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The Journal of Antibiotics Sep 2020Ivermectin proposes many potentials effects to treat a range of diseases, with its antimicrobial, antiviral, and anti-cancer properties as a wonder drug. It is highly...
Ivermectin proposes many potentials effects to treat a range of diseases, with its antimicrobial, antiviral, and anti-cancer properties as a wonder drug. It is highly effective against many microorganisms including some viruses. In this comprehensive systematic review, antiviral effects of ivermectin are summarized including in vitro and in vivo studies over the past 50 years. Several studies reported antiviral effects of ivermectin on RNA viruses such as Zika, dengue, yellow fever, West Nile, Hendra, Newcastle, Venezuelan equine encephalitis, chikungunya, Semliki Forest, Sindbis, Avian influenza A, Porcine Reproductive and Respiratory Syndrome, Human immunodeficiency virus type 1, and severe acute respiratory syndrome coronavirus 2. Furthermore, there are some studies showing antiviral effects of ivermectin against DNA viruses such as Equine herpes type 1, BK polyomavirus, pseudorabies, porcine circovirus 2, and bovine herpesvirus 1. Ivermectin plays a role in several biological mechanisms, therefore it could serve as a potential candidate in the treatment of a wide range of viruses including COVID-19 as well as other types of positive-sense single-stranded RNA viruses. In vivo studies of animal models revealed a broad range of antiviral effects of ivermectin, however, clinical trials are necessary to appraise the potential efficacy of ivermectin in clinical setting.
Topics: Animals; Antiviral Agents; Betacoronavirus; Cell Line; DNA Viruses; Disease Models, Animal; Global Health; Humans; Ivermectin; Molecular Structure; RNA Viruses; SARS-CoV-2
PubMed: 32533071
DOI: 10.1038/s41429-020-0336-z -
Nutrients Oct 2020Citicoline is a chemical compound involved in the synthesis of cell membranes. It also has other, not yet explained functions. Research on the use of citicoline is...
Citicoline is a chemical compound involved in the synthesis of cell membranes. It also has other, not yet explained functions. Research on the use of citicoline is conducted in neurology, ophthalmology, and psychiatry. Citicoline is widely available as a dietary supplement. It is often used to enhance cognitive functions. In our article, accessible databases were searched for articles regarding citicoline use in neurological diseases. This article has a systemic review form. After rejecting non-eligible reports, 47 remaining articles were reviewed. The review found that citicoline has been proven to be a useful compound in preventing dementia progression. It also enhances cognitive functions among healthy individuals and improves prognosis after stroke. In an animal model of nerve damage and neuropathy, citicoline stimulated regeneration and lessened pain. Among patients who underwent brain trauma, citicoline has an unclear clinical effect. Citicoline has a wide range of effects and could be an essential substance in the treatment of many neurological diseases. Its positive impact on learning and cognitive functions among the healthy population is also worth noting.
Topics: Animals; Brain Injuries, Traumatic; Cognition; Cytidine Diphosphate Choline; Dementia; Disease Models, Animal; Humans; Meta-Analysis as Topic; Nervous System Diseases; Neuralgia; Neurotransmitter Agents; Peripheral Nervous System; Stroke
PubMed: 33053828
DOI: 10.3390/nu12103113 -
Journal of Pharmacy & Bioallied Sciences Jun 2021Extensive work is being done to form targeted drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, it is imperative to have a... (Review)
Review
Extensive work is being done to form targeted drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, it is imperative to have a safe and effective vaccine against the same to win the war against this pandemic. For creating an efficacious vaccine, a proper animal model needs to be selected which can have an acceptable similarity of response as well as effects when administered to humans. For the present research, extensive search was conducted in MEDLINE and bioRxiv and medRxiv servers which were published in the English language from January 1, 2020, to August 20, 2020. Search terms included animal models, SARS-CoV-2, COVID-19, immune response against coronavirus, nonhuman primates, mice, ferrets, and macaques. In our study, creating an adequate immune response mimicking the response as in humans, as the endpoint, was considered as inclusion criterion while assessment of any additional therapies like safety as well as minimal tolerable dose using animal models as well as formation of adequate sample size of these models against COVID-19 was not considered. In our search, 163 articles were shortlisted, of them only 20 articles were finally included in our study which addressed to our inclusion and exclusion criterion. Our research articles focused on nonhuman primates, mice, hamsters, ferrets, cats, and dogs, with the main goal to investigate the role of animal models in the pathogenesis of COVID-19. It was evident in our research that animal models only mimic limited signs and symptoms experienced in COVID infection as compared to infections in humans. However, they are still essential to understand the pathogenesis, transmissibility of viral particles, and vaccine testing.
