Search Results (405)

Mesenchymal stem cells (MSCs), i.e., adult stem cells with immunomodulatory and secretory properties, contribute to tissue growth and regeneration, including healing processes. Some metal nanoparticles (NPs) are known to exhibit antimicrobial activity and may further potentiate tissue healing. We studied the effect of Ag, CuO, and ZnO NPs after in vitro exposure of mouse MSCs at the transcriptional level in order to reveal the potential toxicity as well as modulation of other processes that may modify the activity of MSCs. mRNA–miRNA interactions were further investigated to explore the epigenetic regulation of gene expression. All the tested NPs mediated immunomodulatory effects on MSCs, generation of extracellular vesicles, inhibition of osteogenesis, and enhancement of adipogenesis. Ag NPs exhibited the most pronounced response; they impacted the expression of the highest number of mRNAs, including those encoding interferon-γ-stimulated genes and genes involved in drug metabolism/cytochrome P450 activity, suggesting a response to the potential toxicity of Ag NPs (oxidative stress). Highly interacting MiR-126 was upregulated by all NPs, while downregulation of MiR-92a was observed after the ZnO NP treatment only, and both effects might be associated with the improvement of MSCs’ healing potency. Overall, our results demonstrate positive effects of NPs on MSCs, although increased oxidative stress caused by Ag NPs may limit the therapeutical potential of the combined MSC+NP treatment. Full article

More than 5.9 million plant germplasm accessions currently conserved in over 850 national genebanks worldwide will accumulate deleterious mutations over long-term conservation. However, little is known about how mutations accumulate in germplasm under long-term conservation. An attempt was made using seed-based RNA-Seq analysis to identify and characterize deleterious genetic variants in 190 diverse soybean accessions that were conserved since 1972 and were regenerated up to 10 cycles. The analysis identified 588 deleterious variants, which were widely distributed across 20 soybean chromosomes, mostly present in 10 or fewer samples, associated with diverse biological processes, and largely predicted to be weakly and mildly detrimental. Significant differences in estimates of three mutation burdens (total, heterozygous, and homozygous) were found among the samples, including sample groups representing different countries of origin. Total and heterozygous mutation burden estimates were found to increase significantly with the number of conservation years since accession acquisition and the number of germplasm regenerations, but homozygous mutation burden estimates were not correlated with these two conservation-related accession features. Total mutation burden estimates were negatively correlated with expressed gene counts and RNA integrity numbers (RINs) and marginally positively associated with averaged gene expression levels. Correlations were also found among expressed gene count, averaged gene expression level, and RIN value. No significant differences were detected between seed-based and leaf-based estimates of total mutation burden, expressed gene count, averaged expression level, and RIN. These findings provide the first empirical evidence that total mutation burden increased primarily through the accumulation of heterozygous, rather than homozygous, deleterious mutations over successive soybean germplasm regenerations. This insight is useful for conducting informative assessments of deleterious mutation accumulation and enhancing the management and conservation of plant germplasm. Full article

Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article

Background: Severe damage to one side of the brain often leads to adverse consequences and can also cause widespread changes throughout the brain, especially in the contralateral area. Studying molecular changes in the contralateral cerebral hemisphere, especially with regard to genetic regulation, can help discover potential treatment strategies to promote recovery after severe brain trauma on one side. Methods: In our study, the right motor cortex was surgically removed to simulate severe unilateral brain injury, and changes in glial cells and synaptic structure in the contralateral cortex were subsequently assessed through immunohistological, morphological, and Western blot analyses. We conducted transcriptomic studies to explore changes in gene expression levels associated with the inflammatory response. Results: Seven days after corticotomy, levels of reactive astrocytes and hypertrophic microglia increased significantly in the experimental group, while synapsin-1 and PSD-95 levels in the contralateral motor cortex increased. These molecular changes are associated with structural changes, including destruction of dendritic structures and the encapsulation of astrocytes by synapses. Genome-wide transcriptome analysis showed a significant increase in gene pathways involved in inflammatory responses, synaptic activity, and nerve fiber regeneration in the contralateral cortex after corticorectomy. Key transcription factors such as NF-κB1, Rela, STAT3 and Jun were identified as potential regulators of these contralateral changes. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) confirmed that the mRNA expression levels of Cacna1c, Tgfb1 and Slc2a1 genes related to STAT3, JUN, and NF-κB regulation significantly increased in the contralateral cortex of the experimental group. Conclusions: After unilateral brain damage occurs, changes in the contralateral cerebral hemisphere are closely related to processes involving inflammation and synaptic function. Full article

