Search Results (3,790)

Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality, with poor survival outcomes despite advances in surgery, chemotherapy, targeted therapy, and immunotherapy. The tumor microenvironment (TME) plays a central role in sustaining tumor growth, immune evasion, and systemic metabolic dysfunction. In this study, we performed an integrative analysis of differentially expressed microRNAs (miRNAs) to uncover their contributions to dysregulated signaling networks in NSCLC. hsa-miR-486-5p was identified as a prominent differentially expressed candidate miRNA. Using mathematical modeling and regression-based reduction, we identified Forkhead Box O1 (FOXO1) and Unc-51 like Autophagy Activating Kinase 2 (ULK2) as critical regulatory nodes that integrate oncogenic signaling with cellular homeostasis. Aberrant expression of hsa-miR-486-5p was found to modulate pathways including PI3K/AKT/mTOR, NF-κB, and JAK-STAT3, thereby promoting tumor progression and secretion of inflammatory cytokines. These cytokines, viz., IL-6, TNF-α, and IL-1β, activate muscle-specific protein degradation pathways through E3 ubiquitin ligases TRIM63 and FBXO32, linking NSCLC progression to cancer-associated sarcopenia. Quasipotential landscape analysis further revealed dynamic phenotypic transitions between stable and unstable states, highlighting the adaptability of tumor–host interactions. Collectively, our findings demonstrate that miRNA-mediated regulatory networks not only drive NSCLC progression and inflammation but also contribute to systemic muscle wasting. These insights emphasize the need for novel therapeutic strategies, including RNA-based interventions, to overcome resistance, improve survival, and address the metabolic complications associated with NSCLC. Full article

Breast cancer remains a leading cause of cancer-related mortality worldwide, with epigenetic mechanisms like N⁶ methyladenosine (m⁶A) modification playing a crucial role in tumorigenesis. The interaction between microRNAs and m⁶A regulators, such as the methyltransferase METTL14, is increasingly recognized as a key pathway in oncogenesis. This study investigated whether miR-30c-2-3p regulates METTL14 expression to influence global m⁶A levels and cell migration in breast epithelial (MCF12A) and breast cancer (MCF7) cell lines. Following transfection with miR-30c-2-3p mimics, successful overexpression was confirmed in both cell lines. Subsequent RT-qPCR and Western blotting analyses demonstrated that METTL14 mRNA and protein levels were significantly reduced at 24 and 48 h post-transfection (p < 0.05). Concurrently, global m⁶A RNA methylation levels decreased, with a more pronounced reduction observed in MCF12A cells (p < 0.001). Functionally, wound healing assays revealed that miR-30c-2-3p significantly inhibited migration, reducing wound closure by 30–44% in MCF7 cells and by 66–72% in MCF12A cells. These findings reveal a novel regulatory axis involving miR-30c-2-3p, METTL14, and m⁶A, suggesting that miR-30c-2-3p functions as a tumor suppressor and represents a promising biomarker and therapeutic target in breast cancer. Full article

