Animal Studies Research Articles

Adult Neoneurogenesis and Oligodendrogenesis in Multiple Sclerosis: A Systematic Review of Human and Animal Studies.

Introduction: The subventricular zone promotes remyelination through activation differentiation of oligodendroglial precursor cells (OPCs) and neural stem cells (NSCs) into mature oligodendrocytes and thus in the adult brain. In multiple sclerosis (MS) this regenerative capability is halted resulting in neurodegeneration. We aimed to systematically search and synthesize evidence on mechanisms and phenomena associated with subventricular zone (SVZ) dysfunction in MS. Materials and Methods: Our systematic review was reported according to the PRISMA-ScR statement. MEDLINE, SCOPUS, ProQuest, and Google Scholar were searched using the terms "subventricular zone" and "multiple sclerosis," including English-written invivo and postmortem studies. Results: Twenty studies were included. Thirteen studies on models of experimental autoimmune encephalomyelitis (EAE) reported among others strong stathmin immunoreactivity in the SVZ of EAE models, the role of MOG immunization in neurogenesis impairment, the effect of parenchymal OPCs and NSCs in myelin repair, and the importance of ependymal cells (E1/E2) and ciliated B1 cells in SVZ stem cell signaling. CXCR4 signaling and transcriptional profiles of SVZ microglia, Gli1 pathway, and galactin-3 were also explored. Studies in humans demonstrated microstructural SVZ damage in progressive MS and the persistence of black holes near the SVZ, whereas postmortem confirmed the generation of polysialic acid-neural cell adhesion molecule and NG2-positive progenitors through SVZ activation, SVZ stathmin immunoreactivity, Shh pathway, and Gal-3 upregulation. Discussion: Oligodendrogenesis defects translate to reduced remyelination, a hallmark of MS that determines its end-phenotype and disease course. Conclusion: The role of inflammation and subsequent SVZ microenvironment disruption is evident in MS pathology.

Study on the hemodynamic effects of different pulsatile working modes of a rotary blood pump using a microfluidic platform that realizes in vitro cell culture effectively.

Rotary blood pumps (RBPs) operating at a constant speed generate non-physiologic blood pressure and flow rate, which can cause endothelial dysfunction, leading to adverse clinical events in peripheral blood vessels and other organs. Notably, pulsatile working modes of the RBP can increase vascular pulsatility to improve arterial endothelial function. However, the laws and related mechanisms of differentially regulating arterial endothelial function under different pulsatile working modes are still unclear. This knowledge gap hinders the optimal selection of the RBP working modes. To address these issues, this study developed a multi-element in vitro endothelial cell culture system (ECCS), which could realize in vitro cell culture effectively and accurately reproduce blood pressure, shear stress, and circumferential strain in the arterial endothelial microenvironment. Performance of this proposed ECCS was validated with numerical simulation and flow experiments. Subsequently, this study investigated the effects of four different pulsation frequency modes that change once every 1-4-fold cardiac cycles (80, 40, 80/3, and 20 cycles per min, respectively) of the RBP on the expression of nitric oxide (NO) and reactive oxygen species (ROS) in endothelial cells. Results indicated that the 2-fold and 3-fold cardiac cycles significantly increased the production of NO and prevented the excessive generation of ROS, potentially minimizing the occurrence of endothelial dysfunction and related adverse events during the RBP support, and were consistent with animal study findings. In general, this study may provide a scientific basis for the optimal selection of the RBP working modes and potential treatment options for heart failure.

Impacts of pancreatic exocrine insufficiency on gut microbiota.

