ING function in apoptosis in diverse model systemsThis paper is one of a selection of papers published in this Special Issue, entitled CSBMCB’s 51st Annual Meeting – Epigenetics and Chromatin Dynamics, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 87 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Sitar Shah ◽  
Heather Smith ◽  
Xiaolan Feng ◽  
Derrick E. Rancourt ◽  
Karl Riabowol

Genetic studies in model organisms have shown that programmed cell death (apoptosis) plays a significant role during development, where a deficiency in apoptosis results in severe and diverse diseases. Dysregulation of apoptosis also contributes to a variety of human diseases, such as cancer and autoimmune diseases. ING family proteins (ING1–ING5) are involved in many cellular processes, and appear to play a significant role in apoptosis. Loss or downregulation of ING protein function is frequently observed in different tumour types, many of which are resistant to apoptosis, thus warranting their classification as type II tumour suppressors. Several different in vitro and in vivo models have explored the role of ING proteins in regulating apoptosis. In this review, we discuss the progress that has been made in understanding ING protein function in apoptosis using in vitro studies and Mus musculus, Xenopus laevis, and Caenorhabditis elegans experimental models, with an emphasis on ING1 and ING3.

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 460
Author(s):  
Beatriz Medeiros-Fonseca ◽  
Antonio Cubilla ◽  
Haissa Brito ◽  
Tânia Martins ◽  
Rui Medeiros ◽  
...  

Penile cancer is an uncommon malignancy that occurs most frequently in developing countries. Two pathways for penile carcinogenesis are currently recognized: one driven by human papillomavirus (HPV) infection and another HPV-independent route, associated with chronic inflammation. Progress on the clinical management of this disease has been slow, partly due to the lack of preclinical models for translational research. However, exciting recent developments are changing this landscape, with new in vitro and in vivo models becoming available. These include mouse models for HPV+ and HPV− penile cancer and multiple cell lines representing HPV− lesions. The present review addresses these new advances, summarizing available models, comparing their characteristics and potential uses and discussing areas that require further improvement. Recent breakthroughs achieved using these models are also discussed, particularly those developments pertaining to HPV-driven cancer. Two key aspects that still require improvement are the establishment of cell lines that can represent HPV+ penile carcinomas and the development of mouse models to study metastatic disease. Overall, the growing array of in vitro and in vivo models for penile cancer provides new and useful tools for researchers in the field and is expected to accelerate pre-clinical research on this disease.


2020 ◽  
Vol 21 (13) ◽  
pp. 4627
Author(s):  
Olivia Rastoin ◽  
Gilles Pagès ◽  
Maeva Dufies

Neovascular age-related macular degeneration (vAMD), characterized by the neo-vascularization of the retro-foveolar choroid, leads to blindness within few years. This disease depends on angiogenesis mediated by the vascular endothelial growth factor A (VEGF) and to inflammation. The only available treatments consist of monthly intravitreal injections of antibodies directed against VEGF or VEGF/VEGFB/PlGF decoy receptors. Despite their relative efficacy, these drugs only delay progression to blindness and 30% of the patients are insensitive to these treatments. Hence, new therapeutic strategies are urgently needed. Experimental models of vAMD are essential to screen different innovative therapeutics. The currently used in vitro and in vivo models in ophthalmic translational research and their relevance are discussed in this review.


Author(s):  
Verônica Assalin Zorgetto-Pinheiro ◽  
Alexandre Meira de Vasconcelos ◽  
Rafael Sanaiotte Pinheiro ◽  
Danielle Bogo ◽  
Iandara Schettert Silva