Background/Objectives: Chronic wounds represent a significant clinical and public health challenge due to impaired tissue repair and high associated morbidity. This study investigates the therapeutic potential of the secretome derived from human mesenchymal stem cells obtained from the pulp of deciduous teeth (hDP-MSCs) in promoting skin wound healing. Methods: After confirming the mesenchymal identity and multipotent differentiation potential of hDP-MSCs by using flow cytometry and histological staining, the effects of the secretome on human keratinocyte (HaCaT) cultures were evaluated. Results: Scratch assays, performed under high- and low-glucose conditions, demonstrated that the secretome significantly promoted keratinocyte migration and wound closure without compromising cell viability. Additionally, the secretome modulated the expression of key genes involved in inflammation and tissue regeneration, including IL-1β, TNF-α, TGF-β1, and VEGF-α, in a time-dependent manner. Under inflammatory conditions induced by lipopolysaccharide, co-treatment with the secretome significantly reduced TNF-α expression and increased TGF-β1 expression, suggesting an anti-inflammatory effect. Conclusions: These findings indicate the potential of the hDP-MSC-derived secretome as a promising cell-free therapeutic strategy capable of accelerating skin regeneration and modulating the inflammatory response during the wound healing process. Full article

Skeletal muscle atrophy is a debilitating condition characterized by the loss of muscle mass and function. It is commonly associated with aging, chronic diseases, disuse, and prolonged glucocorticoid therapy. Oxidative stress and catabolic signaling pathways play significant roles in the progression of muscle degradation. Despite its clinical relevance, few effective therapeutic options are currently available. In this study, we investigated the protective effects of an ethanolic extract of Glycine Semen Preparata (GSP), i.e., fermented black soybeans, using in vitro and in vivo models of dexamethasone (Dexa)-induced muscle atrophy. In C2C12 myoblasts and myotubes, GSP significantly attenuated both oxidative stress-induced and Dexa-induced damages by reducing reactive oxygen species levels and by suppressing the expression of the muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1. Moreover, GSP upregulated key genes involved in muscle regeneration (Myod1 and Myog) and mitochondrial biogenesis (PGC1α), indicating its dual role in muscle protection and regeneration. Oral administration of GSP to mice with Dexa-induced muscle atrophy resulted in improved muscle fiber integrity, increased proportion of large cross-sectional area fibers, and partial recovery of motor function. Isoflavone aglycones, such as daidzein and genistein, were identified as active compounds that contribute to the beneficial effects of GSP through antioxidant activity and gene promoter enhancement. Thus, GSP is a promising nutraceutical that prevents or mitigates muscle atrophy by targeting oxidative stress and promoting myogenesis and mitochondrial function. Further studies are warranted to standardize the bioactive components and explore their clinical applications. Full article

β-catenin is a key regulator of osteoblast differentiation, proliferation, and bone homeostasis. Through its interaction with transcription factors such as TCF/LEF, Runx2, and Osx, it coordinates gene expression essential for osteogenesis. The aim of this review is to demonstrate how β-catenin signaling is modulated by various physiological and pathological factors, including mechanical loading, oxidative stress, HIV-1 gp120, fluoride, implant topography, and microRNAs. These factors influence Wnt/β-catenin signaling through different mechanisms, often exerting opposing effects on osteoblast function. By integrating these modulators, we provide a comprehensive view of the dynamic regulation of β-catenin in bone biology. Understanding this complexity may provide insight into novel therapeutic strategies targeting β-catenin in bone regeneration, metabolic bone diseases, and pathologies such as HIV-associated bone loss or osteosarcoma. Full article

