Animal Cells and Systems最新文献

Esophageal squamous cell carcinoma (ESCC) is an aggressive malignant neoplasm, and up to now, the role of long non-coding RNA (lncRNA) AP001885.4 in cancer, including ESCC, is absolutely unclear. The GEPIA database was applied to identify differentially expressed and prognosis-associated genes in esophageal cancer (ESCA). CCK-8, colony formation, Western blot, and qRT-PCR methods were harnessed to investigate the role and mechanism of AP001885.4 in esophageal carcinogenesis. By analyzing TCGA data in the GEPIA database, two lncRNAs were selected. AP001885.4 was overexpressed and positively associated with the unfavorable outcome of ESCC patients, and LINC001786 was under-expressed and negatively linked with the poor prognosis. Knockdown of AP001885.4 suppressed the proliferation and colony formation of ESCC cells. Importantly, the silence of AP001885.4 downregulated c-myc. Mechanically, the knockdown of AP001885.4 reduced METTL3 expression and m6A modification in c-myc mRNA, and METTL3 positively regulated c-myc. Furthermore, the knockdown of AP001885.4 diminished histone lactylation and NF-κB (p65) expression, and the protein lactylation inhibitors (2-DG, 2-deoxy-D-glucose and oxamate) and the NF-κB inhibitor (JSH-23) also lessened c-myc expression. Consequently, our findings suggested that AP001885.4 promoted the proliferation of esophageal squamous cell carcinoma cells by histone lactylation- and NF-κB (p65)-dependent transcription activation and METTL3-mediated mRNA stability of c-myc.

Bisphenol A (BPA), an endocrine-disrupting substance commonly found in plastics and receipts, is associated with adverse effects, including endocrine disorders, reduced fertility, and metabolic issues. To gain insights into its effects on biological systems, we observed the adverse effects of BPA in male Institute of Cancer Research (ICR) mice exposed to BPA at the lowest observed adverse effect level for 6 weeks, in comparison with the control groups. We constructed a comprehensive transcriptome profile using 20 different tissues to analyze the changes in the whole-body systems. This involved employing differential gene expression, tissue-specific gene, and gene co-expression network analyses. The study revealed that BPA exposure led to significant differences in the transcriptome in the thymus, suggesting activation of T-cell differentiation and maturation in response to BPA treatment. Furthermore, various tissues exhibited immune response activation, potentially due to the migration of immune cells from the thymus. BPA exposure also caused immune-related functional changes in the colon, liver, and kidney, as well as abnormal signaling responses in the sperm. The transcriptome analysis serves as a valuable resource for understanding the functional impact of BPA, providing profound insights into the effects of BPA exposure and emphasizing the need for further research on potential associated health risks.

Osteocytes are located in the lacunae of fluid-filled bone and communicate with neighboring or distant cells by secreting small extracellular vesicles (sEVs) and growth factors as well as via dendrite-dendrite direct connections. However, the mechanism regulating sEV production in osteocytes is yet to be elucidated. In this study, we investigated sEV production and its underlying mechanism in osteocytes cultured on a three dimensional (3D) scaffold. We employed a perfusion system to apply shear stress stimulation to MLO-Y4 cells cultured on a 3D biphasic calcium phosphate (BCP) scaffold and analyzed sEV production and gene expression using RNA sequencing. We found that the expression of genes associated with sEV biogenesis and the secretory pathway were enhanced by fluid shear stress in MLO-Y4 cells cultured on a 3D BCP scaffold. In particular, fluid shear stress induced the expression of Ank, a pyrophosphate transporter, in 3D-cultured MLO-Y4 cells. The role of Ank in sEV production was further examined. Probenecid, an Ank inhibitor, significantly suppressed shear stress-induced sEV production, whereas Ank cDNA overexpression stimulated it. The inhibition of shear stress-induced sEV production by probenecid was recovered by the exogenous addition of pyrophosphate to MLO-Y4 cells. These findings suggest that shear stress-mediated sEV production in 3D-cultured osteocytes is regulated by extracellular pyrophosphate transported by Ank.

