International Journal of Experimental Pathology

Duchenne muscular dystrophy (DMD) occurs due to genetic mutations that lead to a deficiency in dystrophin production and consequent progressive degeneration of skeletal muscle fibres, through oxidative stress and an exacerbated inflammatory process. The flavonoid trilobatin (TLB) demonstrates antioxidant and anti-inflammatory potential. Its high safety profile and effective action make it a potent therapy for the process of dystrophic muscle myonecrosis. Thus, we sought to investigate the action of TLB on damage in a DMD model, the mdx mouse...

Transforming growth factor (TGF)-β and toll-like receptors (TLRs) have been shown to independently modulate the proliferation of hepatocellular carcinoma (HCC). Since a direct cross-talk between these two signalling pathways in HCC has not been clearly described before, we aimed here to explore the possibility of such interaction. A human HCC tissue array (n = 20 vs. four control samples), human HCC samples (n = 10) and steatohepatitis-driven murine HCC samples (control, NASH and HCC; n = 6/group) were immunostained for TGFβR1, pSMAD2, TRAF6, IRAK1 and PCNA...

Bone fractures are the most common form of musculoskeletal trauma worldwide. Numerous microRNAs (miRNAs) have been suggested to be participants in regulating bone-related diseases. Recent studies revealed the regulatory role of miR-22-3p in osteogenic differentiation, but its role in fracture healing has not been investigated previously. Here, a rat femoral fracture model was established, Bone marrow mesenchymal stem cells (BMSCs) were isolated to detect the specific function and underlying mechanisms of miR-22-3p...

Advanced glycation end-products (AGEs) are implicated in the pathogenesis of vascular disease. In previous studies we have found increased deposition of N(e)-(carboxymethyl)lysine (CML) in intramyocardial vasculature in the heart in acute myocardial infarction and myocarditis. It is known that the process of inflammation plays a role in the formation of AGEs. In this study we have explored the presence of CML (a major AGE) in the heart of patients with epicarditis using a monoclonal anti-CML antibody. Nine patients with epicarditis (n = 9) died and their hearts were used for this study, control were hearts from patients who died from conditions unrelated to heart disease and without signs of myocarditis or epicarditis CML deposition and complement were significantly increased in patients with epicarditis compared to control hearts...

Sepsis-induced acute lung injury (ALI) is an inflammatory condition involving the pyroptosis of macrophages. This study investigated the role of circular RNA hsa_circ_0006990 (circVAPA) in regulating macrophage pyroptosis in ALI and the underlying mechanisms. The expression pattern of circVAPA was examined in the mouse model of ALI and in the LPS-treated RAW264.7 macrophage cell line. Lung tissue damage was evaluated by haematoxylin and eosin staining, immunohistochemistry and a myeloperoxidase activity assay...

This study aimed to investigate the anti-inflammatory and wound healing effects of the polysaccharide extract from Opuntia ficus-indica cladodes (TPL-Ofi) using a rat cutaneous wound model. After anaesthesia, four 7-mm-diameter dorsal wounds per animal (n = 6/group for each experimental day of evaluation) were created in female Wistar rats using a surgical punch. The animals were treated topically twice daily with TPL-Ofi (0.01-1%; treated group) or sterile saline (control group) for a period of 21 days...

Diabetes mellitus is one of the most prevalent medical conditions, in both humans and animals. People with diabetes mellitus often experience slower than normal wound healing, making it a serious health concern. This study investigates the effect of M2 differentiated macrophages on full-thickness wound healing in white Westar rats exposed to streptozocin 70 mg/kg. A full-thickness skin defect with dimensions of 2 × 2 cm was created on the back of all the animals, and their blood sugar was simultaneously assessed...

Human bone marrow mesenchymal stem cells (hBMSCs) are attractive therapeutic agents for bone tissue regeneration owing to their osteogenic differentiation potential. Notoginsenoside R1 (NGR1) is a novel phytoestrogen with diverse pharmacological activities. Here, we probed whether NGR1 has an effect on the osteogenic differentiation of hBMSCs. EdU, CCK-8 and Transwell assays were used to measure proliferation and migration of hBMSCs after treatment with different doses of NGR1. hBMSCs were treated with osteogenic differentiation induction medium for osteogenesis...

This study aimed to investigate the effects of mitochondrial homeostasis on lipopolysaccharide (LPS)-induced endothelial cell barrier function and the mechanisms that underlie these effects. Cells were treated with LPS or oligomycin (mitochondrial adenosine triphosphate synthase inhibitor) and the mitochondrial morphology, mitochondrial reactive oxygen species (mtROS), and mitochondrial membrane potential (ΔΨm) were evaluated. Moreover, the shedding of glycocalyx-heparan sulphate (HS), the levels of HS-specific degrading enzyme heparanase (HPA), and the expression of occludin and zonula occludens (ZO-1) of Tight Junctions (TJ)s, which are mediated by myosin light chain phosphorylation (p-MLC), were assessed...