Rheumatoid arthritis is an autoimmune and chronic pathological condition characterized by an inflammatory process of the joints It is a complex and multifactorial, involving genetic, epigenetic and environmental factors and the use of experimental models is required to better understand its pathology and for drug testing. The aim of this study was to perform a systematic literature review on experimental models in rheumatoid arthritis using IRAMUTEQ, a software that analysis, qualitatively and quantitatively, text fragments, as a methodological tool. After searching for articles published in the last five years on Scopus database and applying the exclusion criteria, we ended with 84 articles. The most commonly employed experimental models was the arthritis induction by inoculation of the Complete Freund's Adjuvant (CFA), followed by the use of combined methodologies and the collagen-induced arthritis (CIA). The analyses of abstracts by the IRAMUTEQ software provided a classification according to their textual elements in four classes, which were grouped into three main themes: in vivo models (class 1), clinical practice and traditional medicine (classes 2 and 3) and in vitro models (class 4) and it was also possible to build a similarity tree of the terms present in the abstracts and a word cloud with the most cited terms. Thus, the use of the IRAMUTEQ software as a methodological tool has been satisfactory, since it was possible to identify the main experimental models used, keywords, pathological processes and molecules involved in the pathogenesis of rheumatoid arthritis free of the researchers’ bias, in addition to being a tool for visual and intuitive results.


Cancers ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1677 ◽  
Author(s):  
Jose J. G. Marin ◽  
Elisa Herraez ◽  
Elisa Lozano ◽  
Rocio I. R. Macias ◽  
Oscar Briz

The lack of response to pharmacological treatment constitutes a substantial limitation in the handling of patients with primary liver cancers (PLCs). The existence of active mechanisms of chemoresistance (MOCs) in hepatocellular carcinoma, cholangiocarcinoma, and hepatoblastoma hampers the usefulness of chemotherapy. A better understanding of MOCs is needed to develop strategies able to overcome drug refractoriness in PLCs. With this aim, several experimental models are commonly used. These include in vitro cell-free assays using subcellular systems; studies with primary cell cultures; cancer cell lines or heterologous expression systems; multicellular models, such as spheroids and organoids; and a variety of in vivo models in rodents, such as subcutaneous and orthotopic tumor xenografts or chemically or genetically induced liver carcinogenesis. Novel methods to perform programmed genomic edition and more efficient techniques to isolate circulating microvesicles offer new opportunities for establishing useful experimental tools for understanding the resistance to chemotherapy in PLCs. In the present review, using three criteria for information organization: (1) level of research; (2) type of MOC; and (3) type of PLC, we have summarized the advantages and limitations of the armamentarium available in the field of pharmacological investigation of PLC chemoresistance.


Author(s):  
Maritza Torres ◽  
Hans De Cock ◽  
Adriana Marcela Celis Ramírez

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated in the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interaction of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review we present different models that have been implemented in the fungal infections study with greater attention in Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host-microbe interactions. This is due to the fact that these systems have shown to have reliable results, which correlate with those obtained from mammalian models. Example of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.


2009 ◽  
Vol 87 (1) ◽  
pp. 265-272 ◽  
Author(s):  
Ling Zhang ◽  
Kristi Jones ◽  
Feng Gong

The assembly of DNA into chromatin in eukaryotic cells affects all DNA-related cellular activities, such as replication, transcription, recombination, and repair. Rearrangement of chromatin structure during nucleotide excision repair (NER) was discovered more than 2 decades ago. However, the molecular basis of chromatin dynamics during NER remains undefined. Pioneering studies in the field of gene transcription have shown that ATP-dependent chromatin-remodeling complexes and histone-modifying enzymes play a critical role in chromatin dynamics during transcription. Similarly, recent studies have demonstrated that the SWI/SNF chromatin-remodeling complex facilitates NER both in vitro and in vivo. Additionally, histone acetylation has also been linked to the NER of ultraviolet light damage. In this article, we will discuss the role of these identified chromatin-modifying activities in NER.


2020 ◽  
Vol 6 (3) ◽  
pp. 155
Author(s):  
Maritza Torres ◽  
Hans de Cock ◽  
Adriana Marcela Celis Ramírez

Malassezia is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated with the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host–microbe interactions of Malassezia spp., and unraveling this implies the implementation of infection models. In this mini review, we present different models that have been implemented in fungal infections studies with greater attention to Malassezia spp. infections. These models range from in vitro (cell cultures and ex vivo tissue), to in vivo (murine models, rabbits, guinea pigs, insects, nematodes, and amoebas). We additionally highlight the alternative models that reduce the use of mammals as model organisms, which have been gaining importance in the study of fungal host–microbe interactions. This is due to the fact that these systems have been shown to have reliable results, which correlate with those obtained from mammalian models. Examples of alternative models are Caenorhabditis elegans, Drosophila melanogaster, Tenebrio molitor, and Galleria mellonella. These are invertebrates that have been implemented in the study of Malassezia spp. infections in order to identify differences in virulence between Malassezia species.