Glaucoma is a leading cause of irreversible blindness, normally associated with dysfunction and degeneration of the trabecular meshwork (TM) as the primary cause. Trabecular meshwork stem cells (TMSCs) have emerged as promising candidates for TM regeneration toward glaucoma therapies, yet their molecular characteristics remain poorly defined. In this study, we performed a comprehensive transcriptomic comparison of human TMSCs and human TM cells (TMCs) using RNA sequencing and microarray analyses, followed by qPCR validation. A total of 465 differentially expressed genes were identified, with 254 upregulated in TMSCs and 211 in TMCs. A functional enrichment analysis revealed that TMSCs are associated with development, immune signaling, and extracellular matrix remodeling pathways, while TMCs are enriched in structural, contractile, and adhesion-related functions. A network topology analysis identified CXCL3, CXCL6, and BMP2 as robust TMSC-specific hub genes, and LMOD1 and BGN as TMC-specific markers, with expression patterns confirmed by qPCR. These findings define distinct molecular signatures of TMSCs and TMCs, providing reliable biomarkers for cell identity and a foundation for future stem cell-based therapies targeting TM dysfunction in glaucoma. Full article

Investigating the effects of fire disturbance on soil microbial diversity and nitrogen cycling is crucial for understanding the mechanisms underlying soil nitrogen cycling. This study examined the fire burn site of the Larix gmelinii forest in the Greater Khingan Mountains, Inner Mongolia, to analyze the impact of varying fire intensities on soil nitrogen, microbial communities, and the abundance of nitrogen cycle-related functional genes after three years. The results indicated the following findings: (1) Soil bulk density increased significantly following severe fires (7.06%~10.84%, p < 0.05), whereas soil water content decreased with increasing fire intensity (6.62%~19.42%, p < 0.05). The soil total nitrogen and ammonium nitrogen levels declined after heavy fires but increased after mild fires; (2) Mild fire burning significantly increased soil bacterial diversity, while heavy fire had a lesser effect. Dominant bacterial groups included Xanthobacteraceae, norank_o_norank_c_AD3, and norank_o_Elsterales. Norank_o_norank_c_AD3 abundance decreased with burn intensity (7.90% unburned, 3.02% mild fire, 2.70% heavy fire). Conversely, norank_o_Elsterales increased with burning (1.23% unburned, 5.66% mild fire, 5.48% heavy fire); (3) The abundance of nitrogen-fixing nifH functional genes decreased with increasing fire intensity, whereas nitrification functional genes amoA-AOA and amoA-AOB exhibited the opposite trend. Light-intensity fires increased the abundance of denitrification functional genes nirK, nirS, and nosZ, while heavy fires reduced their abundance; (4) The correlation analysis demonstrated a strong association between soil bacteria and denitrification functional genes nifH and amoA-AOA, with soil total nitrogen being a key factor influencing the nitrogen cycle-related functional genes. The primary bacterial groups involved in soil nitrogen cycling were Proteobacteria, Actinobacteria, and Chloroflexi. These findings play a critical role in promoting vegetation regeneration and rapid ecosystem restoration in fire-affected areas. Full article

Peripheral nerve injury initiates a complex cascade of events coordinating immune responses, extracellular matrix (ECM) remodeling, and neuronal repair. While β2-microglobulin (B2M) is well known for its role in MHC class I-mediated antigen presentation and CD8⁺ T-cell differentiation, its potential contributions to non-immune processes remain underexplored. In this study, we investigated the role of B2M in peripheral nerve regeneration using a chronic constriction injury (CCI) model in wild-type and B2M-deficient (B2M-KO) mice. Flow cytometry, RNA sequencing (RNA-seq), and quantitative PCR (qPCR) were performed to assess T-cell subset dynamics and gene expression following injury. Flow cytometric analysis showed that CD3⁺CD4⁺ and CD3⁺CD8⁺ T-cell populations increased by day 7 post-injury. While CD3⁺CD4⁺ T-cell expansion occurred in both groups, a significant increase in CD3⁺CD8⁺ T cells was observed only in wild-type mice. RNA-seq analysis at 3 days post-injury—prior to substantial T-cell accumulation—revealed marked downregulation of ECM-related genes in B2M-KO mice, including collagens, matrix-associated proteins, and other key ECM components. KEGG analysis identified suppression of ECM–receptor interaction, PI3K-Akt, and TGF-β signaling pathways. qPCR confirmed reduced expression of Thbs1 in B2M-KO mice. These findings suggest that B2M plays a critical, CD8⁺ T-cell-independent role in regulating ECM dynamics and regenerative signaling during early nerve repair, expanding the conceptual framework of B2M’s function beyond classical immune roles. Full article