Pregabalin (PGB) exerts its therapeutic effects by binding to the α₂δ auxiliary subunits of voltage-gated calcium channels and modulates synaptic transmission in the brain. However, its influence on cerebellar parallel fiber–Purkinje cell (PF–PC) synaptic transmission remains unclear. In the present study, we investigated the effects of PGB on PF–PC synaptic transmission using whole-cell patch-clamp recording, glutamate fluorescence imaging, immunohistochemistry, co-immunoprecipitation, Western blotting, and pharmacological approaches. Micro-application of PGB to the cerebellar molecular layer induced a concentration-dependent inhibition of PF–PC excitatory postsynaptic currents (EPSCs), accompanied by an increased paired-pulse ratio. The inhibitory effect of PGB on PF–PC EPSCs was abolished by extracellular blockade of N-methyl-D-aspartate receptors (NMDAR) or their GluN2A subtype, as well as by disruption of α₂δ-1–NMDAR complexes, but not by intracellular NMDAR inhibition. Glutamate sensor imaging further showed that PGB markedly reduced the fluorescence intensity of glutamate release evoked by PF stimulation. In the presence of tetrodotoxin (TTX) and a gamma-aminobutyric acid type A (GABAA) receptor antagonist, PGB reduced the frequency of miniature excitatory postsynaptic currents (mEPSCs) without affecting their amplitude. The PGB-induced reduction in mEPSC frequency was fully abolished by extracellular blockade of GluN2A-containing NMDARs or disruption of α₂δ-1–NMDAR complexes. Similarly, the inhibitory effects of PGB on PF–PC EPSCs and mEPSCs were eliminated by extracellular PKA inhibition, but not by intracellular protein kinase A (PKA) inhibition. Western blot analysis showed that PGB significantly increased PKA phosphorylation in the molecular layer of the cerebellar cortex. Immunoreactivity for GluN2A and α₂δ-1 subunits was colocalized within the molecular layer and abundantly distributed around the dendrites and somata of PCs. Co-immunoprecipitation further verified that α₂δ-1 was co-precipitated with GluN1 in cerebellar molecular layer tissue samples. The results indicate that PGB depresses glutamate release from parallel-fiber terminals in the mouse cerebellar cortex through the presynaptic α₂δ-1-coupled GluN2A-containing NMDAR/PKA signaling pathway, thereby attenuating PF–PC synaptic transmission. Full article

Exosomes are a kind of nanoscale extracellular vesicle secreted by almost all cell types and considered promising biomarkers for disease diagnosis since they could carry abundant proteins, nucleic acids, and lipids that reflect parental cell states. However, conventional exosome detection methods suffer from several limitations including insufficient specificity, low throughput, high costs, and inadequate sensitivity for clinical applications. By contrast, field-effect transistor (FET) biosensors are a promising alternative by enabling label-free, real-time, and ultrasensitive detection of exosomes through direct transduction of biorecognition events into electrical signals. This review first introduces the fundamental principles and device structure of FET biosensors, as well as exosome isolation strategies. The recent advances in exosome analysis using FET-based biosensors are then presented, which are categorized into two primary strategies: (1) direct detection of intact exosomes based on surface markers, including tetraspanin proteins (CD9, CD63, CD81, etc.) and disease-specific biomarkers, and (2) detection of exosomal contents including microRNA and protein biomarkers following exosome lysis. Finally, we discuss current challenges of FET-based exosome detection and provide perspectives on future developments. Full article

Coronary artery bypass grafting (CABG) using the autologous saphenous vein (SV) remains widely performed for obstructive atherosclerosis; however, vein graft disease drives recurrent ischaemia through early thrombosis and progressive intimal hyperplasia, and accelerated atherosclerosis developing within the grafts. Extracellular vesicles (EVs) are membrane-bound particles that transfer proteins, lipids, and microRNAs between cells. They modulate endothelial dysfunction, vascular smooth muscle cell phenotypic switching, inflammation, and coagulation, which are core processes in vein graft remodelling. Arterialisation exposes the vein to abrupt rises in shear stress, cyclic stretch, and intraluminal pressure. These forces increase EV release and reshape EV cargo in experimental systems, suggesting a potential mechanism for amplifying early graft injury which warrants direct investigation in vein tissue. This review synthesises current evidence for cell-specific EV contributions from ECs, vascular smooth muscle cells, platelets, and macrophages, and appraises EV-associated microRNAs with biomarker potential relevant to graft failure pathways. We also review therapeutic strategies that may modulate EV signalling including antiplatelet therapy, statins, KCa3.1 inhibition, and pro-reparative mesenchymal stromal cell-derived EVs. No published clinical studies evaluate EV-based biomarkers specifically for saphenous vein graft patency, and none prospectively predict saphenous graft failure. CABG provides a well-defined time zero event that enables longitudinal sampling and risk stratification. Prospective studies linking EV phenotypes and miRNA signatures to imaging-defined graft outcomes are needed to support clinical translation. Full article

