Animal Models of Human Pathology: Revision, Relevance and Refinements.

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Selection and Evaluation of mRNA and miRNA Reference Genes for Expression Studies (qPCR) in Archived Formalin-Fixed and Paraffin-Embedded (FFPE) Colon Samples of DSS-Induced Colitis Mouse Model.

The choice of appropriate reference genes is essential for correctly interpreting qPCR data and results. However, the majority of animal studies use a single reference gene without any prior evaluation. Therefore, many qPCR results from rodent studies can be misleading, affecting not only reproducibility but also translatability.

Molecular and Cellular Markers in Chlorhexidine-Induced Peritoneal Fibrosis in Mice.

Understanding the tissue changes and molecular mechanisms of preclinical models is essential for creating an optimal experimental design for credible translation into clinics. In our study, a chlorhexidine (CHX)-induced mouse model of peritoneal fibrosis was used to analyze histological and molecular/cellular alterations induced by 1 and 3 weeks of intraperitoneal CHX application. CHX treatment for 1 week already caused injury, degradation, and loss of mesothelial cells, resulting in local inflammation, with the most severe structural changes occurring in the peritoneum around the ventral parts of the abdominal wall.

Cobalt Ferrite Magnetic Nanoparticles for Tracing Mesenchymal Stem Cells in Tissue: A Preliminary Study.

Therapy with mesenchymal stem cells (MSCs) is promising in many diseases. Evaluation of their efficacy depends on adequate follow-up of MSCs after transplantation. Several studies have shown that MSCs can be labeled and subsequently visualized with magnetic nanoparticles (NPs).

Hyperspectral evaluation of vasculature in induced peritonitis mouse models.

Imaging of blood vessel structure in combination with functional information about blood oxygenation can be important in characterizing many different health conditions in which the growth of new vessels contributes to the overall condition. In this paper, we present a method for extracting comprehensive maps of the vasculature from hyperspectral images that include tissue and vascular oxygenation. We also show results from a preclinical study of peritonitis in mice.

Cisplatin Mouse Models: Treatment, Toxicity and Translatability.

Cisplatin is one of the most widely used chemotherapeutic drugs in the treatment of a wide range of pediatric and adult malignances. However, it has various side effects which limit its use. Cisplatin mouse models are widely used in studies investigating cisplatin therapeutic and toxic effects.

Exploring the role of the complement system, endothelial injury, and microRNAs in thrombotic microangiopathy after kidney transplantation.

Objective: We investigated whether the recipient's complement system function, kidney graft endothelial ultrastructural injury, and microRNA (miRNA) expression before transplantation may be associated with the risk of posttransplant thrombotic microangiopathy (TMA).

Methods: Complement system function assessment, histological and ultrastructural examination of preimplantation and kidney graft biopsies, and microRNA assessment were performed on kidney transplant recipients (KTRs) with TMA.

Results: On the basis of the clinical course, histological findings, and miRNA patterns, the following two TMA phenotypes were observed: a self-limiting disease that was localized to the kidney graft and a systemic disease that progressed to graft failure without timely treatment.

Chronic Disruption of the Late Cholesterol Synthesis Leads to Female-Prevalent Liver Cancer.

While the role of cholesterol in liver carcinogenesis remains controversial, hepatocellular carcinoma generally prevails in males. Herein, we uncover pathways of female-prevalent progression to hepatocellular carcinoma due to chronic repression of cholesterogenic lanosterol 14α-demethylase (CYP51) in hepatocytes. Tumors develop in knock-out mice after year one, with 2:1 prevalence in females.

Hyperspectral evaluation of peritoneal fibrosis in mouse models.

Analysis of morphological changes of the peritoneal membrane is an essential part of animal studies when investigating molecular mechanisms involved in the development of peritoneal fibrosis or testing the effects of potential therapeutic agents. Current methods, such as histology and immunohistochemistry, require time consuming sample processing and analysis and result in limited spatial information. In this paper we present a new method to evaluate structural and chemical changes in an animal model of peritoneal fibrosis that is based on hyperspectral imaging and a model of light transport.

Diagnostic and treatment challenge of unrecognized subacute bacterial endocarditis associated with ANCA-PR3 positive immunocomplex glomerulonephritis: a case report and literature review.

Background: Diagnosis and treatment of either ANCA disease or silent infection-related glomerulonephritis is complicated and is a huge treatment challenge when overlapping clinical manifestations occur. We report a case of ANCA-PR3 glomerulonephritis, nervous system involvement, hepatosplenomegaly and clinically silent subacute infectious endocarditis.

