How can we establish animal models of HIV-associated lymphoma?

Human immunodeficiency virus(HIV)infection is strongly associated with a height-ened incidence of lymphomas.To mirror the natural course of human HIV infection,animal models have been developed.These models serve as valuable tools to inves-tigate disease pathobiology,assess antiretroviral and immunomodulatory drugs,ex-plore viral reservoirs,and develop eradication strategies.However,there are currently no validated in vivo models of HIV-associated lymphoma(HAL),hampering progress in this crucial domain,and scant attention has been given to developing animal models dedicated to studying HAL,despite their pivotal role in advancing knowledge.This re-view provides a comprehensive overview of the existing animal models of HAL,which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

Era of the 4D animal model

Revealing the entire dynamics of pathogenesis is critical for understanding,preventing and treating human disease but is limited by systematic clinical sampling.This drawback can be overcome with animal model studies.Recent advances in phenotyping,omics and bioinformatics technologies promote the development of the 4D animal model to simulate and digitally display the spatiotemporal landscapes of phenotypes and molecular dynamics in human diseases and reveal novel targets for diagnosis and therapy.In this commentary,the origin,supporting technologies,content,function and application,and advantages of 4D animal models over clinical studies and traditional animal models,as well as their limitations,are presented.

Serological Survey of Zika Virus in Humans and Animals in Dejiang Prefecture, Guizhou Province,China

Objective The current outbreak of Zika virus(ZIKV)poses a severe threat to human health.Two ZIKV strains were isolated from mosquitoes collected from the Dejiang prefecture in China in 2016,which was the first isolation of ZIKV in nature in China.Methods In this study,serum samples were collected from 366 healthy individuals and 104 animals from Dejiang prefecture in 2017,and the plaque reduction neutralization test(PRNT)was used to evaluate the seroprevalence of ZIKV.Results None of the 366 residents from whom the samples were collected were seropositive for ZIKV.None of the 11 pigs from whom the samples were collected were seropositive for ZIKV,while 1 of 63(1.59%)chickens and 2 of 30(6.67%)sheep were seropositive for ZIKV.Conclusions The extremely low seropositivity rate of ZIKV antibodies in animals in the Dejiang prefecture,Guizhou province in this study indicates that ZIKV can infect animals;however,there is a low risk of ZIKV circulating in the local population.

Production of human polyclonal antibodies by transgenic animals

Polyclonal antibodies collected from the blood of animals and humans experimentally immunised or spontaneously immunised respectively can be injected into patients to protect them against pathogens, toxins, tumours etc. This approach is severely limited by the availability of human polyclonal antibodies of interest. Moreover, polyclonal antibodies from animals are recognised as antigens by patients and are thus rapidly rejected and inactivated. To circumvent this problem, animals (essentially rabbits, chicken, pigs and cows) are being genetically engineered. Their immunoglobulin genes are being inactivated and the corresponding human immunoglobulin genes are being transferred to them. These animals will be immunized and it is expected that large amounts of pure human polyclonal antibodies will be extracted from their blood to be administered to patients. The possible acceptability problem of this approach is under a case study of the European Union Pegasus project.

Infection of <i>Toxoplasma gondii</i>in Humans and Livestock Animals: An Emerging Silent Threat for Bangladesh

Toxoplasma gondii is an intracellular, zoonotic protozoan parasite that causes toxoplasmosis. It can potentially infect almost all mammalian and avian hosts including one-third of the human population world-wide. The major target group of the parasite includes immunocompromised patients (e.g. AIDS, cancer, organ transplantation) and fetus bearing pregnant women where it develops toxoplasmic encephalitis, myocarditis, chorioretinitis and abnormal fetal brain development or stillbirths respectively. In this review, we have presented the current status of T. gondii infection in livestock animals and human population in Bangladesh to assess the country-wide relative risk. Although exact prevalence is difficult to predict due to the scarcity of data, nevertheless existing literature suggests that 16% - 39% humans and 8% - 70% domestic animals are infected with T. gondii, which implies Bangladeshi population is at high risk of toxoplasmosis. Furthermore, we have proposed a potential area of research to decipher the genetic diversity and transmission routes of T. gondii infection into Bangladeshi population.