Background: Postmenopausal osteoporosis is associated with cellular senescence and the accumulation of the senescence-associated secretory phenotype (SASP). While mesenchymal stem cell (MSC)-derived exosomes show tissue repair potential, the efficacy and mechanisms of MSC-derived apoptotic vesicles (apoVs) remain unclear. This study compared MSC-apoVs and exosomes in postmenopausal osteoporosis and investigated the underlying epigenetic mechanisms. Methods: Therapeutic efficacy was evaluated in an ovariectomized (OVX) mouse model and senescent human bone marrow mesenchymal stem cells (hBMMSCs). Small RNA sequencing identified differential microRNA (miRNA) cargos between vesicle types. SASP-related cytokine expression (IL-6, TNF-α, MCP-1) and pathway activation were assessed by RT-qPCR, ELISA, and Western blot. Results: MSC-apoV treatment attenuated bone loss in OVX mice and reduced SASP expression in senescent hBMMSCs to a greater extent than exosomes. Small RNA sequencing revealed that apoVs were enriched with a specific miRNA cluster, including hsa-let-7b-5p, hsa-miR-92a-3p, and hsa-miR-98-5p. Bioinformatic analyses identified BRAF and CRKL as downstream targets of this miRNA cluster, supported by reduced protein levels after apoV treatment. Subsequent molecular assays showed that apoV treatment inhibited the phosphorylation of both the MAPK (p38 and JNK) and NF-κB (p65) signaling pathways, which correlated with reduced local inflammation in the bone marrow microenvironment and preserved osteogenic differentiation capacity. Conclusions: MSC-apoVs attenuate postmenopausal osteoporosis more effectively than exosomes. This enhanced efficacy is associated with the delivery of an enriched miRNA cluster that inhibits MAPK and NF-κB signaling, together with suppression of BRAF and CRKL protein expression. ApoVs may represent a cell-free therapeutic strategy for age-related bone loss. Full article

The tumor microenvironment (TME) is a highly adaptive and heterogeneous niche in which cancer stem cells (CSCs) promote immune evasion, metastatic dissemination, and therapy resistance. Among the mechanisms that support this phenotype, mitochondrial hijacking has emerged as a central strategy through which CSCs reprogram immune and stromal cells to favor tumor progression. This review synthesizes current evidence on how CSCs exploit mitochondrial transfer, particularly via tunneling nanotubes (TNTs) and extracellular vesicles (EVs), to impair antitumor immunity and remodel the metastatic niche. CSCs display marked metabolic plasticity, shifting between glycolysis and oxidative phosphorylation (OXPHOS) in response to environmental stress. They exploit this adaptability by transferring mitochondria and mitochondrial components to recipient cells, including tumor-associated macrophages (TAMs) and cytotoxic T cells, thereby disrupting ATP production, increasing oxidative stress, and skewing immune polarization. This mitochondrial hijacking contributes to an immunosuppressive milieu, stabilizes HIF-1α, and enhances PD-L1 expression, ultimately weakening T-cell activity and reinforcing CSC survival. EVs add another layer of regulation by transporting bioactive cargo, including oncogenic microRNAs (miRNAs) and mitomiRs such as miR-21, miR-210, and miR-34a. These molecules modulate mitochondrial gene expression, reshape immune signaling, and reinforce CSC phenotypes through autocrine and paracrine loops. Single-cell and spatial transcriptomic approaches have further revealed metabolic heterogeneity within CSC–immune synapses, identifying “metabolic hotspots” associated with profound immune dysfunction. Therapeutic strategies targeting OXPHOS, EV biogenesis, and miRNA activity are therefore being explored. In parallel, mitochondria-associated proteins such as TSGA10 may also contribute to CSC-driven immunometabolism regulation and deserve further investigation. Targeting downstream heterogeneity is like cutting the branches of a weed. Targeting the upstream mechanisms of mitochondrial hijacking and miRNA crosstalk aims to destroy the root (CSC plasticity) that generates the heterogeneity and drives therapy resistance in the first place. This review highlights mitochondrial hijacking and miRNA-mediated reprogramming as central determinants of CSC-driven immune escape and proposes a framework for precision interventions targeting CSC–immune interactions in metastatic cancer. Full article

