Animal Cells and Systems最新文献

Invasive species can be unpredictable in their ability to adapt and spread across novel landscapes. American bullfrogs (Lithobates catesbeianus) and red-eared sliders (Trachemys scripta elegans) have become invasive in South Korea since their introduction in the 1970s through the food and pet trades. One of the first steps to their population regulations is to determine each species' distribution in the country, which will allow for the identification of at-risk areas. In this study, we used a combination of kernel density and habitat suitability modeling to identify regions of current invasion and future spread for both species. We additionally modeled habitat suitability under a variety of climate scenarios, spanning 2021-2100 in order to determine possible climate change-based spread. For L. catesbeianus we found the total possible invasible area to be 46.2% of the country under current climate conditions, with 26.5% of the country currently invaded. For T. scripta, we found the total possible invasible area to be 38.5% of the country under current climate conditions, with 2.1% currently invaded. Finally, based on climate change predictions, both species are expected to have a decreased range of suitable area in the coming decades. The variations between the two invasive species pertain to their different breeding ecology.

Inflammatory bowel disease is a chronic condition characterized by inflammation of the gastrointestinal tract, resulting from an abnormal immune response to normal stimuli, such as food and intestinal flora. Since the etiology of this disease remains largely unknown, murine models induced by the consumption of dextran-sodium sulfate serve as a pivotal tool for studying colon inflammation. In this study, we employed both acute and chronic colitis mouse models induced by varying durations of dextran-sodium sulfate consumption to investigate the pathological and immunologic characteristics throughout the disease course. During the acute phase, activated innate inflammation marked by M1 macrophage infiltration was prominent. In contrast, the chronic phase was characterized by tissue remodeling, with a significant increase in M2 macrophages and lymphocytes. RNA-sequencing revealed genetic changes in acute and chronic colitis, marked by the maintenance of genomic integrity in the acute phase and extracellular matrix dynamics in the chronic phase. These phase-specific alterations reflect the multifaceted physiological processes involved in the initiation and progression of inflammation in the large intestine, underscoring the necessity for distinct experimental approaches for each phase. The findings demonstrate that the factors shaping the large intestinal immune microenvironment change specifically during the acute and chronic phases of experimental inflammatory bowel disease, highlighting the importance of developing therapeutic strategies that align with the disease course.

Osmoregulation is essential for the survival of aquatic organisms, particularly teleost fish facing osmotic challenges in environments characterized by variable salinity. While the gills are known for ion exchange, the intestine's role in water and salt absorption is gaining attention. Here, we investigated the adaptive responses of the intestine to salinity stress in guppies (Poecilia reticulata), observing significant morphological and transcriptomic alterations. Guppies showed superior salt tolerance compared to zebrafish (Danio rerio). Increasing salinity reduced villus length and intestinal diameter in guppies, while zebrafish exhibited damage to villus structure and loss of goblet cells. Transcriptomic analysis identified key genes involved in osmoregulation, tissue remodeling, and immune modulation. Upregulated genes included the solute carrier transporters slc2al and slc3al, which facilitate ion and water transport, as well as a transcription factor AP-1 subunit and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta, both of which participate in tissue repair and growth responses. In contrast, many genes related to the innate immune system (such as Tnfaip6) were downregulated, suggesting a shift toward the prioritization of osmoregulatory functions over immune responses. Interestingly, the differential expression of adaptation genes was linked to variations in epigenetic modifications and transcription factor activity. Transcription factors crucial for adapting to salt stress, such as bhlhe40, cebpd, and gata6, were progressively upregulated in guppies but remained downregulated in zebrafish. Our findings highlight the intricate mechanisms of adaptation to salinity stress in P. reticulata, providing insights into osmoregulatory mechanisms involving the intestine in aquatic organisms.

