Mouse model

Bone marrow-derived mesenchymal stem cells (BMSCs) can ameliorate a variety of lung diseases such as asthma, lung fibrosis, and acute lung injury by its anti-inflammatory and immunmodulatory effects. In this study, we developed a mouse model of bronchiolitis obliterans (BO) and evaluated the effects of the intraperitoneal administration of BMSCs on lung histopathology and cytokine levels. 25 BALB/c mice were divided into four groups; control group (Group I), BO developed and 1x106 BMSCs-injected group (Group II), non-BO, 1x106 BMSCs-injected group (Group III), and BO developed and saline-injected group (Group IV)...

Reduction in nucleotide pools through the inhibition of mitochondrial enzyme dihydroorotate dehydrogenase (DHODH) has been demonstrated to effectively reduce cancer cell proliferation and tumour growth. The current study sought to investigate whether this antiproliferative effect could be enhanced by combining Chk1 kinase inhibition. The pharmacological activity of DHODH inhibitor teriflunomide was more selective towards transformed mouse embryonic fibroblasts than their primary or immortalised counterparts, and this effect was amplified when cells were subsequently exposed to PF477736 Chk1 inhibitor...

Ataxia-Telangiectasia mutated (ATM) kinase participates in multiple networks, including DNA damage response, oxidative stress, and mitophagy. ATM also supports replication of diverse DNA and RNA viruses. Gammaherpesviruses are prevalent cancer-associated viruses that benefit from ATM expression during replication. This proviral role of ATM had been ascribed to its signaling within the DNA damage response network; other functions of ATM have not been considered. In this study increased type I interferon (IFN) responses were observed in ATM deficient gammaherpesvirus-infected macrophages...

Korean field mouse (<i>Apodemus peninsulae</i>) shows a wide variation in the number of B chromosomes composed of constitutive heterochromatin. For this reason, it provides a good model to study the influence of the number of centromeres and amount of heterochromatin on spatial organization of interphase nuclei. We analyzed the three-dimensional organization of fibroblast and spermatocyte nuclei of the field mice carrying different number of B chromosomes using laser scanning microscopy and 3D fluorescence <i>in situ</i> hybridization...

BACKGROUND: We evaluated the effect of Saccharomyces boulardii CNCM I-745 on intestinal neuromuscular anomalies in an IBS-type mouse model of gastrointestinal motor dysfunctions elicited by Herpes Simplex Virus type 1 (HSV-1) exposure. METHODS: Mice were inoculated intranasally with HSV-1 (102 PFU) or vehicle at time 0 and 4 weeks later by the intragastric (IG) route (108 PFU). Six weeks after IG inoculum, mice were randomly allocated to receive oral gavage with either S...

Formation of secretary endometrial glands in the uterus known as adenogenesis is a typical process of branching morphogenesis involving dynamic epithelial growth and differentiation. Unsuccessful adenogenesis often leads to female infertility. However, it remains largely unexplored so far regarding the epigenetic machinery governing normal endometrial gland formation. Here, we demonstrated that PR-Set7, an epigenetic regulator for H4K20me1 modification, was extensively expressed in the postnatal uteri, and its conditional deletion resulted in a complete lack of endometrial glands and infertility in mice...

Perturbance in inflammatory pathways have been identified as one of the major factors which leads to neurodegenerative diseases (NDD). Owing to the limited access of human brain tissues and the immense complexity of the brain, animal models, specifically mouse models, play a key role in advancing the NDD field. However, many of these mouse models fail to reproduce the clinical manifestations and end points of the disease. NDD drugs, which passed the efficacy test in mice, were repeatedly not successful in clinical trials...

Alzheimer's disease (AD) is the most common form of dementia, characterized by progressive decline in cognitive abilities of the affected individuals. Biological markers are essential to identify individuals at early stages of the disease for timely therapeutic intervention. Currently, pathological biomarkers are detected either through cerebrospinal fluid analysis or brain imaging, or postmortem, all of which are expensive, invasive, or time consuming. Recently, some studies have shown that circulating miR-125b, miR-181c, miR-9, miR-191-5p, miR-26b-3p, and miR-28-3p may be biomarkers of AD...

Protein disulfide isomerase (PDI) is a chaperone protein located in the endoplasmic reticulum (ER). Nitric oxide-induced S-nitrosylation of PDI inhibits its enzymatic activity, leading to protein accumulation and activation of the unfolded protein response. Protein disulfide isomerase P5 (P5) is a member of the PDI family that mostly localizes to the ER lumen. Both S-nitrosylated PDI and S-nitrosylated P5 are found in Alzheimer's disease (AD) brain. Previously, we showed that expression of the ER stress marker, growth arrest, and DNA damage protein (GADD34) was significantly increased in neurons and oligodendrocytes in AD brain...