Pancreatic exocrine insufficiency (PEI) can be induced by various kinds of diseases, including chronic pancreatitis, acute pancreatitis, and post-pancreatectomy. The main pathogenetic mechanism of PEI involves the decline of trypsin synthesis, disorder of pancreatic fluid flow, and imbalance of secretion feedback. Animal studies have shown that PEI could induce gut bacterial overgrowth and dysbiosis, with the abundance of Lactobacillus and Bifidobacterium increasing the most, which could be partially reversed by pancreatic enzyme replacement therapy. Clinical studies have also confirmed the association between PEI and the dysbiosis of gut microbiota. Pancreatic exocrine secretions and changes in duodenal pH as well as bile salt malabsorption brought about by PEI may affect and shape the abundance and composition of gut microbiota. In turn, the gut microbiota may impact the pancreatic exocrine acinus through potential bidirectional crosstalk. Going forward, more and higher-quality studies are needed that focus on the mechanism underlying the impact of PEI on the gut microbiota.

Centring animal experience through comics-based research: The case of Pavlov’s dogs 

The focus of this article is the collaborative creation of Pavlov and the Kingdom of Dogs, a graphic nonfiction novel aimed at highlighting the lives of dogs experimented upon by Ivan Pavlov in late 19th and early 20th-century Russia. The novel delves into the intricate human-canine relationships within the context of St. Petersburg’s scientific, cultural, and political landscape. The collaboration between a researcher, a professional illustrator, and a script editor aimed to challenge anthropocentric narratives prevalent in historical representations of Pavlov and experimental science. Rooted in animal studies and psychology, this project explores the potential of arts-based methods to centre animals and their relationships within historical contexts. It aims to deepen depictions of animal experiences and agency while bridging the gap between human-animal studies and psychology, where attention to animal lives in research settings remains limited. By focusing on Pavlov’s experiments, the project seeks to redefine experimental animals as active historical subjects, contributing to broader discussions on human-animal relationships and ethical responsibilities. The article delineates the theoretical and methodological underpinnings of the graphic novel, provides insights into the comics-based research process, and discusses the affordances and challenges of this approach. It concludes by reflecting on the potential of comics-based research to engage both academic and public audiences, ultimately advocating for a deeper understanding of human-animal entanglements and their implications in contemporary society.

The developmental cognitive mechanism of learning algebraic rules from the dual-process theory perspective.

Rule learning is an important ability that enables human beings to adapt to nature and develop civilizations. There have been many discussions on the mechanism and characteristics of algebraic rule learning, but there are still controversies due to the lack of theoretical guidance. Based on the dual-process theory, this study discussed the following arguments for algebraic rule learning across human and animal studies: whether algebraic rule learning is simply Type 1 processing, whether algebraic rule learning is a domain-general ability, whether algebraic rule learning is shared by humans and animals, and whether an algebraic rule is learned consciously. Moreover, we propose that algebraic rule learning is possibly a cognitive process that combines both Type 1 and Type 2 processing. Further exploration is required to establish the essence and neural basis of algebraic rule learning.

Simultaneous reconstruction of 3D fluorescence distribution and object surface using structured light illumination and dual-camera detection

Fluorescence molecular tomography (FMT) serves as a noninvasive modality for visualizing volumetric fluorescence distribution within biological tissues, thereby proving to be an invaluable imaging tool for preclinical animal studies. The conventional FMT relies upon a point-by-point raster scan strategy, enhancing the dataset for subsequent reconstruction but concurrently elongating the data acquisition process. The resultant diminished temporal resolution has persistently posed a bottleneck, constraining its utility in dynamic imaging studies. We introduce a novel system capable of simultaneous FMT and surface extraction, which is attributed to the implementation of a rapid line scanning approach and dual-camera detection. The system performance was characterized through phantom experiments, while the influence of scanning line density on reconstruction outcomes has been systematically investigated via both simulation and experiments. In a proof-of-concept study, our approach successfully captures a moving fluorescence bolus in three dimensions with an elevated frame rate of approximately 2.5 seconds per frame, employing an optimized scan interval of 5 mm. The notable enhancement in the spatio-temporal resolution of FMT holds the potential to broaden its applications in dynamic imaging tasks, such as surgical navigation.

The effect of bone marrow derived cell therapies on hind limb perfusion, A systematic review and meta-analysis.

