurred across tumors, with moderate correlations between TNF/NF-κB and NOD/innate (ρ = 0.591) and IFN/ISG and NOD/innate (ρ = 0.534). Exploratory survival analyses showed no significant associations with OS or PFI in Kaplan–Meier analyses or multivariable Cox models, including clinically adjusted and tumor microenvironment-adjusted specifications. Conclusions: CT infection induces sustained inflammatory and interferon-linked programs and coordinated repression of ECM networks in fallopian tube mesenchymal cells. Analogous immune transcriptional states co-occur in ovarian tumors, though the signatures evaluated did not yield robust prognostic signals in TCGA-OV. As this is an entirely in silico study without experimental validation, these findings should be treated as hypothesis-generating; thus, further mechanistic and experimental studies are warranted to clarify how CT infection-associated pathways may intersect with female tumorigenesis. Full article

The sustainability, crop production, and food safety of agriculture are increasingly challenged by microplastic pollution, as agricultural soils are the largest reservoirs and may serve as points of contact for plastic particles in the food chain. This review provides a comprehensive overview of plant materials, fate and uptake pathways, detection techniques, and the possible risks of microplastics in agriculture. Agroecosystems are also a source of microplastics, such as plastic mulch films, sewage sludge, compost and manure additives, wastewater irrigation, polymer-coated fertilizers, greenhouse materials, atmospheric deposition, and decomposition of discarded agricultural plastics. Their distribution and mobility in soil are controlled by polymer composition, particle size, morphology, density, surface ageing, soil texture, organic matter content, tillage practices, runoff, leaching, and soil biota. Recent data show that microplastics, especially smaller microplastics and nanoplastics, can attach to root surfaces, penetrate plants via cracks in roots, areas of lateral root development, and apoplastic pathways, and eventually move to tissues aboveground. Plant tissue detection is often accomplished by digestion of the sample, density separation, visual and fluorescence microscopy, Fourier-transform infrared spectroscopy, Raman spectroscopy, pyrolysis–gas chromatography mass spectrometry, and electron microscopy, but standardization of these methods remains a significant challenge. Microplastics can disrupt seed germination, root structure, nutrient absorption, photosynthesis, oxidative homeostasis, biomass buildup, yield development, and quality. Further, their capacity to transport additives, plasticizers, heavy metals, and persistent organic pollutants raises concerns about the transfer of contaminants to edible plant parts and their potential transfer to human diets. Further studies are needed focusing on field-realistic exposure conditions, long-term crop–soil interactions, nanoplastics behaviour, standardised analysis procedures, uptake and translocation pathways, edible crop risk assessments, and sustainable mitigation approaches to reduce microplastics in agroecosystems. Full article

Carbonyl stress, chronic inflammation, and progressive tissue injury accompany type 2 diabetes mellitus (T2DM) and obesity. Yet, the molecular systems that connect these processes with cardiac, vascular and neuronal complications are incompletely defined. This review examines the AGE–RAGE–DIAPH1 axis as a mechanistic link between metabolic dysfunction and diabetic myocardial and neuronal injury, with emphasis on vascular and myocardial remodeling and emerging implications for autonomic neuronal vulnerability. We summarize current evidence on the formation and accumulation of advanced glycation end-products and other RAGE ligands in metabolic disease, DIAPH1’s structural and signaling role as an intracellular effector of RAGE, and the cellular consequences of pathway activation in vascular, neural, and cardiac tissues. Across experimental models, this signaling axis promotes oxidative stress and inflammatory activation, leading to endothelial dysfunction and barrier failure. Subsequent fibrotic remodeling provides a biologically plausible route through which metabolic stress may be translated into persistent organ injury. In the heart, these mechanisms are linked to coronary microvascular dysfunction, altered cardiomyocyte phenotype, calcium handling abnormalities, and myocardial fibrosis. In the autonomic nervous system, limited but emerging data connect RAGE activation to oxidative injury and mitochondrial dysfunction, abnormal neuronal excitability, and structural vulnerability. Direct evidence linking DIAPH1 to autonomic neurons is lacking. We also review biomarker candidates related to this pathway, including circulating AGEs and soluble RAGE isoforms, skin AGE measurements, imaging markers of myocardial remodeling, and autonomic functional measures. Finally, we discuss pharmacological and natural compounds that target AGE formation, ligand accumulation, RAGE signaling, or intracellular protein interactions linked to this axis. Overall, the available evidence supports the AGE–RAGE–DIAPH1 axis as a credible mechanistic concept and a potentially informative translational hypothesis in T2DM. However, the AGE–RAGE component is supported more strongly than DIAPH1-specific involvement in human diabetic myocardial disorder or cardiovascular autonomic neuropathy. The value of DIAPH1 as a biomarker or therapeutic target in these neurocardiac complications remains to be established. Full article