Background/Objectives: Over the past two decades, non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression, reshaping the classical view of the genome as predominantly protein-coding. Among them, microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play central roles in controlling gene expression at multiple levels. Rather than acting independently, these molecules form complex and interconnected regulatory networks, and their interplay appears particularly relevant in cancer. This review aims to examine the mechanisms underlying miRNA-lncRNA cross-regulation and to explore their functional and clinical implications in tumor biology. Methods: We performed a comprehensive analysis of the current literature focusing on studies investigating miRNA-lncRNA interactions in cancer. Particular attention was given to mechanistic insights, including the competing endogenous RNA (ceRNA) hypothesis, as well as alternative regulatory models involving direct RNA interactions and chromatin-associated processes. Results: miRNA-lncRNA interactions have been associated with cancer progression and therapeutic response across different tumor types, although their mechanisms are highly context-dependent. While the ceRNA hypothesis, based on competition for shared microRNA response elements (MREs), provides a useful framework, it does not fully explain all observed phenomena. Evidence shows that miRNAs can directly regulate lncRNA stability, whereas lncRNAs can influence miRNA biogenesis. Additionally, chromatin-related mechanisms suggest that these interactions extend beyond post-transcriptional regulation. These RNA networks intersect with major oncogenic pathways, including PI3K/AKT/mTOR signaling, hypoxia responses, and epigenetic regulators such as EZH2, thereby affecting key cancer processes such as proliferation, epithelial–mesenchymal transition (EMT), and metabolic reprogramming. From a clinical perspective, the stability of ncRNAs in biological fluids highlights their potential as biomarkers. Combined miRNA-lncRNA signatures may improve diagnostic and prognostic accuracy compared to single markers, although further validation is required. Therapeutic strategies targeting ncRNA networks, such as miRNA mimics, antagomiRs, and lncRNA-directed approaches, are under investigation; however, challenges related to delivery, specificity, and toxicity remain. Conclusions: miRNA-lncRNA cross-regulation represents a complex and multifaceted layer of gene regulation in cancer. A deeper understanding of these interactions could support the development of more accurate diagnostic tools and more effective RNA-based therapeutic strategies, although significant technical and biological challenges still need to be addressed. Full article

Background/Objectives: Neuroblastoma is the most frequent solid tumor outside the brain in children and is associated with unfavorable outcomes in high-risk patients. Tannic acid, a naturally occurring polyphenolic compound, has been reported to exhibit anticancer activity; however, its molecular effects in neuroblastoma remain incompletely characterized. The present study aimed to evaluate the antiproliferative effects of tannic acid in SH-SY5Y neuroblastoma cells and to explore its potential associations with Toll-like receptor (TLR) signaling and selected microRNAs in an exploratory and correlative manner. Methods: Cell viability was assessed using the CCK-8 assay, which showed that tannic acid was associated with reduced cell proliferation in a dose- and time-dependent manner. Changes in the expression of TLR-related genes and selected microRNAs were analyzed by real-time PCR. TLR-4, NF-κB, and Caspase-3 protein concentrations were determined using ELISA assays. Results: Tannic acid treatment was associated with decreased expression of several TLR genes, with statistically significant reductions observed in TLR2, TLR4, and TLR7. Consistently, protein analyses indicated reduced NF-κB levels. MicroRNA analysis revealed a tendency toward increased expression of hsa-miR-146a-5p, whereas no significant changes were detected in other examined microRNAs. Conclusions: Overall, these findings suggest that tannic acid exhibits antiproliferative activity in SH-SY5Y cells and is associated with alterations in TLR-related gene expression and microRNA profiles. However, these observations are descriptive and correlative in nature and do not establish direct mechanistic relationships. Further in vivo and functional studies are required to validate these findings and to clarify their potential biological and therapeutic relevance. Full article