Case Presentation: A 57-year-old man with known mitral valve prolaps was admitted for unexplained renal failure with signs of nephritic syndrome, hepatosplenomegaly, sudden unilateral hearing loss, vertigo, malaise, new onset hemolytic anemia and thrombocytopenia.

The Role of IgA in the Pathogenesis of IgA Nephropathy.

Immunoglobulin A (IgA) is the most abundant antibody isotype produced in humans, predominantly present in the mucosal areas where its main functions are the neutralization of toxins, prevention of microbial invasion across the mucosal epithelial barrier, and simultaneous maintenance of a physiologically indispensable symbiotic relationship with commensal bacteria. The process of IgA biosynthesis, interaction with receptors, and clearance can be disrupted in certain pathologies, like IgA nephropathy, which is the most common form of glomerulonephritis worldwide. This review summarizes the latest findings in the complex characteristics of the molecular structure and biological functions of IgA antibodies, offering an in-depth overview of recent advances in the understanding of biochemical, immunologic, and genetic factors important in the pathogenesis of IgA nephropathy.

Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges.

Cisplatin is an antitumor drug used in the treatment of a wide variety of malignancies. However, its primary dose-limiting side effect is kidney injury, which is a major clinical concern. To help understand mechanisms involved in the development of kidney injury, cisplatin rodent model has been developed.

Early Graft Loss after Kidney Transplantation: Endothelial Dysfunction of Renal Microvasculature.

Decision process about the acceptance of the deceased donor kidney for transplantation might be challenging. Although histological evaluation of pretransplant donor kidney biopsy provides reliable information regarding cortical necrosis, vascular thrombosis, extensive global glomerulosclerosis, and interstitial fibrosis/tubular atrophy, only electron microscopy enables thorough and reliable insights into microvasculature changes of kidney graft. The aim of the present paper is to briefly present two cases of early kidney graft loss.

Effect of high-fat mixed lipid diet and swimming on fibre types in skeletal muscles of rats with colon tumours.

Skeletal muscle fibre types, whose characteristics are determined by myosin heavy chain (MyHC) isoforms, can adapt to changed physiological demands with changed MyHC isoform expression resulting in the fibre type transitions. The endurance training is known to induce fast-to-slow transitions and has beneficial effect in carcinogenesis, whereas the effect of an excessive fat intake and its interaction with the effect of swimming are less conclusive. Therefore, we studied the effect of high-fat mixed lipid (HFML) diet and long-term (21-week) swimming on fibre type transitions and their average diameters by immunohistochemical demonstration of MyHC isoforms in slow soleus (SOL), fast extensor digitorum longus (EDL), and mixed gastrocnemius medialis and lateralis (GM, GL) muscles, divided to deep and superficial portions (GMd, GMs, GLd, GLs), of sedentary and swimming Wistar rats with experimentally (dimethylhydrazine) induced colon tumours and fed either with HFML or low-fat corn oil (LFCO) diet.

(Mesenchymal) Stem Cell-Based Therapy in Cisplatin-Induced Acute Kidney Injury Animal Model: Risk of Immunogenicity and Tumorigenicity.

Pathogenesis of AKI is complex and involves both local events in the kidney as well as systemic effects in the body that are interconnected and interdependent. Despite intensive investigations there is still no pharmacological agent that could provide complete protection against cisplatin nephrotoxicity. In the last decade mesenchymal stem cells (MSCs) have been proposed as a potentially useful therapeutic strategy in various diseases, including acute kidney injury.

Effect of carcinogen 1,2-dimethylhydrazine treatment on fiber types in skeletal muscles of male Wistar rats.

The cancerogen 1,2-dimethylhydrazine (DMH), widely used in the experimental animal model of carcinogenesis, affects various organs, but its effect on muscle fibers is unknown. To evaluate the effect of 15-week DMH treatment on the fiber size and myosin heavy chain (MyHC) isoforms, which substantially determine fiber types and their contractile characteristics, pure and hybrid fiber types were immunohistochemically determined according to the MyHC isoform expression in soleus, extensor digitorum longus, gastrocnemius medialis and lateralis muscles of DMH-treated and control male Wistar rats. Whereas the size of fibers was mostly unaffected, the MyHC isoform expression was partially affected in both gastrocnemius samples, but not in the soleus and extensor digitorum longus of DMH-treated rats.