PubMed: 34447038
DOI: 10.4103/jpbs.JPBS_749_20 -
Frontiers in Bioengineering and... 2021Pathologies related to the cardiovascular system are the leading causes of death worldwide. One of the main treatments is conventional surgery with autologous... (Review)
Review
Pathologies related to the cardiovascular system are the leading causes of death worldwide. One of the main treatments is conventional surgery with autologous transplants. Although donor grafts are often unavailable, tissue-engineered vascular grafts (TEVGs) show promise for clinical treatments. A systematic review of the recent scientific literature was performed using PubMed (Medline) and Web of Science databases to provide an overview of the state-of-the-art in TEVG development. The use of TEVG in human patients remains quite restricted owing to the presence of vascular stenosis, existence of thrombi, and poor graft patency. A total of 92 original articles involving human patients and animal models were analyzed. A meta-analysis of the influence of the vascular graft diameter on the occurrence of thrombosis and graft patency was performed for the different models analyzed. Although there is no ideal animal model for TEVG research, the murine model is the most extensively used. Hybrid grafting, electrospinning, and cell seeding are currently the most promising technologies. The results showed that there is a tendency for thrombosis and non-patency in small-diameter grafts. TEVGs are under constant development, and research is oriented towards the search for safe devices.
PubMed: 34805124
DOI: 10.3389/fbioe.2021.771400 -
International Journal of Molecular... Jun 2023Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterised by cognitive impairment, and amyloid-β plaques and neurofibrillary tau tangles at... (Review)
Review
Alzheimer's Disease (AD) is a progressive neurodegenerative disorder characterised by cognitive impairment, and amyloid-β plaques and neurofibrillary tau tangles at neuropathology. Capsaicin is a spicy-tasting compound found in chili peppers, with anti-inflammatory, antioxidant, and possible neuroprotective properties. Capsaicin intake has been associated with greater cognitive function in humans, and attenuating aberrant tau hyperphosphorylation in a rat model of AD. This systematic review discusses the potential of capsaicin in improving AD pathology and symptoms. A systematic analysis was conducted on the effect of capsaicin on AD-associated molecular changes, cognitive and behaviour resulting in 11 studies employing rodents and/or cell cultures, which were appraised with the Cochrane Risk of Bias tool. Ten studies showed capsaicin attenuated tau deposition, apoptosis, and synaptic dysfunction; was only weakly effective on oxidative stress; and had conflicting effects on amyloid processing. Eight studies demonstrated improved spatial and working memory, learning, and emotional behaviours in rodents following capsaicin treatment. Overall, capsaicin showed promise in improving AD-associated molecular, cognitive, and behavioural changes in cellular and animal models, and further investigations are recommended to test the readily available bioactive, capsaicin, to treat AD.