Review of human-animal interactions and their impact on animal productivity and welfare

Humans and animals are in regular and at times close contact in modern intensive farming systems.The quality of human-animal interactions can have a profound impact on the productivity and welfare of farm animals.Interactions by humans may be neutral,positive or negative in nature.Regular pleasant contact with humans may result in desirable alterations in the physiology,behaviour,health and productivity of farm animals.On the contrary,animals that were subjected to aversive human contact were highly fearful of humans and their growth and reproductive performance could be compromised.Farm animals are particularly sensitive to human stimulation that occurs early in life,while many systems of the animals are still developing.This may have long-lasting impact and could possibly modify their genetic potential.The question as to how human contact can have a positive impact on responses to stressors,and productivity is not well understood.Recent work in our laboratory suggested that pleasant human contact may alter ability to tolerate various stressors through enhanced heat shock protein（hsp） 70 expression.The induction of hsp is often associated with increased tolerance to environmental stressors and disease resistance in animals.The attitude and consequent behaviour of stockpeople affect the animals＇ fear of human which eventually influence animals＇ productivity and welfare.Other than attitude and behaviour,technical skills,knowledge,job motivation,commitment and job satisfaction are prerequisites for high job performance.

Suppression of Radioactive Strontium Absorption by Sodium Alginate in Animals and Human Subjects

The effect of 23 sodium alginate preparations from different species of algae (Sargassum sp.) and kelp (Laminaria sp.) on reducing the absorption of strontium was studied in detail. A pilot production procedure has been established. Na alginate from S. siliquastrum was proven to be a potent agent for reducing Sr absorption, with high efficiency and virtually no toxicity. It reduced the body burden of strontium 3.3-4.2 fold in rats. Strontium absorption in human subjects was reduced by 78% ( ±8.9) or completely suppressed the increase of serum Sr at 2 h after ingestion of stable Sr in volunteers and decrease 24 h urine Sr to similar extent. No undesirable effects on gastrointestinal function was observed nor were Ca, Fe, Cu and Zn metabolism changed, both in the animal experiments and in human. It was concluded that alginate preparations derived from Sargassum species are a suitable antidote against radiostrontium absorption on a long-term basis, when added to bread at a 6% level. In cases of emergency, an alginate syrup preparation appears to be more suitable because of its rapid action.

Establishment of a humanized ST6GAL1 mouse model for influenza research

Background:This study aimed to construct and characterize a humanized influenza mouse model expressing hST6GAL1.Methods:Humanized fragments,consisting of the endothelial cell-specific K18 promoter,human ST6GAL1-encoding gene,and luciferase gene,were microinjected into the fertilized eggs of mice.The manipulated embryos were transferred into the oviducts of pseudopregnant female mice.The offspring were identified using PCR.Mice exhibiting elevated expression of the hST6GAL1 gene were selectively bred for propagation,and in vivo analysis was performed for screening.Expression of the humanized gene was tested by performing immunohistochemical(IHC)analysis.Hematologic and biochemical analyses using the whole blood and serum of humanized hST6GAL1 mice were performed.Results:Successful integration of the human ST6GAL1 gene into the mouse genome led to the overexpression of human SiaT ST6GAL1.Seven mice were identified as carrying copies of the humanized gene,and the in vivo analysis indicated that hST6GAL1gene expression in positive mice mirrored influenza virus infection characteristics.The IHC results revealed that hST6GAL1 was expressed in the lungs of humanized mice.Moreover,the hematologic and biochemical parameters of the positive mice were within the normal range.Conclusion:A humanized influenza mouse model expressing the hST6GAL1 gene was successfully established and characterized.