Viruses have long been recognized as significant pathogens, contributing to multiple global pandemics throughout human history. Recent examples include the 2009 influenza pandemic and the COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. Despite ongoing experimental and clinical efforts, the development of effective antiviral treatments and vaccines remains challenging due to the high mutation rates of many human pathogenic viruses including influenza virus and SARS-CoV-2. As an alternative approach, antiviral strategies targeting host factors shared by multiple viruses could provide a more universally applicable solution. Emerging evidence suggests that viruses exploit the host cytoskeletal network to facilitate efficient viral replication and propagation. Therefore, a comprehensive understanding of the interactions between viral components and the cytoskeletal machinery may offer valuable insights for the development of broad-spectrum antiviral therapeutics. This review compiles and discusses current knowledge on the interactions between viruses and cytoskeletal elements, including kinesin, dynein, myosin, and vimentin, and explores their potential as therapeutic targets. The potential for these cytoskeletal components to serve as targets for new antiviral interventions is discussed in the context of diverse human viruses, including influenza virus, SARS-CoV-2, herpes simplex virus, human papillomavirus, and human immunodeficiency virus.

Quantum dots have diverse biomedical applications, from constructing biological infrastructures like medical imaging to advancing pharmaceutical research. However, concerns about human health arise due to the toxic potential of quantum dots based on heavy metals. Therefore, research on quantum dots has predominantly focused on oxidative stress, cell death, and other broader bodily toxicities. This study investigated the toxicity and cellular responses of mouse embryonic stem cells (mESCs) and mouse adult stem cells (mASCs) to nitrogen-doped carbon quantum dots (NCQDs) made of non-metallic materials. Cells were exposed to NCQDs, and we utilized a fluorescent ubiquitination-based cell system to verify whether NCQDs induce cytotoxicity. Furthermore, we validated the differentiation-inducing impact of NCQDs by utilizing embryonic stem cells equipped with the Oct4 enhancer-GFP reporter system. By analyzing gene expression including Crebzf, Chop, and ATF6, we also observed that NCQDs robustly elicited endoplasmic reticulum (ER) stress. We confirmed that NCQDs induced cytotoxicity and abnormal differentiation. Interestingly, we also confirmed that low concentrations of NCQDs stimulated cell proliferation in both mESCs and mASCs. In conclusion, NCQDs modulate cell death, proliferation, and differentiation in a concentration-dependent manner. Indiscriminate biological applications of NCQDs have the potential to cause cancer development by affecting normal cell division or to fail to induce normal differentiation by affecting embryonic development during pregnancy. Therefore, we propose that future biomedical applications of NCQDs necessitate comprehensive and diverse biological studies.

Burn injuries, affecting local skin disruption as well as inducing systemic inflammatory responses, are presented as a global public health problem. To enhance the effects of burn wound healing, treatment must simultaneously regulate both re-epithelialization and hyperinflammation. Extracts of Sargassum horneri (S. horneri) have shown a potential to enhance skin wound healing through antioxidative properties, immune enhancement, and modulation of inflammatory responses. However, despite its promising application for burn wound healing, specific investigation into S. horneri-derived compounds for enhancing wound healing has not yet been conducted. In this research, we investigated the burn wound-healing effect of the low-temperature pulverization-specific S. horneri extract (LPSHE), which could not be detected using the room-temperature grinding method. In a mouse burn model with third-degree burn injuries, LPSHE accelerated re-epithelialization by promoting the increase in F-actin formation and reduced burn-induced ROS levels. Additionally, LPSHE significantly regulated hyperinflammation by reducing pro-inflammatory cytokines. Further investigation into molecular mechanisms using HaCaT keratinocytes also demonstrated beneficial effects on burn wound healing. Taken together, our findings suggested that LPSHE is a promising therapeutic candidate for enhancing burn wound healing. Furthermore, this research underscored the importance of low-temperature pulverization in discovering novel natural compounds from marine organisms.

Calcium ions (Ca²⁺) play pivotal roles in regulating numerous cellular functions, including metabolism and growth, in normal and cancerous cells. Consequently, Ca²⁺ signaling is a vital determinant of cell fate and influences both cell survival and death. These intracellular signals are susceptible to modulation by various factors, including changes in the extracellular environment, which leads to mechanical alterations. However, the effect of extracellular matrix (ECM) stiffness variations on intracellular Ca²⁺ signaling remains underexplored. In this study, we aimed to elucidate the mechanisms of Ca²⁺ regulation through the mitochondria, which are crucial to Ca²⁺ homeostasis. We investigated how Ca²⁺ regulatory mechanisms adapt to different levels of ECM stiffness by simultaneously imaging the mitochondria and endoplasmic reticulum (ER) in live cells using genetically encoded biosensors. Our findings revealed that the uptake of mitochondrial Ca²⁺ through Voltage-Dependent Anion Channel 1 (VDAC1), facilitated by intracellular tubulin, is influenced by ECM stiffness. Unraveling these Ca²⁺ regulatory mechanisms under various conditions offers a novel perspective for advancing biomedical studies involving Ca²⁺ signaling.