Animal Cells and Systems最新文献

Mesenchymal stem cells (MSCs) integrate mechanical information from their microenvironment to regulate lineage commitment. Through integrin-based adhesion, cytoskeletal tension, and nuclear deformation, mechanical cues are transduced into intracellular signals via conserved pathways such as integrin-FAK/Src, RhoA-ROCK, and Hippo-YAP/TAZ. These pathways not only regulate chromatin accessibility and transcriptional output but also induce characteristic changes in mechanosensitive microRNAs (miRNAs). Mechanical loading alters miRNA expression programs that modulate focal adhesion assembly, Rho GTPase activity, and SMAD or Wnt signaling, thereby refining the SOX9-centered transcriptional networks that drive MSC chondrogenesis. Physiological mechanical stimuli including dynamic compression, fluid shear, and controlled tensile strain promote chondrogenic differentiation by lowering actomyosin tension, restricting YAP/TAZ nuclear localization, and enhancing SMAD-SOX9 cooperation. Conversely, pathological changes in the pericellular matrix, such as reduced stiffness and increased permeability, disrupt mechanical filtering, impair force transmission, and destabilize cytoskeletal organization. These mechanical defects shift chondrocytes toward high-tension, YAP-active states that suppress matrix gene expression and hinder maintenance of the chondrogenic phenotype. Simultaneously, dysregulation of mechanosensitive miRNAs weakens negative regulation of inflammatory and catabolic pathways, contributing to extracellular matrix degradation and progressive cartilage degeneration. Although numerous mechanosensitive miRNAs have been identified, their mechanistic roles and context-specific regulation remain incompletely defined. A deeper understanding of how miRNAs integrate diverse mechanical cues is essential to elucidate MSC fate transitions and the mechanobiology of cartilage repair. Advances in single-cell mechanobiology, mechanically tunable culture systems, and miRNA-targeted modulation may ultimately yield diagnostic indicators of mechanical imbalance and new therapeutic strategies for restoring cartilage homeostasis.

Quercus infectoria galls (QIG), traditionally used in Asian and Middle Eastern medicine, have shown lipid-lowering activity by reducing cholesterol, triglycerides, and low-density lipoprotein (LDL) levels. However, their role in regulating adipocyte lipid metabolism remains unexplored. This study aimed to evaluate the anti-obesity potential of QIG extract by investigating its regulatory effects on adipogenesis and lipolysis. The regulatory effects of QIG extract on lipid metabolism were investigated using 3T3-L1 adipocytes. The phytochemical profile of the extract was characterized by LC-QTOF-MS, revealing abundant phenolic constituents, including gallic acid, ellagic acid, and various hydrolyzable tannins. Functional assays demonstrated that the extract markedly suppressed lipid accumulation in a dose-dependent manner, achieving a maximum inhibition of 94.52 ± 2.29% without cytotoxicity. Mechanistically, QIG extract induced G1/S cell cycle arrest, suppressed mitotic clonal expansion, and downregulated key adipogenic transcription factors, adipocyte marker genes, as well as lipogenesis-related genes. In mature adipocytes, the extract significantly promoted lipolysis, increasing glycerol release up to 175.55 ± 5.26% of control levels (p < 0.05). In addition, QIG extract-treated adipocytes exhibited reduced intracellular lipid accumulation and smaller lipid droplets, highlighting its capacity to counteract both adipocyte hyperplasia and hypertrophy. Collectively, these findings provide novel mechanistic evidence that QIG extract exerts dual anti-obesity effects by inhibiting adipogenesis and enhancing lipolysis, supporting its potential development as a natural therapeutic candidate for obesity prevention and metabolic disorder management.

Understanding the population genetic structure of marine decapods is essential for their effective conservation and management, particularly for species like the Chinese mitten crab (Eriocheir sinensis), which exhibits a complex life cycle and high invasive potential. In this study, we applied a population genomics approach using SLAF-seq to generate genome-wide SNP data from 120 unrelated individuals collected across six locations in China and Korea. We found a fine-scale but discernible level of genetic differentiation by regional populations correlated with geography. Individuals from Seocheon (Korea) and Wenzhou (southeastern China) exclusively share a distinct genetic ancestry component that makes them divergent from the rest, which we speculate may have been introduced by hybridization with congeneric species. We detected genetic outliers (9 out of 120 individuals) that show ongoing long-distance dispersal along the coastline of the Yellow Sea, likely happening during the planktonic larval phase. Collectively, our findings provide a genomic basis for delineating management strategies, supporting informed stock enhancement, and guiding region-specific conservation efforts for E. sinensis across East Asia.