Micro- and nanoplastic (MNP) pollution has emerged as a global environmental and health concern, driving the rapid development of sensor technologies for faster, more sensitive, and field-deployable detection. This review synthesizes recent advances in optical, electrochemical, and biosensor platforms for MNP analysis and compares their analytical performance and practical feasibility. Optical sensors, including plasmonic, spectroscopic, and colorimetric systems, enable label-free and often rapid detection with material discrimination capability, and are well-suited for screening applications, though they commonly exhibit higher detection limits and matrix interference. Electrochemical sensors demonstrate the highest analytical sensitivity overall, frequently reaching low µg L⁻¹ to ng mL⁻¹ levels, with strong potential for miniaturization and on-site deployment; performance is further enhanced by nanostructured electrodes, photoelectrochemical designs, and signal amplification strategies. Biosensors incorporating peptides, aptamers, enzymes, or engineered proteins provide improved polymer selectivity and enable targeted detection, but face challenges related to stability, cross-reactivity, and reproducibility in complex samples. Practically, portable electrochemical and simple optical colorimetric platforms are currently the most feasible for field use, while hybrid bio-electrochemical systems show the highest performance potential. Future research should prioritize robust selective recognition elements, antifouling interfaces, standardized validation protocols, mixed-polymer quantification models, and integration with machine learning to enable reliable, real-world MNP monitoring. Full article

Yaks (Bos grunniens) on the Qinghai–Tibetan Plateau face severe nutritional limitations during the dry season due to dependence on highly lignified, low-quality roughage. Identifying safe and effective rumen regulators capable of enhancing fiber utilization in this species is therefore of great practical importance. This study employed a two-pronged approach integrating in vitro mechanistic investigation and in vivo validation to evaluate the effects of the amphoteric surfactant cocamidopropyl betaine (CAPB) on rumen fermentation, the micro-spatial distribution of digestive enzymes, apparent total tract digestibility, and the macroscopic growth performance of yaks. In the in vitro fermentation trial (Experiment 1), a randomized block design was employed where a straw-based high-forage diet was used as the substrate and supplemented with 0, 0.5, 1.0, 1.5, 2.0, 2.5, and 3.0% CAPB (based on substrate dry matter, DM) for a 48 h batch culture. The results showed that as the CAPB supplementation level increased, cumulative gas production, the degradation rates of DM and neutral detergent fiber (NDF), and the yields of total volatile fatty acids and microbial protein all exhibited significant quadratic responses (p < 0.05), peaking at the 0.5–1.0% supplementation levels. Concurrently, CAPB significantly promoted the transfer and release of carboxymethyl cellulase and xylanase into the free liquid phase (p < 0.01). In the in vivo validation trial (Experiment 2), 24 healthy growing male yaks (initial body weight 131.2 ± 8.4 kg) were allocated in a completely randomized design to four groups and fed a basal diet supplemented with 0, 0.5, 1.0, or 2.0% CAPB for 44 days. The results indicated that, while maintaining a stable DM intake, the addition of 0.5% CAPB significantly increased the average daily gain (ADG) of yaks (p < 0.05), improved the feed-to-gain ratio, and significantly enhanced the apparent total tract digestibility of NDF and ether extract (p < 0.05). However, when the supplementation dose exceeded the safety threshold (≥2.5% in vitro and ≥2.0% in vivo), both fermentation parameters and growth advantages declined. In conclusion, under the present experimental conditions, 0.5% CAPB improved roughage fermentation efficiency, putatively through an ‘enzyme elution’ mechanism, and was associated with macroscopic improvements in NDF and EE apparent digestibility and ADG in growing yaks. These findings identify 0.5% CAPB as a promising candidate rumen regulator for improving roughage utilization in growing yaks; broader generalization will require larger-scale and longer-duration trials. Full article

Consumer demand for sustainable solutions to protect against hair damage is growing, yet quantitative studies linking molecular interactions to mechanical strengthening and structural changes remain limited. Here, we investigated the effectiveness of biotechnologically obtained Saccharomyces Lysate as a formulated active ingredient for hair care. Molecular modeling was used to explore the interactions between peptides in the lysate and keratin and suggested a network of intermolecular interactions at multiple sites on the proteins. Based on these observations, the strength and structural integrity of hair fibers treated with Saccharomyces Lysate were assessed using tensile measurements. We observed an improvement in the strength of bleached hair tresses, with an increased Young’s modulus compared to tresses treated only with water along with a significantly increased break stress. To visualize the hair fibers and their surface roughness after treatment with the lysate, we employed micro-computed tomography (µ-CT) offering high-resolution visualization of hair fibers. We introduce this method to qualitatively highlight surface appearance following application of a cosmetic product and complemented it with combing force measurements. Our results demonstrate the potential of this complex mixture of small peptides to strengthen hair integrity and we propose a hypothesis for its putative mode of action at the molecular level. Full article