Traumatic injuries to the peripheral (PNS) and central nervous systems (CNS) trigger distinct regenerative responses, with the PNS displaying limited regenerative capacity and the CNS remaining largely refractory. Recent research highlights the role of epigenetic modifications, particularly histone acetylation, in modulating the gene expression programs that drive axonal regeneration. This review synthesizes current findings on post-translational histone modifications, focusing on histone acetyltransferases (HATs), histone deacetylases (HDACs), and epigenetic readers, in addition to their impact on neuronal and non-neuronal cells following injury. While HATs like p300/CBP and PCAF promote the expression of regeneration-associated genes, HDAC inhibition has been shown to facilitate neurite outgrowth, neuroprotection, and functional recovery in both PNS and CNS models. However, HDAC3, HDAC5, and HDAC6 demonstrate context- and cell-type-specific roles in both promoting and limiting regenerative processes. The review also highlights cell-specific findings that have been scarcely covered in the previous literature. Thus, the immunomodulatory roles of epigenetic regulators in microglia and macrophages, their involvement in remyelination via Schwann cells and oligodendrocytes, and their impact on astrocyte function are within the scope of this review. Closely considering cell-context specificity is critical, as some targets can exert opposite effects depending on the cell type involved. This represents a major challenge for current pharmacological therapies, which often lack precision. This complexity underscores the need to develop strategies that allow for cell-specific delivery or target regulators with converging beneficial effects across cell types. Such approaches may enhance regenerative outcomes after CNS or PNS injury. Full article

Ulva prolifera (Chlorophyta), a pivotal species in green tide generation, is particularly vulnerable to abiotic stressors, including variations in temperature and light intensity, requiring specific regulatory frameworks for survival. Epigenetic modification is recognized as a molecular mechanism contributing to the flexible adaptability to environmental alterations. In this study, using DNA methylation pattern analysis, we investigated abiotic stress responsive methylation events, as well as gene and pathway expression patterns, in green macroalgae U. prolifera cultured under elevated temperature–light stress (30 °C and 300 µmol photons m⁻² s⁻¹⁾ and identified a negative correlation between CG methylation and gene expression patterns which indicated that abiotic stress caused CG demethylation and afterwards provoked the transcription response. CHG and CHH methylation exhibited an increased mutability and were preeminently found in transposable elements and intergenic regions, possibly contributing to genetic stability by restricting transposon activity. Furthermore, a rapid regeneration through spore ejection and the formation of new thalli was observed, which emphasized its tenacity capacity for stress memory. Our study also revealed an upregulation of genes associated with the glycolysis pathway and highlighted the critical roles of hexokinase, 6-phosphofructokinase-1, and fructose-6-phosphate in triggering glycolysis as a significant stress-adaptive pathway. Overall, these findings suggested that DNA methylation functions as a potential regulatory mechanism, maintaining environmental adaptability, genomic integrity, and underpinning regenerative capacity in U. prolifera. The findings elucidated the molecular resilience of U. prolifera, highlighting its feasibility for sustainable development and biotechnological applications. Full article

