The CXC chemokine receptor 4 (CXCR4) in endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) is crucial for vascular integrity. The atheroprotective functions of CXCR4 in vascular cells may be counteracted by atherogenic functions in other nonvascular cell types. Thus, strategies for cell-specifically augmenting CXCR4 function in vascular cells are crucial if this receptor is to be useful as a therapeutic target in treating atherosclerosis and other vascular disorders.
View Article and Find Full Text PDFThe mRNA expression of the dipeptidyl peptidase 4 (DPP4) gene family is highly upregulated in human hepatocellular carcinoma (HCC) and is associated with poor survival in HCC patients. Compounds that inhibit the DPP4 enzyme family, such as talabostat and ARI-4175, can mediate tumour regression by immune-mediated mechanisms that are believed to include NLRP1 activation. This study investigated the expression and activity of the DPP4 family during the development of HCC and evaluated the efficacy of ARI-4175 in the treatment of early HCC in mice.
View Article and Find Full Text PDFAtherosclerosis is a chronic inflammatory disease of the arterial vessel wall and underlies the development of cardiovascular diseases, such as myocardial infarction and ischemic stroke. As such, atherosclerosis stands as the leading cause of death and disability worldwide and intensive scientific efforts are made to investigate its complex pathophysiology, which involves the deregulation of crucial intracellular pathways and intricate interactions between diverse cell types. A growing body of evidence, including in vitro and in vivo studies involving cell-specific deletion of autophagy-related genes (ATGs), has unveiled the mechanistic relevance of cell-specific (endothelial, smooth-muscle, and myeloid cells) defective autophagy in the processes of atherogenesis.
View Article and Find Full Text PDFHepatocellular carcinoma (HCC) represents ~90% of all cases of primary liver cancer and occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Establishing appropriate animal models for HCC is required for basic and translational studies, especially the models that can recapitulate one of the human disease settings. Current animal models can be categorized as chemically-induced, genetically-engineered, xenograft, or a combination of these with each other or with a metabolic insult.
View Article and Find Full Text PDFThe occurrence of a spontaneous nephropathy with intranuclear inclusions in laboratory mice has puzzled pathologists for over 4 decades, because its etiology remains elusive. The condition is more severe in immunodeficient animals, suggesting an infectious cause. Using metagenomics, we identify the causative agent as an atypical virus, termed "mouse kidney parvovirus" (MKPV), belonging to a divergent genus of Parvoviridae.
View Article and Find Full Text PDFThe urgent unmet need for hepatocellular carcinoma (HCC) therapies is addressed here by characterising a novel mouse model of HCC in the context of ongoing liver damage and overnutrition. Male C57Bl/6J mice were treated with diethylnitrosamine (DEN) and thioacetamide (TAA), and some were provided with an atherogenic high fat diet (HFD). Inflammation, steatosis, fibrosis, 87 genes, liver lesions and intratumoural leukocyte subsets were quantified up to 24 weeks of age.
View Article and Find Full Text PDFPrimary liver cancer is the second most common cause of mortality from cancer. The most common models of hepatocellular carcinoma, which use a chemical and/or metabolic insult, xenograft, or genetic manipulation, are discussed in this review. In the tumour microenvironment lymphocytes, fibroblasts, endothelial cells and antigen presenting cells are important determinants of cell fate.
View Article and Find Full Text PDFFemale Pelvic Med Reconstr Surg
July 2013
Objectives: Tissue interposition is an important part of vesicovaginal fistula (VVF) repair that has been shown to improve success rates. The most common interpositional flap used during a transabdominal VVF repair is the omental flap; however, in some cases, it cannot be used. The urachus is a well-vascularized tissue that is easily mobilized for interposition.
View Article and Find Full Text PDFObjective: To determine the proportion of patients with rheumatoid arthritis (RA) under rheumatologic care treated with disease-modifying antirheumatic drugs (DMARD) within 6 months from symptom onset and the components of time to treatment and its predictors.
Methods: A historical inception cohort of 339 patients with RA randomly selected from 18 rheumatology practices was audited. The proportion that initiated DMARD treatment within 6 months from symptom onset was estimated using Kaplan-Meier analysis.
Objective: To describe early rheumatologic management for newly diagnosed rheumatoid arthritis (RA) in Canada.
Methods: A retrospective cohort of 339 randomly selected patients with RA diagnosed from 2001-2003 from 18 rheumatology practices was audited between 2005-2007.
Results: The most frequent initial disease-modifying antirheumatic drugs (DMARD) included hydroxychloroquine (55.
Dermatologic secondary procedures involve careful preoperative planning and patient preparation, skillful execution of the appropriate procedure, and thorough postoperative wound care. Many modalities of treatment are used, including skin preparation through elimination of inflammatory conditions, resurfacing of skin, and improvement of patient health. Proper selection of incisional design, local or regional flaps, and grafting techniques is key to successful revisional surgery.
View Article and Find Full Text PDFJ Oral Maxillofac Surg
September 2006
Purpose: Nearly 40% of all-terrain vehicle (ATV) crash-related fatalities involve pediatric patients, with many of these patients dying from head and neck injuries. West Virginia is in a unique position to examine these injuries because of its high rate of ATV use. This study examines craniofacial ATV-related trauma in children.
View Article and Find Full Text PDF