Topics: Humans; Rats; Animals; Alzheimer Disease; Capsaicin; Amyloid beta-Peptides; Neurofibrillary Tangles; Cognition; tau Proteins; Disease Models, Animal
PubMed: 37373321
DOI: 10.3390/ijms241210176 -
Kidney International Feb 2022Chronic kidney disease (CKD) triggers the risk of developing uremic cardiomyopathy as characterized by cardiac hypertrophy, fibrosis and functional impairment.... (Meta-Analysis)
Meta-Analysis
Chronic kidney disease (CKD) triggers the risk of developing uremic cardiomyopathy as characterized by cardiac hypertrophy, fibrosis and functional impairment. Traditionally, animal studies are used to reveal the underlying pathological mechanism, although variable CKD models, mouse strains and readouts may reveal diverse results. Here, we systematically reviewed 88 studies and performed meta-analyses of 52 to support finding suitable animal models for future experimental studies on pathological kidney-heart crosstalk during uremic cardiomyopathy. We compared different mouse strains and the direct effect of CKD on cardiac hypertrophy, fibrosis and cardiac function in "single hit" strategies as well as cardiac effects of kidney injury combined with additional cardiovascular risk factors in "multifactorial hit" strategies. In C57BL/6 mice, CKD was associated with a mild increase in cardiac hypertrophy and fibrosis and marginal systolic dysfunction. Studies revealed high variability in results, especially regarding hypertrophy and systolic function. Cardiac hypertrophy in CKD was more consistently observed in 129/Sv mice, which express two instead of one renin gene and more consistently develop increased blood pressure upon CKD induction. Overall, "multifactorial hit" models more consistently induced cardiac hypertrophy and fibrosis compared to "single hit" kidney injury models. Thus, genetic factors and additional cardiovascular risk factors can "prime" for susceptibility to organ damage, with increased blood pressure, cardiac hypertrophy and early cardiac fibrosis more consistently observed in 129/Sv compared to C57BL/6 strains.
Topics: Animals; Cardiomyopathies; Disease Models, Animal; Fibrosis; Mice; Mice, Inbred C57BL; Renal Insufficiency, Chronic
PubMed: 34774555
DOI: 10.1016/j.kint.2021.10.025 -
Brain Sciences Feb 2020Intracranial aneurysms (IA) are characterized by weakened cerebral vessel walls that may lead to rupture and subarachnoid hemorrhage. The mechanisms behind their... (Review)
Review
Intracranial aneurysms (IA) are characterized by weakened cerebral vessel walls that may lead to rupture and subarachnoid hemorrhage. The mechanisms behind their formation and progression are yet unclear and warrant preclinical studies. This systematic review aims to provide a comprehensive, systematic overview of available animal models for the study of IA pathobiology. We conducted a systematic literature search using the PubMed database to identify preclinical studies employing IA animal models. Suitable articles were selected based on predefined eligibility criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Included studies were reviewed and categorized according to the experimental animal and aneurysm model. Of 4266 returned results, 3930 articles were excluded based on the title and/or abstract and further articles after screening the full text, leaving 123 studies for detailed analysis. A total of 20 different models were found in rats (nine), mice (five), rabbits (four), and dogs (two). Rat models constituted the most frequently employed intracranial experimental aneurysm model (79 studies), followed by mice (31 studies), rabbits (12 studies), and two studies in dogs. The most common techniques to induce cerebral aneurysms were surgical ligation of the common carotid artery with subsequent induction of hypertension by ligation of the renal arteries, followed by elastase-induced creation of IAs in combination with corticosterone- or angiotensin-induced hypertension. This review provides a comprehensive summary of the multitude of available IA models to study various aspects of aneurysm formation, growth, and rupture. It will serve as a useful reference for researchers by facilitating the selection of the most appropriate model and technique to answer their scientific question.
PubMed: 32120907
DOI: 10.3390/brainsci10030134 -
Disease Models & Mechanisms Jun 2023As kidney diseases affect ∼10% of the world population, understanding the underlying mechanisms and developing therapeutic interventions are of high importance....
As kidney diseases affect ∼10% of the world population, understanding the underlying mechanisms and developing therapeutic interventions are of high importance. Although animal models have enhanced knowledge of disease mechanisms, human (patho-)physiology may not be adequately represented in animals. Developments in microfluidics and renal cell biology have enabled the development of dynamic models to study renal (patho-)physiology in vitro. Allowing inclusion of human cells and combining different organ models, such as kidney-on-a-chip (KoC) models, enable the refinement and reduction of animal experiments. We systematically reviewed the methodological quality, applicability and effectiveness of kidney-based (multi-)organ-on-a-chip models, and describe the state-of-the-art, strengths and limitations, and opportunities regarding basic research and implementation of these models. We conclude that KoC models have evolved to complex models capable of mimicking systemic (patho-)physiological processes. Commercial chips and human induced pluripotent stem cells and organoids are important for KoC models to study disease mechanisms and assess drug effects, even in a personalized manner. This contributes to the Reduction, Refinement and Replacement of animal models for kidney research. A lack of reporting of intra- and inter-laboratory reproducibility and translational capacity currently hampers implementation of these models.