Administration of bone marrow (BM) derived cells to restore perfusion showed promising results in preclinical studies. However, clinical studies in chronic limb threatening ischemia (CLTI) demonstrated conflicting results. We conducted a systematic review and meta-analysis on preclinical studies to assess the efficacy of BM-derived cell administration in restoring relative perfusion in the hind limb ischemia model (HLI) and identify possible determinants of therapeutic efficacy. In vivo animal studies that assessed BM MNCs or BM MSCs in the HLI model and included relative perfusion as an outcome measure were identified using a systematic search in PubMed and EMBASE on January 10th, 2022. Risk of bias was assessed using SYRCLE's risk of bias tool. Study characteristics and outcome data on relative perfusion were extracted. A random effects meta-analysis was performed using the mean difference calculated from the maximum relative perfusion for each study arm in each study. 85 studies that comprised 1053 animals were included. Our meta-analysis shows a significant increase in perfusion in the affected limb after BM cell administration compared to the control (effect size 18.3 (95% CI 15.9 - 20.7, p<0.001). However, we observed a high heterogeneity between studies (I2 91%), which could not be explained by dose, species, cell type or administration route. The risk of several types of bias was unclear due to incomplete reporting. We also detected a substantial risk of publication bias in this evidence base. There is a beneficial effect of BM-derived cell therapy in animal models for CLTI. However, the certainty of the evidence is low according to GRADE assessment. Translational implementation of this method should take this into account.

Vascularized tumor models for the evaluation of drug delivery systems: a paradigm shift.

As the conversion rate of preclinical studies for cancer treatment is low, user-friendly models that mimic the pathological microenvironment and drug intake with high throughput are scarce. Animal models are key, but an alternative to reduce their use would be valuable. Vascularized tumor-on-chip models combine great versatility with scalable throughput and are easy to use. Several strategies to integrate both tumor and vascular compartments have been developed, but few have been used to assess drug delivery. Permeability, intra/extravasation, and free drug circulation are often evaluated, but imperfectly recapitulate the processes at stake. Indeed, tumor targeting and chemoresistance bypass must be investigated to design promising cancer therapeutics. In vitro models that would help the development of drug delivery systems (DDS) are thus needed. They would allow selecting good candidates before animal studies based on rational criteria such as drug accumulation, diffusion in the tumor, and potency, as well as absence of side damage. In this review, we focus on vascularized tumor models. First, we detail their fabrication, and especially the materials, cell types, and coculture used. Then, the different strategies of vascularization are described along with their classical applications in intra/extravasation or free drug assessment. Finally, current trends in DDS for cancer are discussed with an overview of the current efforts in the domain.

Unveiling the strategic discourse of european dairy industry pressure groups: A Critical Animal Studies perspective

This article examines the discourse of pressure groups within the European Dairy Industry (EDI) using a Critical Animal Studies perspective. The study first identifies the EDI as a powerful economic actor by analysing its key companies, pressure groups, and their relationships. Then, it analyses the discourse constructed and the rhetorical devices these interest groups use regarding 1) the animals exploited by the industry and 2) the nutritional recommendations influencing dietary guidelines. The dairy industry forms a significant economic and corporate conglomerate that actively influences food recommendations and maintains extensive coalitions and lobbying efforts. The EDI interest groups tailor their narrative to align with current environmental, health, and animal welfare concerns while paradoxically contradicting them. Notably, the interest groups entirely disregard the interests of animals in their discourse, representing them as inanimate objects devoid of sentience, autonomy, and individuality through a series of rhetorical devices.

Reward positivity affects temporal interval production in a continuous timing task.

The neural circuits of reward processing and interval timing (including the perception and production of temporal intervals) are functionally intertwined, suggesting that it might be possible for momentary reward processing to influence subsequent timing behavior. Previous animal and human studies have mainly focused on the effect of reward on interval perception, whereas its impact on interval production is less clear. In this study, we examined whether feedback, as an example of performance-contingent reward, biases interval production. We recorded EEG from 20 participants while they engaged in a continuous drumming task with different realistic tempos (1728 trials per participant). Participants received color-coded feedback after each beat about whether they were correct (on time) or incorrect (early or late). Regression-based EEG analysis was used to unmix the rapid occurrence of a feedback response called the reward positivity (RewP), which is traditionally observed in more slow-paced tasks. Using linear mixed modeling, we found that RewP amplitude predicted timing behavior for the upcoming beat. This performance-biasing effect of the RewP was interpreted as reflecting the impact of fluctuations in reward-related anterior cingulate cortex activity on timing, and the necessity of continuous paradigms to make such observations was highlighted.