SCOPE: Extracts from olive (Olea europaea) leaves are used in Mediterranean traditional medicine as anti-inflammatory. They contain antioxidant phenolic compounds, like oleuropeoside, which could be interesting for the treatment of inflammatory conditions associated with oxidative stress in humans, including inflammatory bowel disease. METHODS AND RESULTS: The anti-inflammatory effects of olive leaf extract (0.5-25 mg/kg) were studied in two mice models of colitis (DSS and DNBS)...

Breast cancer is the most frequently diagnosed cancer in both more and less economically developed countries and remains the leading cause of cancer-related death in women worldwide. In this study, to explore the expression and pathological role of RSK4 in breast cancer progression, we demonstrated that RSK4 expression was significantly decreased in breast cancer cells and tissues, and the overexpression of RSK4 in MDA‑MB‑231 cells inhibited cell migration and invasion. In a mouse model experiment, overexpression of RSK4 in mice further confirmed its critical role in regulating breast cancer tumorigenicity...

Pidotimod is a synthetic dipeptide with biological and immuno‑modulatory properties. It has been widely used for treatment and prevention of recurrent respiratory infections. However, its impact on the regulation of allergic pulmonary inflammation is still not clear. In the current study, an ovalbumin (OVA)‑induced allergic asthma model was used to investigate the immune‑modulating effects of pidotimod on airway eosinophilia, mucus metaplasia and inflammatory factor expression compared with dexamethasone (positive control)...

Carrier-free nanodrugs formulated from the supramolecular self-assembly of pure drug molecules have emerged as an innovative and promising strategy for tumor therapy. We report herein a new and simple method to directly assemble a small hydrophobic anticancer drug, 10-hydroxycamptothecin (HCPT), with a photosensitizer chlorin e6 (Ce6) to form stable, discrete nanorods (NRs), which not only circumvent the extreme hydrophobicity of HCPT but also incorporate two different modalities into one delivery system for combination therapy...

BACKGROUND: Several proteins have been identified as potential diagnostic biomarkers in imaging, genetic, or proteomic studies in Alzheimer disease (AD) patients and mouse models. However, biomarkers for presymptom diagnosis of AD are still under investigation, as are the presymptom molecular changes in AD pathogenesis. OBJECTIVE: In this study, we aim to analyzed the early proteomic changes in APPSw,Ind mice and to conduct further functional studies on interesting proteins...

Fragile X syndrome (FXS) is the most frequently inherited form of intellectual disability and prevalent single-gene cause of autism. A priority of FXS research is to determine the molecular mechanisms underlying the cognitive and social functioning impairments in humans and the FXS mouse model. Glutamate ionotropic alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors (AMPARs) mediate a majority of fast excitatory neurotransmission in the central nervous system and are critically important for nearly all aspects of brain function, including neuronal development, synaptic plasticity, and learning and memory...

BACKGROUND: Cachexia is a complex metabolic and behavioural syndrome lacking effective therapies. Pancreatic ductal adenocarcinoma (PDAC) is one of the most important conditions associated with cachexia, with >80% of PDAC patients suffering from the condition. To establish the cardinal features of a murine model of PDAC-associated cachexia, we characterized the effects of implanting a pancreatic tumour cell line from a syngeneic C57BL/6 KRAS(G12D) P53(R172H) Pdx-Cre(+/+) (KPC) mouse...

Bone tissue engineering (BTE) holds promise for managing the clinical problem of large bone defects. However, clinical adoption of BTE is limited due to limited vascularization of constructs, which could be circumvented by pre-cultivation of osteogenic and endothelial derived cells in natural-based polymer scaffolds. However, until now not many studies compared the effect of mono- and cocultures pre-seeded in collagen before implantation. We utilized a mouse calvarial defect model and compared five groups of collagen scaffolds: a negative control of a collagen scaffold alone, a positive control treated with BMP-7, monocultures of either human osteoblasts (hOBs) or CD34+ cells, and a coculture of hOB and CD34(+) cells...

Craniosynostosis is commonly caused by mutations in fibroblast growth factor receptors, highlighting the essential role of FGF-mediated signalling in skeletal development. We set out to identify the molecular defect in a family referred for craniosynostosis and in whom no mutation was previously detected. Using Next-generation sequencing, we identified a novel missense mutation in FGF9. Modelling based upon the crystal structure and functional studies confirmed its pathogenicity showing that it impaired homodimerization and FGFR3 binding...

In this study, the potential effects of thalidomide (Thal) on bleomycin (BLM)-induced pulmonary fibrosis were investigated. BALB/C mice model of pulmonary fibrosis induced by an intratracheal instillation of BLM was adopted, and then was intraperitoneally injected with Thal (10, 20, 50 mg/kg) daily for 8 days, while the control and BLM-treated mouse groups were injected with a saline solution. The effects of Thal on pulmonary injury were evaluated by the lung wet/dry weight ratios and histopathological examination...

We present in this article a methodology for designing kinetic models of molecular signaling networks, which was exemplarily applied for modeling one of the Ras/MAPK signaling pathways in the mouse Y1 adrenocortical cell line. The methodology is interdisciplinary, that is, it was developed in a way that both dry and wet lab teams worked together along the whole modeling process.