Dynamic modeling of cellular states has emerged as a pivotal approach for understanding complex biological processes such as cell differentiation, disease progression, and tissue development. This review provides a comprehensive overview of current approaches for modeling cellular state dynamics, focusing on techniques ranging from dynamic or static biomolecular network models to deep learning models. We highlight how these approaches integrated with various omics data such as transcriptomics, and single-cell RNA sequencing could be used to capture and predict cellular behavior and transitions. We also discuss applications of these modeling approaches in predicting gene knockout effects, designing targeted interventions, and simulating organ development. This review emphasizes the importance of selecting appropriate modeling strategies based on scalability and resolution requirements, which vary according to the complexity and size of biological systems under study. By evaluating strengths, limitations, and recent advancements of these methodologies, we aim to guide future research in developing more robust and interpretable models for understanding and manipulating cellular state dynamics in various biological contexts, ultimately advancing therapeutic strategies and precision medicine.

βPix is a guanine nucleotide exchange factor for the Rac1 and Cdc42 small GTPases, which play important roles in dendritic spine morphogenesis by modulating actin cytoskeleton organization. The formation and plasticity of the dendritic spines are essential for normal brain function. Among the alternatively spliced βPix isoforms, βPix-b and βPix-d are expressed specifically in neurons. Our previous studies using cultured hippocampal neurons identified the roles of βPix-b and βPix-d in spine formation and neurite development, respectively. Here, we analyzed the in vivo role of the neuronal βPix isoforms in brain development and function by using βPix neuronal isoform knockout (βPix-NIKO) mice, in which the expression of the βPix-b and βPix-d isoforms is blocked, while the expression of the ubiquitous βPix-a isoform is maintained. Loss of the neuronal βPix isoforms leads to reduced activity of Rac1 and Cdc42, decreased dendritic complexity and spine density, and increased GluN2B and Ca²⁺/calmodulin-dependent protein kinase IIα expression in the hippocampus. The defects in neurite development, dendritic spine maturation, and synaptic density in cultured βPix-NIKO hippocampal neurons were rescued by the expression of βPix-b or βPix-d. In behavioral studies, βPix-NIKO mice exhibited robust deficits in novel object recognition and decreased anxiety levels. Our findings suggest that neuronal morphogenetic signaling by the neuronal βPix isoforms contributes to normal behaviors.

Interferon gamma (IFNγ) is well-known for its ability to stimulate immune cells in response to pathogen infections and cancer. To develop an effective cancer therapeutic vaccine, CT26 colon carcinoma cells were genetically modified to express IFNγ either as a secreted form (sIFNγ) or as a membrane-bound form. For the membrane-bound expression, IFNγ was fused with Fas (mbIFNγ/Fas), incorporating the extracellular cysteine-rich domains, transmembrane, and cytoplasmic domains of Fas. The tumor cells expressing sIFNγ and mbIFNγ/Fas showed slower growth rates compared to the mock-transfected cells. Furthermore, the tumorigenicity of the CT26 cells expressing mbIFNγ/Fas was significantly lower than that of cells expressing sIFNγ or the mock control. Remarkably, about 85% of the mice injected with the mbIFNγ/Fas-expressing tumors remained tumor-free for over two months. Mice that rejected mbIFNγ/Fas-expressing tumors developed systemic anti-tumor immunity against CT26 cells, which was characterized by enhanced levels of CD4⁺ and CD8⁺ T cells, as well as natural killer (NK) cells. Interestingly, splenocytes activated with the mbIFNγ/Fas-expressing tumors exhibited higher cytotoxicity than those activated with tumor cells expressing sIFNγ. These findings suggest that expressing the mbIFNγ/Fas chimera in tumor cells could be a promising strategy for developing whole tumor cell vaccines or gene therapies for cancer immunotherapy.

Tissue growth is controlled by various signaling pathways, such as the insulin/IGF-signaling (IIS) pathway. Although IIS activation is regulated by a complex regulatory network, the mechanism underlying miRNA-based regulation of the IIS pathway in Drosophila wing development remains unclear. In this study, we found that the wing size of adult flies was negatively affected by miR-263b expression. The miR-263b-mediated alteration in wing size was linked to a reduction in wing cell number. Additionally, miR-263b overexpression in Drosophila S2 cells decreased cell proliferation and increased cell death. Consequently, we identified Akt as a direct target of miR-263b-5p and found that miR-263b-mediated wing growth regulation was due to changes in Akt expression. Co-expression of Akt in miR-263b-overexpressing wings rescued the miR-263b overexpression-mediated reduction in wing growth. These results enhance our understanding of the crucial role of miRNAs in growth regulation during Drosophila wing development.

