Endometriosis related sex steroid hormones, hypothalamic pituitary gonadal axis hormones and related animal modeling: A comprehensive review of published articles and endometriosis induction methods from 2010 to 2021 with scoring based approach

Abstract Endometriosis is an enigmatic gynecological disease initiated by the ectopic growth of endometrial tissue and causes critical symptoms such as chronic pelvic pain, cyclic menstrual pain, subfertility or infertility. Considering extensive investigations for explaining the underlying pathophysiology of endometriosis, origin and distinctive processes which lead to endometritic state are not completely understood. In this comprehensive review, studies published from 2010 to 2021 are reviewed in order to provide a bright insight through the applications of translational animal models and endometriosis induction methods for evaluation of endometriosis pathogenesis and treatment. We provided method based inclusion criteria and reviewed all hormone-based studies with concentration on animal models. Additionally, studies with novel induction methods and approaches are categorized separately and analyzed by a novel scoring table for suitability of further investigations. Eventually, our scoring system suggested that the best-evaluated animal model for hormone related endometriosis studies is an “unopposed estrogenicity baboon model of endometriosis”.

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Animal Models of Mood Disorders

10.1093/med/9780190681425.003.0026 ◽

2017 ◽

Author(s):

Lyonna F. Alcantara ◽

Eric M. Parise ◽

Carlos A. Bolaños-Guzmán

Keyword(s):

Animal Models ◽

Mood Disorders ◽

Emotional Stress ◽

Social Defeat ◽

Neuropsychiatric Disorders ◽

Animal Modeling ◽

Complex Models ◽

Stress Influences ◽

Underlying Pathophysiology

Animal modeling has advanced our understanding of the underlying pathophysiology of human neuropsychiatric disorders and facilitated development of safer, more efficient medications. Similar to humans with depression, rodents exposed to various stress paradigms exhibit aberrant responses to rewarding stimuli, along with hormonal and immunological dysregulation. Development of more complex models, such as social defeat, has led to a firmer grasp of the mechanisms mediating resilience and susceptibility to stress; and adapted versions of social defeat have yielded insights into how emotional stress influences development of mood disorders. This chapter focuses on stress-induced models of mood disorders and outlines how a depression-like phenotype is induced and tested in rodents.

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Methods Used and Application of the Mouse Grimace Scale in Biomedical Research 10 Years On: A Scoping Review

Animals ◽

10.3390/ani11030673 ◽

2021 ◽

Vol 11 (3) ◽

pp. 673

Author(s):

Alexandra L. Whittaker ◽

Yifan Liu ◽

Timothy H. Barker

Keyword(s):

Animal Models ◽

Mouse Models ◽

Biomedical Research ◽

Scoping Review ◽

Facial Features ◽

Inclusion Criteria ◽

Academic Literature ◽

Research Fields ◽

Neuroscience Research ◽

Wide Range

The Mouse Grimace Scale (MGS) was developed 10 years ago as a method for assessing pain through the characterisation of changes in five facial features or action units. The strength of the technique is that it is proposed to be a measure of spontaneous or non-evoked pain. The time is opportune to map all of the research into the MGS, with a particular focus on the methods used and the technique’s utility across a range of mouse models. A comprehensive scoping review of the academic literature was performed. A total of 48 articles met our inclusion criteria and were included in this review. The MGS has been employed mainly in the evaluation of acute pain, particularly in the pain and neuroscience research fields. There has, however, been use of the technique in a wide range of fields, and based on limited study it does appear to have utility for pain assessment across a spectrum of animal models. Use of the method allows the detection of pain of a longer duration, up to a month post initial insult. There has been less use of the technique using real-time methods and this is an area in need of further research.

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P013 The JAK-3 and TYK-2 / STAT pathways are activated in moderate to severe ulcerative colitis

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjz203.142 ◽

2020 ◽

Vol 14 (Supplement_1) ◽

pp. S136-S137

Author(s):

M Loza ◽

J M Brea ◽

C Calviño-Suarez ◽

I Baston-Rey ◽

R Ferreiro-Iglesias ◽

...

Keyword(s):