Androgenetic alopecia (AGA) is marked by the progressive miniaturization of hair follicles (HFs) and hair thinning, driven by a decline in the progenitor cells critical for hair regeneration. Despite this, the mechanisms responsible for progenitor cell depletion remain largely unclear. To investigate transcriptional alterations in the progenitor cell regions of AGA patients while maintaining the spatial tissue context, we employed the GeoMX Digital Spatial Profiling (DSP) platform, which enables a precise comparison with healthy controls. Our analysis revealed the significant upregulation of genes associated with extracellular matrix (ECM) organization and the epithelial–mesenchymal transition (EMT), including FN1, TWIST1, and TGFB2 in the progenitor cell region of the HFs. Correspondingly, protein expression data confirmed increased levels of the protein products of these genes in the affected areas, underscoring their roles in the disease’s progression. These molecular changes suggest an environment conducive to the EMT, potentially contributing to the loss of progenitor cells and indicating a fibrogenic shift within the HF microenvironment. Additionally, our study highlights the influence of peri-infundibular immune cell infiltration on these molecular changes, suggesting that immune-mediated microinflammation may contribute to the fibrogenic environment and progenitor cell loss in the AGA. These findings demonstrate the utility of spatial transcriptomics in identifying potential therapeutic targets and advancing our understanding of AGA’s molecular mechanisms, offering avenues for developing targeted treatment strategies. Full article

Exploring host preference and resource partitioning among seed predator species is essential for understanding the coexistence mechanisms and guiding effective forest pest management. This study aimed to elucidate how seed traits influence infestation dynamics and species interactions, focusing on acorn weevils infesting Quercus mongolica. Species identification and clarification of their evolutionary relationships within the Curculio genus were performed through phylogenetic analyses of the mitochondrial cytochrome c oxidase subunit I gene sequences. The seed infestation patterns were assessed by comparing the infestation rates across various seed size classes. Furthermore, the correlations between the seed morphological traits (length, width, aspect ratio, and weight) and weevil abundance were analyzed. The phylogenetic results revealed well-supported monophyletic clades corresponding to Curculio arakawai and Curculio sikkimensis. This confirmed the clear genetic separation between these two distinct weevil species, thereby substantiating the divergence observed in weevil populations correlated with different seed hosts. The infestation patterns revealed the association of weevil species-specific preferences with seed size: C. arakawai predominantly infested larger acorn seeds, whereas C. sikkimensis predominantly infested smaller acorn seeds. C. sikkimensis favored smaller ones. Both species exhibited positive correlations between abundance and seed length and width in larger seeds; however, the seed weight displayed no significant effect. These results indicate niche differentiation mediated by seed size and morphology, which likely reduced interspecific competition and facilitated coexistence. This study elucidates species-specific host selection patterns in acorn weevils and highlights acorn traits as crucial factors shaping seed predator assemblages. The findings provide valuable insights for developing targeted pest management strategies and supporting sustainable oak forest regeneration. Full article

Skeletal muscle diseases often exhibit fiber-type-specific characteristics and pose substantial clinical challenges, necessitating innovative therapies. The extracellular matrix (ECM) plays a pivotal role in muscle physiology and regeneration, influencing cell differentiation. However, its specific role and mechanisms influencing muscle fiber type specification remain insufficiently understood. In this study, C2C12^GFP myoblasts were differentiated into myofibers on plates coated with fibronectin, Collagen I, and Geltrex™. Differentiation occurred successfully across all ECM substrates, resulting in myofiber formation. Quantitative polymerase chain reaction (qPCR) analysis confirmed myogenic marker expression patterns, indicating decreased Pax7 and increased Myog levels by day 7. Protein analysis through Western blot and immunofluorescence assays along with transcriptomic profiling through RNA sequencing consistently indicated that Collagen I promoted slow-type fibers development, as evidenced by increased slow myofiber protein expression and the upregulation of slow fiber-associated genes, potentially mediated by pathways involving calcineurin/NFAT, MEF2, MYOD, AMPK, PI3K/AKT, and ERK1. In contrast, fibronectin and Geltrex™ led to fast-type fiber development, with elevated fast-type fiber protein levels and upregulation of fast fiber-associated genes, possibly through activation of HIF1A, FOXO1, NFKB, and ERK2. These findings elucidate ECM-mediated muscle fiber type differentiation mechanisms, informing future targeted therapies for muscle regeneration. Full article