The Induction of Combined Hyperthermal Ablation Effect of Irreversible Electroporation with Polydopamine Nanoparticle-Coated Electrodes

Irreversible electroporation (IRE) is a prominent non-thermal ablation method widely employed in clinical settings for the focal ablation therapy of solid tumors. Utilizing high-voltage, short-duration electric pulses, IRE induces perforation defects in the cell membrane, leading to apoptotic cell death. Despite the promise of irreversible electroporation (IRE) in clinical applications, it faces challenges concerning the coverage of target tissues for ablation, particularly when compared to other thermal ablation therapies such as radiofrequency ablation, microwave ablation, and cryoablation. This study aims to investigate the induced hyperthermal effect of IRE by applying a polydopamine nanoparticle (Dopa NP) coating on the electrode. We hypothesize that the induced hyperthermal effect enhances the therapeutic efficacy of IRE for cancer ablation. First, we observed the hyperthermal effect of IRE using Dopa NP-coated electrodes in hydrogel phantom models and then moved to in vivo models. In particular, in in vivo animal studies, the IRE treatment of rabbit hepatic lobes with Dopa NP-coated electrodes exhibited a two-fold higher increase in temperature (ΔT) compared to non-coated electrodes. Through a comprehensive analysis, we found that IRE treatment with Dopa NP-coated electrodes displayed the typical histological signatures of hyperthermal ablation, including the disruption of the hepatic cord and lobular structure, as well as the infiltration of erythrocytes. These findings unequivocally highlight the combined efficacy of IRE with Dopa NPs for electroporation and the hyperthermal ablation of target cancer tissues.

Correlations between heart sound components and hemodynamic variables

Although the esophageal stethoscope is used for continuous auscultation during general anesthesia, few studies have investigated phonocardiographic data as a continuous hemodynamic index. In this study, we aimed to induce hemodynamic variations and clarify the relationship between the heart sounds and hemodynamic variables through an experimental animal study. Changes in the cardiac contractility and vascular resistance were induced in anesthetized pigs by administering dobutamine, esmolol, phenylephrine, and nicardipine. In addition, a decrease in cardiac output was induced by restricting the venous return by clamping the inferior vena cava (IVC). The relationship between the hemodynamic changes and changes in the heart sound indices was analyzed. Experimental data from eight pigs were analyzed. The mean values of the correlation coefficients of changes in S1 amplitude (ΔS1amp) with systolic blood pressure (ΔSBP), pulse pressure (ΔPP), and ΔdP/dt during dobutamine administration were 0.94, 0.96, and 0.96, respectively. The mean values of the correlation coefficients of ΔS1amp with ΔSBP, ΔPP, and ΔdP/dt during esmolol administration were 0.80, 0.82, and 0.86, respectively. The hemodynamic changes caused by the administration of phenylephrine and nicardipine did not correlate significantly with changes in the heart rate. The S1 amplitude of the heart sound was significantly correlated with the hemodynamic changes caused by the changes in cardiac contractility but not with the variations in the vascular resistance. Heart sounds can potentially provide a non-invasive monitoring method to differentiate the cause of hemodynamic variations.