Ulcerative Colitis ◽

Animal Models ◽

Inflammatory Response ◽

Western Blot ◽

Signalling Pathways ◽

Target Engagement ◽

Inclusion Criteria ◽

Phosphorylated Proteins ◽

Single Centre Study ◽

Stat Pathway

Abstract Background Ulcerative colitis (UC) is a chronic, progressive and disabling disease with a complex pathology of unknown aetiology influenced by genetic, environmental and microbiota factors that lead to an immunological and inflammatory response in the colon. Janus Activated Kinase (JAK) family plays a key role in modulating the adaptive and innate inflammatory response. The JAK/STAT pathway involvement in UC has been demonstrated in both animal models and human studies. Thus, overexpressed JAK-3 has been detected in the intestine of patients with UC, suggesting a key role in their pathophysiology and the inhibition of TYK-2 in animal models resulted in an improvement of the disease, which would explain its implication in the inflammatory process. We hypothesise here that there could be an activation of JAK-3 and TYK-2 signalling pathways in UC patients. Thus, we aimed to detect the activation of both signalling pathways by means of western-blot studies in UC patient samples Methods A prospective, observational single-centre study was designed. Inclusion criteria were adult patients with endoscopic active UC (more than Mayo-0) confirmed in a programmed colonoscopy. All patients signed informed consent. Samples were obtained from overstock of routine biopsies in the more severe segment affected of the large bowel. Tissues were homogenised and processed in order to obtain cell lysates by employing RIPA buffer and ultrasounds. The degree of activation of the JAK-3 and TYK-2 pathways was measured by detecting the phosphorylation of both targets as well as of STAT1, STAT3, STAT4, STAT5 and STAT6 through western blot by employing specific antibodies for total and phosphorylated proteins. Results 19 UC patients were consecutively included. Mean age was 46 years old. 53% were female, 47% were extensive colitis (E3) and 53% left-side colitis (E2). Regarding endoscopic activity, 26% had Mayo-1, 53% Mayo-2, and 21% Mayo-3. Immunoreactive bands for both phosphorylated JAK-3 and TYK-2 were detected in the biopsies from UC patients, evidencing that colonic inflammation leads to an activation of both targets. The study of STATs phosphorylation showed immunoreactive bands for phosphorylated forms of STAT1, STAT3, STAT4, STAT5 and STAT6 confirming the activation of both signalling-pathways in these patients (Figure 1). Conclusion The developed translational workflows involving basic/clinical research confirm the activation of both JAK-3 and TYK-2-dependent signalling pathways in UC patients, validating both kinases as targets for treating UC. The developed methodology allows studying the target engagement for future JAK-3/ TYK-2 inhibitors employed in clinical trials.

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Nonsteroidal Anti-Inflammatory Drugs and Their Neuroprotective Role After an Acute Spinal Cord Injury: A Systematic Review of Animal Models

Global Spine Journal ◽

10.1177/2192568220901689 ◽

2020 ◽

pp. 219256822090168

Author(s):

Mark J. Lambrechts ◽

James L. Cook

Keyword(s):

Systematic Review ◽

Spinal Cord ◽

Animal Models ◽

Motor Function ◽

Spinal Cord Injuries ◽

Inclusion Criteria ◽

Improve Motor Function ◽

Cord Injury ◽

Inflammatory Drugs ◽

Anti Inflammatory

Study Design: Systematic review. Objective: Spinal cord injuries (SCIs) resulting in motor deficits can be devastating injuries resulting in millions of health care dollars spent per incident. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a potential class of drugs that could improve motor function after an SCI. This systematic review utilizes PRISMA guidelines to evaluate the effectiveness of NSAIDs for SCI. Methods: PubMed/MEDLINE, CINAHL, PsycINFO, Embase, and Scopus were reviewed linking the keywords of “ibuprofen,” “meloxicam,” “naproxen,” “ketorolac,” “indomethacin,” “celecoxib,” “ATB-346,” “NSAID,” and “nonsteroidal anti-inflammatory drug” with “spinal.” Results were reviewed for relevance and included if they met inclusion criteria. The SYRCLE checklist was used to assess sources of bias. Results: A total of 2960 studies were identified in the PubMed/MEDLINE database using the above-mentioned search criteria. A total of 461 abstracts were reviewed in Scopus, 340 in CINAHL, 179 in PsycINFO, and 7632 in Embase. A total of 15 articles met the inclusion criteria. Conclusions: NSAIDs’ effectiveness after SCI is largely determined by its ability to inhibit Rho-A. NSAIDs are a promising therapeutic option in acute SCI patients because they appear to decrease cord edema and inflammation, increase axonal sprouting, and improve motor function with minimal side effects. Studies are limited by heterogeneity, small sample size, and the use of animal models, which might not replicate the therapeutic effects in humans. There are no published human studies evaluating the safety and efficacy of these drugs after a traumatic cord injury. There is a need for well-designed prospective studies evaluating ibuprofen or indomethacin after adult spinal cord injuries.

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Animal Models of Urologic Chronic Pelvic Pain Syndromes: Findings From the Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network

Urology ◽

10.1016/j.urology.2015.03.007 ◽

2015 ◽

Vol 85 (6) ◽

pp. 1454-1465 ◽

Cited By ~ 22

Author(s):

Henry Lai ◽

Robert W. Gereau ◽

Yi Luo ◽

Michael O'Donnell ◽

Charles N. Rudick ◽

...

Keyword(s):

Animal Models ◽

Pelvic Pain ◽

Chronic Pelvic Pain ◽

Multidisciplinary Approach ◽

Research Network ◽

Pain Research ◽

Pain Syndromes

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Animal models in the neurotoxicology of 2,4-D

Human & Experimental Toxicology ◽

10.1177/0960327119860172 ◽

2019 ◽

Vol 38 (10) ◽

pp. 1178-1182 ◽

Cited By ~ 2

Author(s):

LM Freitas ◽

LP de Assis Valadares ◽

MGM Camozzi ◽

PG de Oliveira ◽

MR Ferreira Machado ◽

...