Human and animal sarcocystosis in Malaysia: A review

Sarcocystosis is a zoonotic disease caused by a coccidian intracellular protozoan parasite of the genus Sarcocystis. More than 200 Sarcocystis species have been recorded and the parasites are found in mammals, birds and reptiles. They require two hosts to complete their life cycle. In Malaysia, sarcocystosis was reported as a potential emerging food and water-borne disease after a series of large outbreak of human infections. There was not enough attention given before even though it was reported in both humans and animals.The first human case of invasive muscular sarcocystosis among local Malaysian was reported in 1975. Besides, a retrospective autopsy examination on 100 tongues revealed21% positive cases. On top of that, a sero-epidemiological survey conducted in 243 subjects in West Malaysia showed that 19.7% had Sarcocystis antibodies. The clinical symptoms of muscular sarcocystosis were first described comprehensively in 1999.Meanwhile, many types of animals including livestock were found harbor the sarcocysts in their tissue. The first case of human intestinal sarcocystosis was reported in 2014. This review indicates that human sarcocystosis is currently endemic in Malaysia and parallel to that reported in animals. However, more studies and investigations need to be conducted since the source of human infection remains unknown.

Selenium metabolism in animals and humans

The main purpose of this paper is to point out the differences in the metabolism of Se between animals and humans. This is not to imply that the work with animals is not applicable to human because the use of animals in Se research has greatly assisted in understanding Se metabolism in human subjects. It is fair to conclude that until results are confirmed in humans it is risky to draw conclusions on Se metabolism in human based solely on animal data. Although animals have provided some extremely useful information on metabolism of Se,there is convincing evidence to indicate that some features of Se metabolism are unique to human. A few examples were given to support this contention.

Ciprofloxacin Cardiotoxicity and Hepatotoxicity in Humans and Animals

Ciprofloxacin is generally well tolerated;the most common adverse effects include gastro intestinal tract, central nervous system and hematological system effects. Recently rising cases of Ciprofloxacin associated toxicity have been reported. Experiment using animal models and clinical experience showed that Ciprofloxacin induced cardiotoxicity is marked by increase QT and QTC interval and prolonged action potential duration. This increases the risk of arrhythmia (tosarde de pointes). Ciprofloxacin induced cardiotoxic effect could be associated with blocking cardiac voltage—gated potassium channels particularly the rapid component (IKr) of the delayed rectifier potassium current. Drug interaction with inhibitors of Cytochrome P450 (CYP) mediated metabolism could be one of the underlying mechanisms. Several cases of Ciprofloxacin induced hepatoxicity have been also reported. These were characterized by extensive hepatocellular necrosis, mixed inflammatory infiltrate and abundant esinophils in the liver. Elevated liver enzymes which include serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and gramma-glutamyltranferase and prolong prothrobin time were reported. The hepatotoxic effect of Ciprofloxacin as reported could be due to oxidative stress induced in the liver by Ciprofloxacin through the generation of oxidative radicals leading to depletion of protein content in hepatocytes as a consequence of nucleic acids diminution and DNA damage. This may lead to significant decrease in the number and degeneration in mitochondria which is responsible for energy supply. Conclusion: Ciprofloxacin induced cardiotoxicity and hepatotoxicity is relatively low in humans but patients’ liver and cardiac function may be considered before Ciprofloxacin use.

Animal model of repetitive mild traumatic brain injury for human traumatic axonal injury and chronic traumatic encephalopathy

Chronic traumatic encephalopathy（CTE）is a chronic neurodegenerative disease featured with tauopathy.CTE is tightly related with repetitive mild traumatic brain injury（m TBI）,which is interchangeably known as concussion（Mc Kee et al.,2009,2013）.This disease is differentiated by neuropathological features from other neurological diseases that involve tau protein aggregation and tangle formation abnormalities like Alzheimer＇s disease （AD）, frontotemporal dementia, and Parkinson- ism linked to chromosome 17 （FTDP-17）.

Research on the Humanization of the Animal Protagonist in The Call of the Wild

Jack London was one of the outstanding American writers in the late nineteenth and early twentieth century. The Call of the Wild which was based on the Klondike Gold Rush, was the most famous and popular one in China. These years, lots of scholars have discussed it from various aspects, such as the contents, the themes, the writing styles and its characters. In this short novel, the protagonist Buck is humanized by the author. He is endowed with lots of human qualities, such as loyalty, brave, self-esteem, intelligence and so on. What are the reasons of humanization of the dog protagonist.？ Finding out the reasons could help us understand this novel better and it may offer some references for the research on Jack London＇ s animal novels.