Tomato (Solanum lycopersicum L.) is a key source of bioactive compounds and essential minerals, but it also contains clinically relevant allergens. Despite growing concern about the effects of climate change on crop quality, the impact of heat stress during specific reproductive stages on fruit allergen accumulation remains poorly understood. This study aimed to investigate how the timing of heat stress affects tomato fruit quality, antioxidant traits, and the expression of major pan-allergens. Plants of the cultivar Micro-Tom were exposed to heat stress (40 °C for 8 h) at three flowering stages: pre-anthesis, anthesis, and post-anthesis. Ripe fruits were evaluated for morphological parameters, mineral composition, nutraceutical properties, antioxidant responses, and the expression of profilin and cyclophilin. Heat stress applied at post-anthesis significantly reduced fruit weight and diameter, while earlier treatments had limited morphological effects. Mineral composition was largely unchanged across treatments. In contrast, total phenolic content increased progressively with later stress application, whereas flavonoid content and antioxidant capacity (FRAP) remained relatively stable. Antioxidant enzyme activity showed only minor stage-dependent variation, suggesting a controlled oxidative response. Notably, allergen-related proteins exhibited distinct patterns: profilin accumulation increased progressively under heat stress, while cyclophilin showed a transient peak at anthesis. These findings demonstrate that the timing of reproductive heat stress differentially affects tomato fruit quality and allergen accumulation. This study provides novel insights into the stage-specific modulation of food allergens under heat stress, contributing to a better understanding of crop nutritional and allergenic properties in the context of climate change. Full article

Chromium (Cr) is one of the most toxic heavy metals in the environment. The tolerance to metal stress involves sophisticated regulation of gene expression networks, which involve microRNAs (miRNAs). However, the role of miRNAs in Cr stress response in Avicennia marina has not been resolved, and was addressed here. The analysis of response characteristics revealed that morpho-physiological traits such as root length, Cr accumulation level and antioxidant enzyme activity all exhibit significant changes under Cr stress. Via sRNA sequencing, a total of 27 known and 149 novel miRNAs were identified, 63 of which showed differential expression after Cr stress (q-value < 0.001). Further, 571 miRNA-target interaction pairs were identified for differentially expressed miRNAs, corresponding to 355 target genes. GO and KEGG analyses indicated that these target genes could participate in stress-related biological processes such as signal transduction, transcription regulation, protein synthesis and the MAPK signaling pathway. 54 miRNA target genes, corresponding to 37 miRNAs such as Ama-miR160, Ama-nmiR25-5p and Ama-nmiR118-5p, were enriched for “plant signal hormone transduction” (ko04075), “phenylpropanoid biosynthesis” (ko00940) and “MAPK signaling pathway” (ko04016), which indicated an important role of these miRNAs in regulating Cr stress response in A. marina. Based on the findings, a Cr stress-responsive regulatory model was developed, offering new insights into the molecular regulatory mechanisms of Cr response. In conclusion, this study shows the identity and potential role of miRNAs in the heavy metal stress response of A. marina, and provides the foundation for future research. Full article

This study aimed to examine the nutrient intake in Polish middle-distance runners. The secondary objective was to examine the biochemical profile and antioxidant status in the blood serum of the runners, and then compare to the control group. The research was conducted among 44 volunteers. Information regarding participants’ diet was gathered for three days before the study took place. Also, blood serum of athletes and control subjects was examined to obtain information about their antioxidant status, biochemical parameters, and micro- and macronutrients. This study showed that runners consumed more protein, sodium, zinc, phosphorus, water, vitamin A and E than the control group. The daily intake of selected vitamins, micro- and macronutrients in a group of athletes is approximately two times higher than in the control group. The control group consumed more polyphenols compared to the runners group (p < 0.05). The consumption of phenols was almost two times lower among runners compared to non-runners. The higher uric acid concentration (p = 0.025) and lower chloride concentration (p = 0.011) were observed in the blood serum of runners compared to the control group. The diet of middle-distance runners is well-balanced but need some modifications, especially regarding the intake of vitamin E, folates and polyphenols. Full article