Keyword(s):

Nervous System ◽

Animal Models ◽

Motor Activity ◽

Biochemical Analysis ◽

Brain Area ◽

Behavioral Effect ◽

Comprehensive Review ◽

Locomotor Patterns ◽

Chicken Eggs ◽

The Brain

2,4-D is a selective pre- and postemergence herbicide used for several crops. It is hazardous for the environment and risk for humans; therefore, several studies attempt to evaluate its effects and consequences of its use. The nervous system is supposedly a target for this herbicide, and this comprehensive review gathers the information about animal models that have been used for the study of the neurotoxicity of 2,4-D. The studies used several methods to evaluate the neurotoxicity of this herbicide, most of which used rodents, mainly rats, two used fish, and one used chicken eggs. The main behavioral effect observed concerned alterations in locomotor patterns and reduced motor activity. Biochemical analysis showed decreased levels of serotonin (5-HT) and increased levels of its metabolites and increased or decreased levels of DA and its metabolites depending on the brain area analyzed. Hypomyelination is also a possible effect of 2,4-D when the exposure occurs during the proliferation and development of the oligodendrocytes. The worst neuropathologic effects were observed in fish. Since most studies focused on the neurotoxicity of 2,4-D in rodents, the effect it may have on other species and groups of animals, especially with different physiology, is unclear and it should be researched.

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Evidence of a wide gap between COVID-19 in humans and animal models: a systematic review

Critical Care ◽

10.1186/s13054-020-03304-8 ◽

2020 ◽

Vol 24 (1) ◽

Author(s):

Salleh N. Ehaideb ◽

Mashan L. Abdullah ◽

Bisher Abuyassin ◽

Abderrezak Bouchama

Keyword(s):

Animal Models ◽

Nonhuman Primates ◽

Clinical Manifestations ◽

Full Recovery ◽

Severe Illness ◽

Original Research ◽

Lung Pathology ◽

Inclusion Criteria ◽

Hypoxemic Respiratory Failure ◽

Wide Gap

Abstract Background Animal models of COVID-19 have been rapidly reported after the start of the pandemic. We aimed to assess whether the newly created models reproduce the full spectrum of human COVID-19. Methods We searched the MEDLINE, as well as BioRxiv and MedRxiv preprint servers for original research published in English from January 1 to May 20, 2020. We used the search terms (COVID-19) OR (SARS-CoV-2) AND (animal models), (hamsters), (nonhuman primates), (macaques), (rodent), (mice), (rats), (ferrets), (rabbits), (cats), and (dogs). Inclusion criteria were the establishment of animal models of COVID-19 as an endpoint. Other inclusion criteria were assessment of prophylaxis, therapies, or vaccines, using animal models of COVID-19. Result Thirteen peer-reviewed studies and 14 preprints met the inclusion criteria. The animals used were nonhuman primates (n = 13), mice (n = 7), ferrets (n = 4), hamsters (n = 4), and cats (n = 1). All animals supported high viral replication in the upper and lower respiratory tract associated with mild clinical manifestations, lung pathology, and full recovery. Older animals displayed relatively more severe illness than the younger ones. No animal models developed hypoxemic respiratory failure, multiple organ dysfunction, culminating in death. All species elicited a specific IgG antibodies response to the spike proteins, which were protective against a second exposure. Transient systemic inflammation was observed occasionally in nonhuman primates, hamsters, and mice. Notably, none of the animals unveiled a cytokine storm or coagulopathy. Conclusions Most of the animal models of COVID-19 recapitulated mild pattern of human COVID-19 with full recovery phenotype. No severe illness associated with mortality was observed, suggesting a wide gap between COVID-19 in humans and animal models.

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Special Issue: Animal Modeling in Cancer

Genes ◽

10.3390/genes11091009 ◽

2020 ◽

Vol 11 (9) ◽

pp. 1009

Author(s):

Vladimir Korinek

Keyword(s):

Animal Models ◽

High Throughput Sequencing ◽

Tumor Biology ◽

Tumor Formation ◽

Diagnostic Tools ◽

Special Issue ◽

Cancer Treatments ◽

Behavioral Traits ◽

Animal Modeling

Recent advances in high-throughput sequencing techniques have significantly accelerated the development of personalized diagnostic tools and cancer treatments. However, a comparative analysis of experimental animals that share similar genetic, physiological, and behavioral traits with humans remains the basis for understanding the pathological mechanisms associated with human diseases, including cancer. The generation and characterization of suitable animal models mimicking tumor growth and progression thus represents an important “component” of tumor biology research. The presented Special Issue contains ten review articles, which, based on data obtained from various animal models, summarize a number of aspects of the tumor formation process that include gastrointestinal neoplasia, breast cancer, hematological malignancies, melanoma, and brain tumors. This Special Issue nicely illustrates how the study of suitable living models uncovers not only the fundamental molecular and cellular bases of neoplastic growth, but might also indicate approaches to efficient cancer treatments.

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