Cardiac autonomic modulation induced by doxorubicin in a rodent model of colorectal cancer and the influence of fullerenol pretreatment.

The very effective anticancer drug doxorubicin (DOX) is known to have cardiotoxic side effects, which could be accompanied by autonomic modulation. Autonomic disbalance might even be an initiating mechanism underlying DOX-induced cardiotoxicity and can be studied noninvasively by the analysis of heart rate variability (HRV). A number of strategies have been assessed to predict chemotherapy-induced cardiac dysfunction while HRV, a potential detecting tool, has not yet been tested.

Disrupting Hepatocyte Cyp51 from Cholesterol Synthesis Leads to Progressive Liver Injury in the Developing Mouse and Decreases RORC Signalling.

Development of mice with hepatocyte knockout of lanosterol 14α-demethylase (H) from cholesterol synthesis is characterized by the progressive onset of liver injury with ductular reaction and fibrosis. These changes begin during puberty and are generally more aggravated in the knockout females. However, a subgroup of (pre)pubertal knockout mice (runts) exhibits a pronounced male prevalent liver dysfunction characterized by downregulated amino acid metabolism and elevated Casp12.

Dextran sulphate sodium colitis in C57BL/6J mice is alleviated by Lactococcus lactis and worsened by the neutralization of Tumor necrosis Factor α.

TNFα has a well-established role in inflammatory bowel disease that affects the gastrointestinal tract and is usually manifested as Crohn's disease or ulcerative colitis. We have compared Lactococcus lactis NZ9000 displaying TNFα-binding affibody with control Lactococcus lactis and with anti-TNFα antibody infliximab for the treatment of mice with dextran sulphate sodium (DSS)-induced colitis. L.

Cytochrome P450 metabolism of the post-lanosterol intermediates explains enigmas of cholesterol synthesis.

Cholesterol synthesis is among the oldest metabolic pathways, consisting of the Bloch and Kandutch-Russell branches. Following lanosterol, sterols of both branches are proposed to be dedicated to cholesterol. We challenge this dogma by mathematical modeling and with experimental evidence.

Improved Protective Effect of Umbilical Cord Stem Cell Transplantation on Cisplatin-Induced Kidney Injury in Mice Pretreated with Antithymocyte Globulin.

Mesenchymal stem cells (MSCs) are recognised as a promising tool to improve renal recovery in experimental models of cisplatin-induced acute kidney injury. However, these preclinical studies were performed on severely immunodeficient animals. Here, we investigated whether human umbilical cord derived MSC treatment could equally ameliorate acute kidney injury induced by cisplatin and prolong survival in mice with a normal immune system and those with a suppressed immune system by polyclonal antithymocyte globulin (ATG).

Lessons from hepatocyte-specific Cyp51 knockout mice: impaired cholesterol synthesis leads to oval cell-driven liver injury.

We demonstrate unequivocally that defective cholesterol synthesis is an independent determinant of liver inflammation and fibrosis. We prepared a mouse hepatocyte-specific knockout (LKO) of lanosterol 14α-demethylase (CYP51) from the part of cholesterol synthesis that is already committed to cholesterol. LKO mice developed hepatomegaly with oval cell proliferation, fibrosis and inflammation, but without steatosis.

Hidden disease susceptibility and sexual dimorphism in the heterozygous knockout of Cyp51 from cholesterol synthesis.

We examined the genotype-phenotype interactions of Cyp51+/- mice carrying one functional allele of lanosterol 14α-demethylase from cholesterol biosynthesis. No distinct developmental or morphological abnormalities were observed by routine visual inspection of Cyp51+/- and Cyp51+/+ mice and fertility was similar. We further collected a large data-set from female and male Cyp51+/- mice and controls fed for 16 weeks with three diets and applied linear regression modeling.

Sex differences in the hepatic cholesterol sensing mechanisms in mice.

Cholesterol is linked to many multifactorial disorders, including different forms of liver disease where development and severity depend on the sex. We performed a detailed analysis of cholesterol and bile acid synthesis pathways at the level of genes and metabolites combined with the expression studies of hepatic cholesterol uptake and transport in female and male mice fed with a high-fat diet with or without cholesterol. Lack of dietary cholesterol led to a stronger response of the sterol sensing mechanism in females, resulting in higher expression of cholesterogenic genes compared to males.