scholarly journals MicroRNAs in Animal Models of HCC

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1906 ◽  
Author(s):  
Francesca Fornari ◽  
Laura Gramantieri ◽  
Elisa Callegari ◽  
Ram C. Shankaraiah ◽  
Fabio Piscaglia ◽  
...  

Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related mortality. Molecular heterogeneity and absence of biomarkers for patient allocation to the best therapeutic option contribute to poor prognosis of advanced stages. Aberrant microRNA (miRNA) expression is associated with HCC development and progression and influences drug resistance. Therefore, miRNAs have been assayed as putative biomarkers and therapeutic targets. miRNA-based therapeutic approaches demonstrated safety profiles and antitumor efficacy in HCC animal models; nevertheless, caution should be used when transferring preclinical findings to the clinics, due to possible molecular inconsistency between animal models and the heterogeneous pattern of the human disease. In this context, models with defined genetic and molecular backgrounds might help to identify novel therapeutic options for specific HCC subgroups. In this review, we describe rodent models of HCC, emphasizing their representativeness with the human pathology and their usefulness as preclinical tools for assessing miRNA-based therapeutic strategies.

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Damir Hamamdzic ◽  
Robert L. Wilensky

Animal models of atherosclerosis have proven to be an invaluable asset in understanding the pathogenesis of the disease. However, large animal models may be needed in order to assess novel therapeutic approaches to the treatment of atherosclerosis. Porcine models of coronary and peripheral atherosclerosis offer several advantages over rodent models, including similar anatomical size to humans, as well as genetic expression and development of high-risk atherosclerotic lesions which are similar to humans. Here we review the four models of porcine atherosclerosis, including the diabetic/hypercholesterolemic model, Rapacz-familial hypercholesterolemia pig, the (PCSK9) gain-of-function mutant pig model, and the Ossabaw miniature pig model of metabolic syndrome. All four models reliably represent features of human vascular disease.


2021 ◽  
Vol 8 ◽  
Author(s):  
Claudia Richter ◽  
Rabea Hinkel

Diabetes and the often accompanying cardiovascular diseases including cardiomyopathy represent a complex disease, that is reluctant to reveal the molecular mechanisms and underlying cellular responses. Current research projects on diabetic cardiomyopathy are predominantly based on animal models, in which there are not only obvious advantages, such as genetics that can be traced over generations and the directly measurable influence of dietary types, but also not despisable disadvantages. Thus, many studies are built up on transgenic rodent models, which are partly comparable to symptoms in humans due to their genetic alterations, but on the other hand are also under discussion regarding their clinical relevance in the translation of biomedical therapeutic approaches. Furthermore, a focus on transgenic rodent models ignores spontaneously occurring diabetes in larger mammals (such as dogs or pigs), which represent with their anatomical similarity to humans regarding their cardiovascular situation appealing models for testing translational approaches. With this in mind, we aim to shed light on the currently most popular animal models for diabetic cardiomyopathy and, by weighing the advantages and disadvantages, provide decision support for future animal experimental work in the field, hence advancing the biomedical translation of promising approaches into clinical application.


2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Keya Li ◽  
Xinyue Li ◽  
Guiying Shi ◽  
Xuepei Lei ◽  
Yiying Huang ◽  
...  

AbstractAnimal models provide an opportunity to assess the optimal treatment way and the underlying mechanisms of direct clinical application of adipose-derived stem cells (ADSCs). Previous studies have evaluated the effects of primitive and induced ADSCs in animal models of Parkinson’s disease (PD). Here, eight databases were systematically searched for studies on the effects and in vivo changes caused by ADSC intervention. Quality assessment was conducted using a 10-item risk of bias tool. For the subsequent meta-analysis, study characteristics were extracted and effect sizes were computed. Ten out of 2324 published articles (n = 169 animals) were selected for further meta-analysis. After ADSC therapy, the rotation behavior (10 experiments, n = 156 animals) and rotarod performance (3 experiments, n = 54 animals) were improved (P < 0.000 01 and P = 0.000 3, respectively). The rotation behavior test reflected functional recovery, which may be due to the neurogenesis from neuronally differentiated ADSCs, resulting in a higher pooled effect size of standard mean difference (SMD) (− 2.59; 95% CI, − 3.57 to − 1.61) when compared to that of primitive cells (− 2.18; 95% CI, − 3.29 to − 1.07). Stratified analyses by different time intervals indicated that ADSC intervention exhibited a long-term effect. Following the transplantation of ADSCs, tyrosine hydroxylase-positive neurons recovered in the lesion area with pooled SMD of 13.36 [6.85, 19.86]. Transplantation of ADSCs is a therapeutic option that shows long-lasting effects in animal models of PD. The potential mechanisms of ADSCs involve neurogenesis and neuroprotective effects. The standardized induction of neural form of transplanted ADSCs can lead to a future application in clinical practice.


2010 ◽  
Vol 2 (1) ◽  
pp. 17-25 ◽  
Author(s):  
Opeolu Adeoye ◽  
Joseph F. Clark ◽  
Pooja Khatri ◽  
Kenneth R. Wagner ◽  
Mario Zuccarello ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Yang-wei Wang ◽  
Guang-dong Sun ◽  
Jing Sun ◽  
Shu-jun Liu ◽  
Ji Wang ◽  
...  

Diabetes mellitus, especially type 2 diabetes (T2DM), is one of the most common chronic diseases and continues to increase in numbers with large proportion of health care budget being used. Many animal models have been established in order to investigate the mechanisms and pathophysiologic progress of T2DM and find effective treatments for its complications. On the basis of their strains, features, advantages, and disadvantages, various types of animal models of T2DM can be divided into spontaneously diabetic models, artificially induced diabetic models, and transgenic/knockout diabetic models. Among these models, the spontaneous rodent models are used more frequently because many of them can closely describe the characteristic features of T2DM, especially obesity and insulin resistance. In this paper, we aim to investigate the current available spontaneous rodent models for T2DM with regard to their characteristic features, advantages, and disadvantages, and especially to describe appropriate selection and usefulness of different spontaneous rodent models in testing of various new antidiabetic drugs for the treatment of type 2 diabetes.