Health-Related Outcomes and Molecular Methods for the Characterization of A1 and A2 Cow’s Milk: Review and Update

A new trend in cow’s milk has emerged in the market called type A1 and A2 milk. These products have piqued the interest of both consumers and researchers. Recent studies suggest that A2 milk may have potential health benefits beyond that of A1 milk, which is why researchers are investigating this product further. It is interesting to note that the A1 and A2 milk types have area-specific characteristics compared to breed-specific characteristics. Extensive research has focused on milk derivatives obtained from cow’s milk, primarily through in vitro and animal studies. However, few clinical studies have been conducted in humans, and the results have been unsatisfactory. New molecular techniques for identifying A1 and A2 milk may help researchers develop new studies that can clarify certain controversies surrounding A1 milk. It is essential to exercise extreme caution when interpreting the updated literature. It has the potential to spread panic worldwide and have negative economic implications. Therefore, this study aims to investigate the differences between A1 and A2 milk in various research areas and clarify some aspects regarding these two types of milk.

The role of diabetes on the development of abdominal aortic aneurysms (AAA)

An abdominal aortic aneurysm (AAA) is a pathological local dilatation of the abdominal aorta that may develop from a variety of causes. With a 80% mortality rate, it is mainly linked to male gender, age above 65 years, smoking, and a family history of AAA. Ultrasonography is an effective method for screening males who are 65 or older for AAA. Endovascular aneurysm repair (EVAR) procedure reduces 30-day operative mortality and hospital stay, becoming a global standard. Both open and endovascular surgery aim to cut off the aneurysm's circulation, preventing it from rupturing. Diabetes mellitus (DM) may provide protection against regrowth and the need for additional intervention after endovascular AAA repair, thereby limiting the enlargement and rupture of AAAs. Hyperglycemia thickens the aortic walls and reduces wall stress in diabetic patients' abdominal aortas. It stabilizes collagen structure and promotes the synthesis of collagen type IV. Anti-diabetic drugs like metformin, thiazolidinedione, and dipeptidyl peptidase 4 inhibitors (DPP-4i) have been shown in both animal and human studies to protect against aortic aneurysms. In a dose-response pattern, these antidiabetic drugs may lower the prevalence, incidence, and enlargement rate of AAA.

From psychophysiology to brain imaging: forty-five years MMN history of investigating acoustic change sensitivity.

Forty-five years have passed since the first publication of the mismatch negativity (MMN) event-related brain potential (ERP) component. The first 10years of research hardly gained any particular attention of the scientific community interested in acoustic perception. Debates on the nature of sensation versus perception were going on, and the technical possibilities to record ERPs, called in general evoked potentials, were very limited. Subtle changes in pure tone frequency or intensity giving rise to the MMN component were first investigated in humans. The background of the theoretical model developed by Risto Näätänen was the orientation reaction model of E.N. Sokolov published in 1963 so that the MMN was seen first as an electrophysiological correlate of auditory change detection. This fundamental ability of the auditory system seen as crucial for survival led to the development of the first animal model of the MMN (Csépe et al. in Clin Neurophysiol 66: 571-578, 1987). Indeed, it was confirmed that the MMN was the brain correlate of subtle changes detected that might alert to potential threats in the environment and direct the behavioral orientation. The investigations performed after 2000 introduced complex models and more sophisticated methods, both in animal and human studies, so that the MMN method was on the way to become a tool on the first place and not the main goal of research. This approach was further strengthened by the increasing number of studies on different clinical populations aiming at future applications. The aim of our review is to describe and redefine what the MMN may reflect in auditory perception and to show why and how this brain correlate of changes in the auditory scene can be used as a valuable tool in cognitive neuroscience research. We refer to publications selectedto underly theargument the MMN cannot be classified anymore as a sign of simple change detection and not all the indicators used to confirm howgenuine theMMN elicited byvariations of tones are valid for those tospeechcontrasts. We provide a fresh view on the broadly used MMN models, provided by some influential publications as well as on the unwritten history of MMN research aiming to give revised picture on what the MMN may truly reflect. We show how the focus and terminology of the MMN research have changed and what kind of misunderstandings and seemingly contradictive results prevent the MMN community to accept a generally usable cognitive model.