Animal-vehicle collisions (AVCs) substantially contribute to wildlife population decline and adversely impact threatened species with already limited numbers. In this study, we aimed to investigate the factors contributing to AVCs involving two threatened species in the Republic of Korea: the leopard cat (Prionailurus bengalensis) and Eurasian otter (Lutra lutra). These two species are the most frequently affected by AVCs among threatened mammals in Korea. To achieve this, we used data from the Korea Roadkill Observation System (KROS), a government-sponsored web-based AVC monitoring system. Our analysis focused on 17 variables, categorized into bioclimatic, landscape, and traffic factors, using machine-learning-based predictive modeling. From 2019 to 2021, 589 AVC incidents of P. bengalensis and 228 AVC incidents of L. lutra were recorded in KROS. Our findings indicate that AVC frequencies peaked during the most active seasons of the year, corresponding to the mating or dispersal periods, with P. bengalensis showing the highest AVC frequency in fall and L. lutra peaking in summer. For P. bengalensis, habitat suitability consistently exerted a strong influence on AVC risk across all seasons, whereas for L. lutra, the key factors affecting AVC risk highly varied seasonally. These results underscore the importance of seasonal and species-specific approaches for AVC mitigation. Targeted strategies, including wildlife corridors, underpasses, and speed reduction zones in high-risk areas, are recommended to mitigate AVC risks. By identifying the key factors and their seasonal dynamics, this study provides critical insights for conserving threatened wildlife and effectively reducing AVC incidents.

Mitochondrial genomes (mitogenomes) are powerful molecular tools for exploring phylogenetic relationships, deciphering adaptation and divergence, as well as disease transmission potential among insects. In this study, we performed a comparative mitogenomic and phylogenetic analysis of two major mosquito vectors - Aedes albopictus and Culex pipiens molestus - collected from South Korea, together with mitogenome data from 18 additional mosquito species representing three Culicidae genera (Aedes, Anopheles, and Culex) retrieved from GenBank. The assembled mitogenomes, each comprising 13 protein-coding genes, 22 tRNAs, and two rRNAs, revealed conserved gene order and structural features typical of Diptera. Comparative analyses with multiple species representing the three genera uncovered lineage-specific patterns in codon usage, base composition, and control region variability. Phylogenetic relationships inferred using maximum likelihood and Bayesian methods based on concatenated mitochondrial protein-coding genes robustly resolved genus-level relationships and supported the monophyly of the two major Culicidae clades, Aedes (tribe Aedini) and Culex (tribe Culicini), with Anopheles sinensis and Anopheles gambiae serving as outgroups. Time-calibrated Bayesian analyses indicated a deep divergence between Anopheles and the Aedes-Culex clade during the Paleogene (∼51.8 Mya), followed by the separation of Aedes and Culex around ∼39.7 Mya. Notably, Ae. albopictus diverged from its congeners ∼11.7 Mya, while Cx. p. molestus exhibited a much more recent divergence (∼2.35 Mya), suggesting distinct evolutionary pressures and histories. This study demonstrates the utility of mitogenomic data for reconstructing mosquito evolutionary history and provides insights relevant to vector biology, ecology, and public health.

Depression induce by chronic neuroinflammation disrupts daily life and work, underscoring the importance of its treatment. It this study, depressive- and anxiety-like behaviors were induced in mice by injecting bacillus Calmette-Guérin (BCG), resulting from chronic neuroinflammation. Daily stimulation with specific acupuncture points (Baihui and Yintang, GV20 and GV29) with electroacupuncture (EA) for 14 days significantly alleviated depressive- and anxiety-like behaviors. Additionally, it also markedly reduced the levels of pro-inflammatory cytokines, including interleukin (IL)-6, IL-1β, and tumor necrosis factor-α, as well as inflammatory markers such as cyclooxygenase-2, in both the plasma and hippocampus. EA Stimulation significantly increased brain-derived neurotrophic factor (BDNF) mRNA expression in the hippocampus. Our results demonstrated that EA stimulation improved depression- and anxiety-like behaviors induced by chronic inflammation, an effect associated with the decreased expression of BDNF via regulation of NF-κB pathway.