2016 ◽  
Vol 34 (4) ◽  
pp. 347-355 ◽  
Author(s):  
M. Omar Farooq ◽  
Ramon Bataller

Alcoholic liver disease (ALD) is a leading cause of liver-related morbidity and mortality. ALD encompasses a spectrum of disorders ranging from asymptomatic steatosis, alcoholic steatohepatitis, fibrosis, cirrhosis and its related complications. Moreover, patients can develop an acute-on-chronic form of liver failure called alcoholic hepatitis (AH). Most patients are diagnosed at advanced stages of the disease with higher rates of complications and mortality. The mainstream of therapy of ALD patients, regardless of the disease stage, is prolonged alcohol abstinence. The current therapeutic regimens for AH (i.e. prednisolone) have limited efficacy and targeted therapies are urgently needed. The development of such therapies requires translational studies in human samples and suitable animal models that reproduce clinical and histological features of AH. In recent years, new animal models that simulate some of the features of human AH have been developed, and translational studies using human samples have identified potential pathogenic factors and histological parameters that predict survival. In this review, we discuss the pathogenesis and management of ALD, focusing on AH, its current therapies and potential treatment targets.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Diana L Diesen ◽  
Jonathan S Stamler

Transfusion of stored red blood cells (RBCs) is associated with a decrease in tissue oxygenation in animal models and with increased mortality and morbidity in patients. Recent studies have demonstrated that stored RBCs are deficient in vasodilatory ability and depleted of S -nitrosohemoglobin (SNO-Hb), and that renitrosylation ex vivo can increase SNO-Hb levels and restore vasoactivity. We have examined in a mouse model the extent to which transfusion impairs tissue oxygenation and whether SNO-Hb repletion can ameliorate that impairment. We report here that transfusion of (mouse) RBCs stored for 1 day or 1 week results in tissue hypoxia that is largely prevented by SNO-Hb repletion prior to transfusion ( 1 day stored blood : % decrease in oxygenation 58+/−10% untreated vs. 92+/−0.7% SNO-Hb repleted, p<0.05, n=3– 6; 1 week stored blood : % decrease in oxygenation 66+/−10% untreated vs. 91+/−2.8% SNO-Hb repleted, p<0.05, n=3– 6). Storage of mouse blood beyond human expiration-equivalents (1 month) resulted in substantial lysis and the death of all mice transfused (native and SNO-Hb repleted blood, n=5). In conclusion, repletion of SNO-Hb ameliorates the decrease in tissue oxygenation that results from transfusion of untreated stored blood. Therefore, SNO-Hb repletion may provide a simple and efficacious method to reduce transfusion-related mortality and morbidity.


2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Kyota Fujita ◽  
Yusaku Nakabeppu ◽  
Mami Noda

Since the first description of Parkinson's disease (PD) nearly two centuries ago, a number of studies have revealed the clinical symptoms, pathology, and therapeutic approaches to overcome this intractable neurodegenerative disease. 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) are neurotoxins which produce Parkinsonian pathology. From the animal studies using these neurotoxins, it has become well established that oxidative stress is a primary cause of, and essential for, cellular apoptosis in dopaminergic neurons. Here, we describe the mechanism whereby oxidative stress evokes irreversible cell death, and propose a novel therapeutic strategy for PD using molecular hydrogen. Hydrogen has an ability to reduce oxidative damage and ameliorate the loss of nigrostriatal dopaminergic neuronal pathway in two experimental animal models. Thus, it is strongly suggested that hydrogen might provide a great advantage to prevent or minimize the onset and progression of PD.


2010 ◽  
Vol 2010 ◽  
pp. 1-11 ◽  
Author(s):  
Reema Zeineldin ◽  
Carolyn Y. Muller ◽  
M. Sharon Stack ◽  
Laurie G. Hudson

Ovarian carcinoma is the leading cause of death from gynecologic malignancy in the US. Factors such as the molecular heterogeneity of ovarian tumors and frequent diagnosis at advanced stages hamper effective disease treatment. There is growing emphasis on the identification and development of targeted therapies to disrupt molecular pathways in cancer. The epidermal growth factor (EGF) receptor is one such protein target with potential utility in the management of ovarian cancer. This paper will discuss contributions of EGF receptor activation to ovarian cancer pathogenesis and the status of EGF receptor inhibitors and EGF receptor targeted therapies in ovarian cancer treatment.


Author(s):  
Haruhiko Fujihira ◽  
Makoto Asahina ◽  
Tadashi Suzuki

Summary Cytosolic peptide:N-glycanase (NGLY1) is an enzyme that cleaves N-glycans from glycoproteins that has been retrotranslocated from the endoplasmic reticulum (ER) lumen into the cytosol. It is known that NGLY1 is involved in the degradation of cytosolic glycans (non-lysosomal glycan degradation) as well as ER-associated degradation (ERAD), a quality control system for newly synthesized glycoproteins. The discovery of NGLY1 deficiency, which is caused by mutations in the human NGLY1 gene and results in multisystemic symptoms, has attracted interest in the physiological functions of NGLY1 in mammals. Studies using various animal models led to the identification of possible factors that contribute to the pathogenesis of NGLY1 deficiency. In this review, we summarize phenotypic consequences that have been reported for various Ngly1-deficient rodent models, and discuss future perspectives to provide more insights into the physiological functions of NGLY1.


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