Trace amine-associated receptor 1 (TAAR1) agonism for psychosis: a living systematic review and meta-analysis of human and non-human data

Background Trace amine-associated receptor 1 (TAAR1) agonism shows promise for treating psychosis, prompting us to synthesise data from human and non-human studies. Methods We co-produced a living systematic review of controlled studies examining TAAR1 agonists in individuals (with or without psychosis/schizophrenia) and relevant animal models. Two independent reviewers identified studies in multiple electronic databases (until 17.11.2023), extracted data, and assessed risk of bias. Primary outcomes were standardised mean differences (SMD) for overall symptoms in human studies and hyperlocomotion in animal models. We also examined adverse events and neurotransmitter signalling. We synthesised data with random-effects meta-analyses. Results Nine randomised trials provided data for two TAAR1 agonists (ulotaront and ralmitaront), and 15 animal studies for 10 TAAR1 agonists. Ulotaront and ralmitaront demonstrated few differences compared to placebo in improving overall symptoms in adults with acute schizophrenia (N=4 studies, n=1291 participants; SMD=0.15, 95%CI: -0.05, 0.34), and ralmitaront was less efficacious than risperidone (N=1, n=156, SMD=-0.53, 95%CI: -0.86, -0.20). Large placebo response was observed in ulotaront phase-III trials. Limited evidence suggested a relatively benign side-effect profile for TAAR1 agonists, although nausea and sedation were common after a single dose of ulotaront. In animal studies, TAAR1 agonists improved hyperlocomotion compared to control (N=13 studies, k=41 experiments, SMD=1.01, 95%CI: 0.74, 1.27), but seemed less efficacious compared to dopamine D2 receptor antagonists (N=4, k=7, SMD=-0.62, 95%CI: -1.32, 0.08). Limited human and animal data indicated that TAAR1 agonists may regulate presynaptic dopaminergic signalling. Conclusions TAAR1 agonists may be less efficacious than dopamine D2 receptor antagonists already licensed for schizophrenia. The results are preliminary due to the limited number of drugs examined, lack of longer-term data, publication bias, and assay sensitivity concerns in trials associated with large placebo response. Considering their unique mechanism of action, relatively benign side-effect profile and ongoing drug development, further research is warranted. Registration PROSPERO-ID:CRD42023451628.

Synergistic effects of Metformin and Forskolin on oxidative stress induced by diabetes and hepatocellular cancer: an animal study

AimThis study proposed to assess the synergistic effects of Forskolin and Metformin (alone and in combination) on glucose, hematological, liver serum, and oxidative stress parameters in diabetic, healthy, and hepatocellular carcinoma (HCC) induced rats. Materials and methodsEighty male Wistar rats were divided into 10 experimental groups (8 rats for each group), including 1) healthy group, 2) diabetic group, 3) HCC group, 4) diabet+Metformin (300 mg/kg), 5) diabet+Forskolin (100 mg/kg), 6) diabet+Metformin (300 mg/kg) & Forskolin (100 mg/kg), 7) HCC+Metformin (300 mg/kg), 8) HCC+Forskolin (100 mg/kg), 9) HCC+Metformin (300 mg/kg) & Forskolin (100 mg/kg), and 10) healthy group+Metformin (300 mg/kg) & Forskolin (100 mg/kg). The rats were administrated Forskolin/Metformin daily for 8 weeks. Glucose, hematological, and liver serum parameters were measured and compared among the groups. The levels of malondialdehyde (MDA), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), as well as 8-hydroxydeoxyguanosine (8 OHdG) levels, were also measured. ResultsThe average blood glucose reduction in diabetic rats with the Forskolin, Metformin, and Forskolin+ Metformin treatments was 43.5%, 47.1%, and 53.9%, respectively. These reduction values for HCC rats after the treatments were 21.0%, 16.2%, and 23.7%, respectively. For all the diabetic and HCC rats treated with Forskolin/Metformin, the MDA, SOD, and GPx levels showed significant improvement compared with the diabetic and HCC groups (P<0.05). Although the rats treated with Forskolin+Metformin experienced a higher reduction in oxidative stress of blood and urine samples compared to the Forskolin group, the differences between this group and rats treated with Metformin were not significant for all parameters. ConclusionMetformin and Forskolin reduced oxidative stress in diabetic and HCC-induced rats. The results indicated that the combination of agents (Metformin & Forskolin) had greater therapeutic effects than Forskolin alone in reducing glucose levels in diabetic rats. However, the ameliorative effects of combining Metformin and Forskolin on blood and urine oxidative stress were not statistically higher than those of Metformin alone.