Topics: Animals; Humans; Reproducibility of Results; Induced Pluripotent Stem Cells; Kidney; Kidney Diseases; Lab-On-A-Chip Devices
PubMed: 37334839
DOI: 10.1242/dmm.050113 -
Journal of Translational Medicine Oct 2023Animal models are widely used to study pathological processes and drug (side) effects in a controlled environment. There is a wide variety of methods available for... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Animal models are widely used to study pathological processes and drug (side) effects in a controlled environment. There is a wide variety of methods available for establishing animal models depending on the research question. Commonly used methods in tumor research include xenografting cells (established/commercially available or primary patient-derived) or whole tumor pieces either orthotopically or heterotopically and the more recent genetically engineered models-each type with their own advantages and disadvantages. The current systematic review aimed to investigate the meningioma model types used, perform a meta-analysis on tumor take rate (TTR), and perform critical appraisal of the included studies. The study also aimed to assess reproducibility, reliability, means of validation and verification of models, alongside pros and cons and uses of the model types.
METHODS
We searched Medline, Embase, and Web of Science for all in vivo meningioma models. The primary outcome was tumor take rate. Meta-analysis was performed on tumor take rate followed by subgroup analyses on the number of cells and duration of incubation. The validity of the tumor models was assessed qualitatively. We performed critical appraisal of the methodological quality and quality of reporting for all included studies.
RESULTS
We included 114 unique records (78 using established cell line models (ECLM), 21 using primary patient-derived tumor models (PTM), 10 using genetically engineered models (GEM), and 11 using uncategorized models). TTRs for ECLM were 94% (95% CI 92-96) for orthotopic and 95% (93-96) for heterotopic. PTM showed lower TTRs [orthotopic 53% (33-72) and heterotopic 82% (73-89)] and finally GEM revealed a TTR of 34% (26-43).
CONCLUSION
This systematic review shows high consistent TTRs in established cell line models and varying TTRs in primary patient-derived models and genetically engineered models. However, we identified several issues regarding the quality of reporting and the methodological approach that reduce the validity, transparency, and reproducibility of studies and suggest a high risk of publication bias. Finally, each tumor model type has specific roles in research based on their advantages (and disadvantages).
SYSTEMATIC REVIEW REGISTRATION
PROSPERO-ID CRD42022308833.
Topics: Animals; Humans; Meningeal Neoplasms; Meningioma; Reproducibility of Results; Disease Models, Animal
PubMed: 37898750
DOI: 10.1186/s12967-023-04620-7 -
International Journal of Molecular... Aug 2023Protein-bound uremic toxins (PBUTs) are associated with the progression of chronic kidney disease (CKD) and its associated morbidity and mortality. The conventional... (Review)
Review
Protein-bound uremic toxins (PBUTs) are associated with the progression of chronic kidney disease (CKD) and its associated morbidity and mortality. The conventional dialysis techniques are unable to efficiently remove PBUTs due to their plasma protein binding. Therefore, novel approaches are being developed, but these require validation in animals before clinical trials can begin. We conducted a systematic review to document PBUT concentrations in various models and species. The search strategy returned 1163 results for which abstracts were screened, resulting in 65 full-text papers for data extraction (rats ( = 41), mice ( = 17), dogs ( = 3), cats ( = 4), goats ( = 1), and pigs ( = 1)). We performed descriptive and comparative analyses on indoxyl sulfate (IS) concentrations in rats and mice. The data on large animals and on other PBUTs were too heterogeneous for pooled analysis. Most rodent studies reported mean uremic concentrations of plasma IS close to or within the range of those during kidney failure in humans, with the highest in tubular injury models in rats. Compared to nephron loss models in rats, a greater rise in plasma IS compared to creatinine was found in tubular injury models, suggesting tubular secretion was more affected than glomerular filtration. In summary, tubular injury rat models may be most relevant for the in vivo validation of novel PBUT-lowering strategies for kidney failure in humans.
Topics: Humans; Rats; Mice; Animals; Dogs; Swine; Uremic Toxins; Toxins, Biological; Models, Animal; Creatinine; Goats; Indican; Renal Insufficiency
PubMed: 37686004
DOI: 10.3390/ijms241713197