Parvimonas micra (Pm), a periodontal pathogen, has been implicated in the impairment of anti-tumor responses in colorectal cancer (CRC). The tumor microenvironment in CRC involves tumor-associated macrophages (TAMs), which are pivotal in modulating tumor-associated immune responses. The polarization of TAMs towards an M2-like phenotype promotes CRC progression by suppressing the immune system. However, the mechanisms by which Pm affects the progression of CRC remain inadequately elucidated. In this study, we explored the impact of Pm infection on CRC cell characteristics, including proliferation, chemoresistance, migration, and macrophage polarization. We found that Pm-infected THP-1-derived macrophages exhibited elevated interleukin-10 levels, a well-established M2 marker. Conditioned media from Pm-treated THP-1 cells significantly enhanced CRC cell proliferation, cisplatin resistance, and migration, and interleukin-8 was identified as a key factor. Consistent with the in vitro results, an azoxymethane/dextran sodium sulfate mouse model treated with oral Pm showed accelerated CRC tumor growth. These results offer mechanistic insights into the influence of Pm infection on tumor microenvironment in CRC through M2-like macrophage polarization. The identified pathways may serve as potential targets for therapeutic interventions for CRC.

Purpose: Diabetic cardiomyopathy (DCM) is a major complication of type 2 diabetes mellitus (T2DM), but its effective prevention and treatment are still limited. We investigated the effects of GYY4137, a slow-releasing hydrogen sulfide donor, and its downstream mediator forkhead box protein O1 (FOXO1) on T2DM-associated DCM. Methods: In vivo, T2DM mice were induced by a high-fat diet coupled with streptozotocin injection. Intragastric administration of GYY4137 was also performed. In vitro, AC16 cardiomyocytes were treated with glucose and palmitate to mimic high-glucose and high-fat (HGHF) conditions, in which GYY4137 or a FOXO1 inhibitor (AS1842856) was also introduced. Bioinformatics analysis was performed using public GEO datasets. Results: GYY4137 demonstrated a protective effect against cardiac dysfunction, fibrosis, and autophagy in cardiac tissues of T2DM mice. Moreover, GYY4137 alleviated cell injury and lipid accumulation in HGHF-treated AC16 cells. In both in vivo and in vitro models, hyperactivation of autophagy was dampened by GYY4137. Bioinformatic analysis revealed the potential role of the FOXO pathway and autophagy in DCM. Further experiments showed that GYY4137 rescued diabetes-induced overexpression of FOXO1. AS1842856 displayed a notable capacity to shield cardiomyocytes against diabetes-induced injury similar to that achieved by GYY4137. Conclusion: GYY4137 protected against cardiac dysfunction and fibrosis in T2DM mice, and the mechanism might involve suppression of FOXO1-induced autophagy.

Insect protein hydrolysates (PH) are emerging as valuable compounds with biological activity. The aim of the present study was to assess the potential cytoprotective effects of PH from the Black Soldier Fly (BPH, in the range 0.1-0.5 mg/mL) against inflammatory conditions and oxidative stress in LPS-challenged L-929 cells. BPH was effective in inhibiting LPS-induced ROS and nitrite production and in reducing the protein and transcript levels of remarkable inflammatory markers, such as TNF-α, IL-6, IL-1α, and IL-1β, as determined by ELISA and/or qPCR. Moreover, the BPH antioxidant and anti-inflammatory activities rely on the induction of selected genes and proteins involved in the antioxidant response (i.e. Cu/ZnSod, MnSod, Gpx, HO-1) through Nrf2, as well as on the inhibition of the activation of NF-κB, a key player in inflammation. These findings suggest that BPH represents effective bioactive compounds with therapeutic potential for mitigating oxidative stress and inflammation in vitro, thus deserving further investigation into the underlying mechanisms before BPH application as novel drugs in the near future.