Animal experiment and clinical study of effect of gamma-interferon on hepatic fibrosis

AIM: To evaluate the antifibrotic effect of different doses of recombinant human Gamma-Interferon (IFN-gamma) in two rat models of hepatic fibrosis, and to observe its effect on moderate chronic hepatitis B virus fibrosis. METHODS: Hepatic fibrosis was successfully induced in 150 and 196 rats by subcutaneous injection of carbon tetrachloride (CCl4) and intraperitoneal injection of dimethylnitrosamine (DMN), respectively. Each of the two model groups was divided into: (1) fibrotic model group; (2) colchicine treatment group (0.1 mg/kg/day, gastrogavage for 8 weeks); (3) high-dose IFN-gamma group (15 MU/kg per day, i.m. for 8 weeks); (4) medium-dose IFN-gamma group (5 MU/kg daily, i.m. for 8 weeks); and (5) Y low-dose IFN-gamma group (1.67 MU/kg daily, i.m. for 8 weeks). Another group of 10 rats without any treatment was used as normal controls. At the end of the experiment, semi-quantitative histopathological scores of inflammation and fibrosis, liver alpha smooth muscle actin (alpha-SMA) expression level, liver hydroxyl proline content and serum hyaluronic acid levels were compared. And 47 medium chronic hepatitis B viral fibrosis patients were studied. They were given IFN-gamma treatment, 100 MU/day i.m. for the first three months and 100 MU qod i.m. for the next six months. Semi-quantitative pathological scores of inflammation and fibrosis and serum hepatic fibrosis indices were compared within the 9 months. RESULTS: In animal experiment, the pathological fibrosis scores and liver hydroxyl proline content were found to be significantly lower in rats treated with different doses of IFN-gamma as compared with rats in fibrotic model group induced by either CCl4 or DMN, in a dose-dependent manner. For CCl4-induced model, pathological fibrosis scores in high, medium and low doses IFN-gamma groups were 5.10 +/- 2.88, 7.70 +/- 3.53 and 8.00 +/- 3.30, respectively, but the score was 14.60 +/- 7.82 in fibrotic model group. Hydroxyl proline contents were 2.83 +/- 1.18, 3.59 +/- 1.22 and 4.80 +/- 1.62, in the three IFN-gamma groups, and 10.01 +/- 3.23 in fibrotic model group. The difference was statistically significant (P【0.01). Similar results were found in DMN-induced model. Pathological fibrosis scores were 6.30 +/- 0.48, 8.10 +/- 2.72 and 8.30 +/- 2.58, in high, medium and low doses IFN-gamma groups, and 12.60 +/- 3.57 in fibrotic model group. Hydroxyl proline contents were 2.72 +/- 0.58, 3.14 +/- 0.71 and 3.62 +/- 1.02, in the three IFN-gamma groups, and 12.79 +/- 1.54 in fibrotic model group. The difference was statistically significant (P【0.01).Serum hepatic fibrosis indices decreased significantly in the 47 patients after IFN-gamma treatment (HA: 433.38 +/- 373.00 vs 281.57 +/- 220.48; LN: 161.22 +/- 41.02 vs 146 +/- 35 +/- 44. 67; PC III: 192.59 +/- 89.95 vs 156.98 +/- 49.22; C-I: 156.30 +/- 44.01 vs 139.14 +/- 34.47) and the differences between the four indices were significant (P 【0.05). Thirty-three patients received two liver biopsies, one before and one after IFN-gamma treatment. In thirty of 33 patients IFN-gamma had better effects according to semi-quantitative pathological scores (8.40 +/- 5.83 vs 5.30 +/- 4.05, P【0.05). CONCLUSION: All the three doses of IFN-gamma are effective in treating rat liver fibrosis induced by either CCl4 or DMN, the higher the dose, the better the effect. And IFN-gamma is effective for patients with moderate chronic hepatitis B viral fibrosis.