May food become medicine - does carp meat have a chance to become a functional food for people with cardiovascular disease?

Abstract Fish consumption is associated with lower risk of cardiovascular disease mortality. The health benefits of fish consumption are attributed to high content of omega-3 polyunsaturated fatty acids (PUFA), especially eicosapentaenoic and docosahexaenoic acid. Animal and human studies have demonstrated that n-3 PUFAs improve the function of the normal and damaged endothelium. It is recommended to eat two servings of fish per week. The aim of the review was to find publications about the nutritional value of carp meat and its possible uses as functional food for patients with cardiovascular disease. A search for open–access original full texts sin PubMed, Google Scholar, Medline Complete database was performed in June 2022. A total of 490 results were found. Eventually 22 articles were included for systematic review. Carp consumption improves plasma lipid profile and therefore it could be considered a functional food. Carp meat is rich in essential amino acids too. The carp culture systems decide about PUFA and protein content in the meat. Carp can be cooked as traditional dishes or carp powder can be added to other dishes to enrich their nutritional value. The recommended method of carp meat preparation to preserve its’ nutritional value is oven baking. Carp meat or carp powder can be used as functional food for patients with cardiovascular diseases.

Progress of preclinical research on induced pluripotent stem cell therapy for acute myocardial infarction.

Induced pluripotent stem cells (iPSCs) are obtained by introducing exogenous genes or adding chemicals to the culture medium to induce somatic cell differentiation. iPSCs have the ability to differentiate into all three embryonic cell lines, similar to embryonic stem cells. iPSCs can differentiate into cardiac muscle cells through two-dimensional differentiation methods such as monolayer cell culture and co-culture, or through embryoid body and scaffold-based three-dimensional differentiation methods. In addition, the process of iPSCs differentiation into cardiac muscle cells also requires activation or inhibition of specific signaling pathways,such as Wnt, BMP, Notch signaling pathways to mimic the development of the heart in vivo. In recent years, cell suspension culture by bioreactors has been able to produce large number of iPSCs derived cardiac muscle cells (iPSC-CMs). Before transplantation it is necessary to purify iPSC-CMs through metabolic regulation or cell sorting to eliminate undifferentiated iPSCs, which may lead to teratoma formation. The transplantation methods for iPSC-CMs are mainly injection of cell suspension and transplantation of cell patches into the infarcted myocardium. Animal studies have shown that transplantation of iPSC-CMs into the infarcted myocardium can improve cardiac function. This article reviews the progress of preclinical studies on iPSC-CMs therapy for acute myocardial infarction and discusses the limitations and challenges of its clinical application to provide references for further clinical research and application.

Animal Fridays in Robinson Crusoe and Its Afterlives

Robinson narrates his rescue of Friday in a way that is reminiscent of the saving of the dog ten pages before: he calls them both ‘poor creatures’ and uses non-verbal communication with Friday at first as he does with his ‘pets’: all are discussed and addressed as his ‘subjects’ and possessions, irrespective of their human or non-human bodies. In a number of Robinsonades, the blurred human-animal boundary is translated in the fact that the role of Friday is taken up by an animal, most often a pet, as is the case with Yann Martel’s Life of Pi, in which the tiger, Richard Parker, is subjugated by Pi in a manner reminiscent of imperial control. Following recent critical work on ‘Animal Crusoes’ in children’s Robinsonades as well as the increased interest in ecocritical, posthuman theories and animal studies, this article focuses on animal comparisons and characters as regards Friday in Defoe’s novel and Life of Pi. It shows that while both texts may depict the subjugation of Friday in the context of colonialism and imperialism, they also participate in the breaking down of the absolute boundaries between humans and non-humans and provide a reflection upon and reevaluation of the nature/culture dichotomy.