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Histomorphometric lung density measurements were used to evaluate the effects of Immulina on mouse pneumonia. Mice were intra-nasally exposed to H1N1 influenza virus at a dose of 5 × 104 PFU/50 μL/mouse. Lung density was measured using the NIH ImageJ software program. Density values were compared to semiquantitative pneumonia severity scores. Lung photomicrographs were evaluated at 25-×, 40-× and 400-× magnification. The study included viral inoculated controls (IC) and non-inoculated controls (NC) and mice either treated or not treated with Immulina...

Non-small cell lung cancer (NSCLC) imposes a significant economic burden on patients and society due to its low overall cure and survival rates. Tumour-associated macrophages (TAM) affect tumour development and may be a novel therapeutic target for cancer. We collected NSCLC and tumour-adjacent tissue samples. Compared with the tumour-adjacent tissues, the Activation Transcription Factor 3 (ATF3) and Colony Stimulating Factor 1 (CSF-1) were increased in NSCLC tissues. Levels of ATF3 and CSF-1 were identified in different cell lines (HBE, A549, SPC-A-1, NCI-H1299 and NCI-H1795)...

Porcine small intestinal submucosa, despite its successful use as a scaffold in regenerative medicine, has innate biomechanical heterogeneity. In this study, we hypothesized that human small intestinal submucosa could be a viable alternative bio-scaffold. For the first time, we characterize submucosal extraction from human small intestine and examine appropriate decellularization methods. In total, 16 human small intestinal submucosal samples were obtained and decellularized using three reported methods of porcine decellularization: Abraham, Badylak, and Luo...

Colorectal cancer, which is the third leading cause of cancer-related deaths worldwide, is a multistep disease, featuring preneoplastic aberrant crypt foci (ACF) as the early morphological manifestation. The roles of hemichannel-forming transmembrane Pannexin 1 (Panx1) protein have not been investigated in the context of colon carcinogenesis yet, although it has contrasting roles in other cancer types. Thus, this study was conducted to examine the effects of Panx1 knockout (Panx1-/- ) on the early events of chemically induced colon carcinogenesis in mouse...

Rare diseases collectively exact a high toll on society due to their sheer number and overall prevalence. Their heterogeneity, diversity, and nature pose daunting clinical challenges for both management and treatment. In this review, we discuss recent advances in clinical applications of gene therapy for rare diseases, focusing on a variety of viral and non-viral strategies. The use of adeno-associated virus (AAV) vectors is discussed in the context of Luxturna, licenced for the treatment of RPE65 deficiency in the retinal epithelium...

Neonatal hypoxic-ischaemic encephalopathy (HIE) refers to brain damage caused by intra-uterine distress and asphyxia/hypoxia during the perinatal and neonatal periods. MicroRNA (MiR)-214-3p plays a critical role in cell growth and apoptosis. The aim of this study was to investigate the expression and role of miR-214-3p in neonatal HIE development, and to explore the underlying mechanisms. The expression of miR-214-3p was significantly down-regulated, while that of Slc8a1, a direct target of miR-214-3p, was significantly up-regulated, in the brain tissue of neonatal HIE rats...

Recently macrophage polarization has emerged as playing an essential role in the oathogenesis of atherosclerosis, which is the most important underlying process in many types of cardiovascular diseases. Although Nek6 has been reported to be involved in various cellular processes, the effect of Nek6 on macrophage polarization remains unknown. Macrophages exposed to lipopolysaccharide (LPS) or IL-4 were used to establish an in vitro model for the study of regulation of classically (M1) or alternatively (M2) activated macrophage...

Experimental autoimmune encephalomyelitis (EAE) is a mouse model that can be used to investigate aetiology, pathogenesis, and treatment approaches for multiple sclerosis (MS). A novel integrated bioinformatics approach was used to understand the involvement of differentially expressed genes (DEGs) in the spleen of EAE mice through data mining of existing microarray and RNA-seq datasets. We screened differentially expressed mRNAs using mRNA expression profile data of EAE spleens taken from Gene Expression Omnibus (GEO)...

Haemangiomas (HAs) are prevalent vascular endothelial cell tumours. With respect to the possible involvement of HIF-1α in HAs, we have explored its role in haemangioma endothelial cell (HemEC) proliferation and apoptosis. shRNA HIF-1α and pcDNA3.1 HIF-α were manipulated into HemECs. HIF-α, VEGF, and VEGFR-2 mRNA and protein levels were assessed by qRT-PCR and Western blotting. Cell proliferation and viability, cell cycle and apoptosis, migration and invasion, and ability to form tubular structures were assessed by colony formation assay, CCK-8, flow cytometry, Transwell assay, and tube formation assay...

Human gastrointestinal tumours have been shown to contain massive numbers of tumour infiltrating regulatory T cells (Tregs), the presence of which are closely related to tumour immunity. This study was designed to develop new Treg-related prognostic biomarkers to monitor the prognosis of patients with gastric cancer (GC). Treg-related prognostic genes were screened from Treg-related differentially expressed genes in GC patients by using Cox regression analysis, based on which a prognostic model was constructed...