Elabela (ELA/APELA/Toddler) is an endogenous peptide ligand of the apelin receptor APLNR (also known as APJ) and, together with apelin, forms the apelinergic signalling system. Its role in embryonic development, the cardiovascular system, the kidneys and the endothelium is becoming increasingly well characterised, whilst its function in metabolic regulation remains unresolved. Elabela activates pathways essential for metabolic homeostasis—PI3K/Akt, AMPK-related pathways, redox regulation, inflammatory control and pro-survival cascades—but no study has shown that it directly regulates adipocyte lipid metabolism. This narrative review categorises the evidence at the receptor, organ, immunometabolic and intra-adipocyte levels, and also considers the adipose tissue microenvironment as a distinct level of potential relevance. The available data support a role for Elabela as a candidate mediator of lipid-related metabolic dysfunction—via anti-inflammatory, antioxidant and tissue-protective mechanisms—with macrophage lipid metabolism representing the most informative immunometabolic interface. Human studies remain scarce, heterogeneous and limited by a lack of standardisation in assay methods and the unresolved specificity of isoforms. Elabela should therefore be regarded as a candidate indirect modulator of metabolic homeostasis and a candidate biomarker of cardiometabolic stress or adaptation—not as a confirmed direct regulator of adipocyte lipid metabolism. Full article

Three-dimensional (3D) cardiac models, including spheroids, organoids, and organ-on-chips, are advanced systems for studying human physiology, disease, and drug responses with greater biological relevance than 2D models. As their use expands in biomedical research, tissue engineering, and regenerative medicine, reliable preservation methods are needed. However, cryopreservation often fails to protect 3D systems due to limited cryoprotectant penetration, ice formation, and mechanical stress during freezing and thawing. Room-temperature (RT) preservation has emerged as a promising alternative for short-term transport. This study evaluated a RT-based transport medium (CellShip^®) for preserving cardiac organoids for up to seven days, compared with conventional cryopreservation using slow-freezing in Cryostor^®CS10. Viability and functionality were assessed using apoptosis, ATP levels, beating activity, proliferation, and size. During maturation, organoids showed increased size, ATP levels, and beating capacity. Cryopreservation reduced size, proliferation, ATP levels, and altered beating, while increasing apoptosis. In contrast, RT preservation maintained stable viability and functionality after recovery. These findings demonstrate that RT preservation effectively maintains cardiac organoid integrity and function, offering a promising alternative for short-term storage and transport, with potential terrestrial and nonterrestrial applications. Full article

Human ageing and longevity are increasingly understood as biologically integrated and heterogeneous processes shaped by interactions among genetic susceptibility, epigenetic remodelling, and environmental modulation. This narrative review examines these interconnections within a nutrigenomic framework, with particular emphasis on how inherited variation and epigenetic plasticity may influence responses to ageing-related interventions. A structured literature search was conducted in PubMed, Scopus, Web of Science, and Embase, focusing on English-language studies published during the last 10 years. The review was organized into three major domains: (i) genetic determinants of longevity, (ii) epigenetic mechanisms of ageing, and (iii) intervention-responsive pathways relevant to precision geroscience. Current evidence supports a polygenic model of longevity in which loci such as FOXO3 and APOE show the most consistent human associations, while telomere maintenance, insulin/IGF-1 and mTOR signalling, sirtuins, Klotho, inflammatory mediators, and DNA repair remain biologically important but variably supported at the variant level. Epigenetic mechanisms, including DNA methylation drift, epigenetic clocks, histone modifications, chromatin remodelling, heterochromatin loss, and non-coding RNA regulation, provide an environmentally responsive interface linking genetic background to ageing phenotypes. Nutritional, pharmacological, behavioural, and circadian interventions converge on overlapping molecular pathways involving AMPK, mTOR, FOXO, sirtuins, autophagy, mitochondrial maintenance, and inflammatory signalling, although human evidence remains heterogeneous and biomarker modulation should not be equated with clinically meaningful slowing of organismal ageing. Overall, this review highlights the value of integrating genetics, epigenetics, and intervention biology to support a more cautious and translationally relevant model of healthy ageing. It also underscores the need for precision nutrigeroscience approaches that account for tissue context, baseline physiology, and inter-individual molecular variability. Full article