Role of gut microbiota in ischemic stroke:A narrative review of human and animal studies

The high incidence,mortality,and disability associated with ischemic stroke pose a significant threat to human health.The intestinal microbiota significantly influences the onset,progression,and prognosis of ischemic stroke.Gut flora plays a pivotal role in brain-gut interactions.The reflection of changes in the gut and brain caused by gut microbes faciltates the investigation of early warning biomarkers and potential therapeutic targets for ischemic stroke.In this narrative review of the relationship between gut microbiota and ischemic stroke,we primarily discuss three topics,grounded in real-world human and animal studies.First,we examined the relationship between ischemic stroke and intestinal microbiota and its metabolites,delineate the overall characteristics of intestinal microbiota dysregulation in ischemic stroke,and assess the potential clinical value,prevailing research controversies,and unique phenomena of intestinal microbiota metabolites such as trimethylamine N-oxide and short-chain fatty acids in ischemic stroke.Second,we explored the potential communication pathways between intestinal flora and ischemic stroke based on the brain-gut axis,encompassing metabolic pathways,immune pathways,and neural pathways.Finally,we encapsulated the factors influencing the severity of ischemic stroke via intestinal flora,the pharmacological and nonpharmacological interventions that modulate intestinal flora in treating ischemic stroke,and the current research landscape of intestinal flora in the context of ischemic stroke sequelae.

Electroencephalography studies of hypoxic ischemia in fetal and neonatal animal models

Alongside clinical achievements,experiments conducted on animal models (including primate or non-primate) have been effective in the understanding of various pathophysiological aspects of perinatal hypoxic/ ischemic encephalopathy (HIE).Due to the reasonably fair degree of flexibility with experiments,most of the research around HIE in the literature has been largely concerned with the neurodevelopmental outcome or how the frequency and duration of HI seizures could relate to the severity of perinatal brain injury,following HI insult.This survey concentrates on how EEG experimental studies using asphyxiated animal models (in rodents,piglets,sheep and non-human primate monkeys) provide a unique opportunity to examine from the exact time of HI event to help gain insights into HIE where human studies become difficult.

Why Does Personalism Turn Towards Animal Ethics？

The intellectual heritage of modernity needs rethinking. It is marked by radical humanism and implied by the ideas of Descartes and Kant above all, which introduces an unbridgeable gap between animals and human persons （nonhuman and human animals）. Intuitive sensibility to the question of the welfare of nonhuman animals meets a theoretical ally in the rapidly growing knowledge on their subjectivity and makes us pose a questions about their ontological status. This context arouses a possibility of a turn to personalist ethics, yet not to its anthropocentric version implied by Kant, but to personalism conceived of as an instance of value ethics as exemplified by Antonio Rosmini and Karol Wojtyta （John Paul II）.

Analysis of the figure of speech in Animal farm

George Orwell＇s Animal farm is a satire on human nature. By severe and vivid satiric techniques such as irony, exaggeration, similes and metaphors, Orwell demonstrates that selfishness, lust for power and corruption would lead to the disillusionment of human＇s pursuit of freedom and equality in a classless society.

Language-Trained Animals: A Window to the “Black Box”

Animals have to process quantity of information in order to take decisions and adapt their behaviors to their physical and social environment. They have to remember previous events (learning), to cope with their internal (motivational and emotional) states and to display flexible behavioral responses. From a human point of view it is quite impossible to access all those information, not only because of the sensorial channels used that can vary but also because all the processing phase occurs in the “black box” and non-human animals are not able to express verbally what they think, feel or want. Though useful information might lie in the “collected data” (animal mind), extracting them into insightful knowledge with human-accessible form (clear meaning, no interpretation) presents a demanding and sophisticated undertaking. Several scientists decided to trained different individuals from several species (apes, dolphins, grey parrots, dogs) in order to teach them a new communicative system that they could share with us. Here, the different studies (techniques and species used) are presented, their constrains but also the main findings.

Refining Animal Models to Enhance Animal Welfare

The use of animals in research will be necessary for scientific advances in the basic and biomedical sciences for the foreseeable future.As we learn more about the ability of animals to experience pain,suffering,and distress,and particularly for mammals,it becomes the responsibility of scientists,institutions,animal caregivers,and veterinarians to seek ways to improve the lives of research animals and refine their care and use.Refinement is one of the three R's emphasized by Russell and Burch,and refers to modification of procedures to minimise the potential for pain,suffering and distress.It may also refer to procedures used to enhance animal comfort.This paper summarizes considerations for refinements in research animal.