Anomura is a morphologically and ecologically diverse infraorder of decapod crustaceans, yet its evolutionary and phylogenetic patterns remain underexplored using mitochondrial genome-based approaches, particularly regarding adaptive evolution across diverse environments. Here, we present a comprehensive phylogenomic analysis of 42 anomuran mitochondrial genomes, including three newly sequenced species: two intertidal Hapalogastrinae (Hapalogaster dentata and Oedignathus inermis) and one deep-sea pagurid (Pagurus rathbuni). The arrangement of protein-coding genes was identical to that reported in previously studied Lithodidae and Paguridae species; however, several tRNA genes exhibited translocations. Moreover, more than half of the 22 tRNA genes were predicted to adopt atypical cloverleaf form, and all protein-coding genes were under purifying selection. In addition, analysis of the mitochondrial control region revealed a conserved repeat structure (∼47 bp motif repeated ∼3.6 times), from which depth-associated Gibbs free energy patterns were broadly inferred. These patterns suggest potential links between control-region stability, depth-dependent adaptation, and the evolutionary process of carcinization. Time-calibrated analyses suggest that H. dentata and O. inermis diverged from other lithodids approximately 37-50 million years ago, while P. rathbuni diverged around 32 million years ago. These divergence events coincide with the Eocene-Oligocene transition, a period characterized by global cooling, sea-level decline, and shifts in ocean circulation. This temporal correspondence suggests that such environmental changes may have been associated with the diversification and adaptive evolution of Anomura. Overall, this study advances our understanding of anomuran phylogeny and highlights the complex interplay among adaptation to the environment, carcinization, and mitochondrial genome evolution.

Non-coding RNAs (ncRNAs) are RNA molecules that are not translated into proteins. Recent advances in RNA biology have uncovered roles of ncRNAs in physiological processes, including aging. Here, we review how various classes of ncRNAs regulate aging and longevity, by focusing on recent research using the nematode Caenorhabditis elegans, an excellent model for aging research. We also discuss the potential of ncRNAs as diagnostic biomarkers and therapeutic targets for aging and age-related diseases. Because many aging-regulating genes and pathways in C. elegans are evolutionarily conserved, our review will provide important information regarding the functions of ncRNAs in aging and longevity in other species, including mammals.

Oral lichen planus (OLP) is a chronic inflammatory condition characterized by CD8+ T cell-mediated apoptosis of oral epithelial cells. While psychological stress has been implicated in OLP pathogenesis, the underlying mechanisms remain unclear. This study explores the role of epinephrine, a primary stress-related catecholamine, in OLP progression. We found that high concentrations of epinephrine induce cytotoxicity in oral keratinocytes, marked by reduced cell viability and increased DNA damage. High-dose epinephrine also elevates oxidative stress by downregulating antioxidant proteins SOD2 and SESN2. Additionally, it activates the STAT3 signaling pathway through both alpha- and beta-adrenergic receptors. Furthermore, epinephrine increases levels of HMGB1 and extracellular ATP, key damage-associated molecular patterns (DAMPs) that could perpetuate chronic inflammation in OLP. These findings suggest that stress-induced epinephrine may exacerbate OLP by promoting oxidative stress, epithelial damage, and immune activation. Given the increased vascularization in OLP lesions, epinephrine's effects may be amplified in affected tissues. Understanding the link between stress and OLP pathogenesis could provide new therapeutic targets for managing this condition.

Colorectal cancer (CRC) is a challenging disease. Recent studies have gradually emphasized the development of novel immunotherapies rather than traditional treatments. Toll-like receptor (TLR) agonists are critical in innate immune responses to orchestrate anti-tumor efficacies, which are attributed to their aptitude to stimulate antigen-presenting cells (APCs) and thus activate tumor-specific T cells. Although several TLR agonists have been proposed for treating tumors, their therapeutic efficacy remains controversial. Therefore, the current study aimed to develop a novel TLR2 agonist, Amuc_1100 C-terminal (Amuc_C), a purified membrane protein from Akkermansia muciniphila (A. muciniphila), and evaluate its anti-tumor properties. Herein, a murine CRC model, CT26, was employed. Tumor-bearing mice received intertumoral treatment with Amuc_C. The anti-tumor effects were determined by flow cytometry, cytokine enzyme-linked immunosorbent assay (ELISA), and immunofluorescence assays. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was then employed to uncover the potent mechanisms. Amuc_C significantly increased the amounts of tumor-infiltrating lymphocytes and systemic immune cells, especially cytotoxic T cells, M1 macrophages, and type 1 dendritic cells. Furthermore, Amuc_C triggered IL-1β, TNF-α, and IFN-γ productions, significantly decreasing tumor growth, and prolonged overall survival. The immunotherapeutic mechanisms revealed by proteomics data were related to the activation of immune responses, the induction of cell cycle arrest, and the inhibition of cell proliferative signaling pathways. In summary, the current study has demonstrated that administration of Amuc_C improves the APCs and escalates adaptive anti-tumor immunity. With the demand for effective anti-tumor treatments, our results provide a compelling proof-of-concept of a TLR2 agonist for cancer immunotherapy.