Author(s):  
Tiia Snäkä ◽  
Nicolas Fasel

Regulatory Nod-like receptors (NLRs) are a subgroup of the cytosolic NLR family of pathogen recognition receptors (PRRs). These receptors can tune the innate immune responses triggered by the activation of other PRRs by either augmenting or attenuating the activated pro-inflammatory signaling cascades. Nod-like receptor X1 (NLRX1) is the only known mitochondria-associated negative regulatory NLR. NLRX1 attenuates several inflammatory pathways and modulates cellular processes such as autophagy and mitochondrial function following infection or injury. Using both in vitro expression and in vivo experimental models, NLRX1 is extensively described in the context of anti-viral signaling and host-defense against invading pathogens. More recently, NLRX1 has also gained interest in the field of cancer and metabolism where NLRX1 functions to attenuate overzealous inflammation in various inflammatory and autoimmune diseases. However, the exact function of this novel receptor is still under debate and many, often contradictory, mechanisms of action together with cellular localizations have been proposed. Thus, a better understanding of the underlying mechanism is crucial for future research and development of novel therapeutical approaches. Here, we summarize the current findings on NLRX1 and discuss its role in both infectious and inflammatory context.


2020 ◽  
Vol 88 (3) ◽  
pp. 32
Author(s):  
Eduardo Costa ◽  
Tânia Ferreira-Gonçalves ◽  
Gonçalo Chasqueira ◽  
António S. Cabrita ◽  
Isabel V. Figueiredo ◽  
...  

Breast cancer is one of the most common cancers worldwide, which makes it a very impactful malignancy in the society. Breast cancers can be classified through different systems based on the main tumor features and gene, protein, and cell receptors expression, which will determine the most advisable therapeutic course and expected outcomes. Multiple therapeutic options have already been proposed and implemented for breast cancer treatment. Nonetheless, their use and efficacy still greatly depend on the tumor classification, and treatments are commonly associated with invasiveness, pain, discomfort, severe side effects, and poor specificity. This has demanded an investment in the research of the mechanisms behind the disease progression, evolution, and associated risk factors, and on novel diagnostic and therapeutic techniques. However, advances in the understanding and assessment of breast cancer are dependent on the ability to mimic the properties and microenvironment of tumors in vivo, which can be achieved through experimentation on animal models. This review covers an overview of the main animal models used in breast cancer research, namely in vitro models, in vivo models, in silico models, and other models. For each model, the main characteristics, advantages, and challenges associated to their use are highlighted.


Biomolecules ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 160
Author(s):  
Oliwia Koszła ◽  
Katarzyna M. Targowska-Duda ◽  
Ewa Kędzierska ◽  
Agnieszka A. Kaczor

Schizophrenia (SZ) is a complex psychiatric disorder characterized by positive, negative, and cognitive symptoms, and is not satisfactorily treated by current antipsychotics. Progress in understanding the basic pathomechanism of the disease has been hampered by the lack of appropriate models. In order to develop modern drugs against SZ, efficient methods to study them in in vitro and in vivo models of this disease are required. In this review a short presentation of current hypotheses and concepts of SZ is followed by a description of current progress in the field of SZ experimental models. A critical discussion of advantages and limitations of in vitro models and pharmacological, genetic, and neurodevelopmental in vivo models for positive, negative, and cognitive symptoms of the disease is provided. In particular, this review concerns the important issue of how cellular and animal systems can help to meet the challenges of modeling the disease, which fully manifests only in humans, as experimental studies of SZ in humans are limited. Next, it is emphasized that novel clinical candidates should be evaluated in animal models for treatment-resistant SZ. In conclusion, the plurality of available in vitro and in vivo models is a consequence of the complex nature of SZ, and there are extensive possibilities for their integration. Future development of more efficient antipsychotics reflecting the pleiotropy of symptoms in SZ requires the incorporation of various models into one uniting model of the multifactorial disorder and use of this model for the evaluation of new drugs.


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