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）.

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

AIM To evaluate the antifibrotic effect ofdifferent doses of recombinant human Gamma-Interferon (IFN-γ) intwo rat models of hepaticfibrosis, and to observe its effect on moderatechronic hepatitis B virus fibrosis.METNODS Hepatic fibrosis was successfullyinduced in 150 and 196 rats by subcutaneousinjection of carbon tetrachloride (CCl4) andintraperitoneal injection of dimethylnitrosamine(DMN), respectively. Each of the two modeldose IFN-γ group (15 MU/kg per day, i.m. for 8group (1.67 MU/kg daily, i.m. for 8 weeks).Another group of 10 rats without any treatmentwas used as normal controls. At the end of theexperiment, semi-quantitative histopathologicalscores of inflammation and fibrosis, liver (αsmooth muscle actin (α-SMA) expression level,liver hydroxyl proline content and serumhyaluronic acid levels were compared. And 47medium chronic hepatitis B viral fibrosispatients were studied. They were given IFN-γtreatment, 100MU/day i.m. for the first threemonths and 100MU qod i.m. for the next sixmonths. Semi-quantitative pathological scoresof inflammation and fibrosis and serum hepaticfibrosis indices were compared within the 9months.RESULTS In animal experiment, thepathological fibrosis scores and liver hydroxylproline content were found to be significantlylower in rats treated with different doses of IFN-γ as compared with rats in fibrotic model groupinduced by either CCI4 or DMN, in a dose-dependent manner. For CCI4-induced model,pathological fibrosis scores in high, medium andIow doses IFN-γ groups were 5.10 ± 2.88, 7.70 ±3.53 and 8.00 ± 3.30, respectively, but the scorewas 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-γgroups, 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 scoreswere 6.30±0.48, 8.10 ±2.72 and 8.30 ±2.58, inhigh, medium and Iow doses IFN-γ groups, and12.60 ± 3.57 in fibrotic model group. Hydroxylproline contents were 2.72 ± 0.58, 3.14 ± 0.71and 3.62 ± 1.02, in the three IFN-γ groups, and12.79 ± 1.54 in fibrotic model group. Thedifference was statistically significant(P＜0.01). Serum hepatic fibrosis indicesdecreased significantly in the 47 patients afterIFN-γ treatment (HA: 433.38 ± 373.00 vs 281.57± 220.48; LN: 161.22± 41.02 vs 146.35 ± 44.67;PCⅢ: 192.59 ± 89.95 vs 156.98 ± 49.22; C-Ⅳ:156.30 ± 44.01 vs 139.14 ± 34.47) and thedifferences between the four indices weresignificant (P＜0.05). Thirty-three patientsCONCLUSION All the three doses of IFN-γ areeffective in treating rat liver fibrosis induced byeither CCl4 or DMN, the higher the dose, thebetter the effect. And IFN-γ is effective forpatients with moderate chronic hepatitis B viralfibrosis.

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.

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.

蒙脱石调控肠道菌群研究进展

蒙脱石是一种多用途的铝硅酸盐类黏土,通过表面吸附、静电吸附和分子间作用力,可去除饲料和养殖动物肠道中的真菌毒素、重金属和细菌,被广泛应用于饲料行业。肠道菌群对维持宿主的生长发育、促进营养吸收和协助免疫应答等生理功能发挥方面至关重要。蒙脱石在调控动物肠道菌群方面也有突出作用,蒙脱石散是典型例证。为此本文系统性地梳理蒙脱石在人类、小鼠、畜禽和水产动物应用过程对肠道菌群的影响情况,旨在为蒙脱石调控肠道菌群,改善宿主生理功能和健康养殖提供理论依据。

“贫乏于世”的深意——论海德格尔“动物之思”的起源及其意义

海德格尔的《形而上学的基本概念》并非海德格尔“动物之思”的真正起源,既有国内外研究并未深究这一问题,而且都遗漏了对一部重要作品的考察,此即《康德〈纯粹理性批判〉的现象学阐释》。通过对此书的文本分析,我们可以看清,海德格尔“动物之思”的起源、海德格尔特有的“自由”概念的启动以及海德格尔“康德阐释”的正式开端,三者共同交织于此书中。海德格尔“动物贫乏于世界”命题的深意因而在于:我们可以从这一命题重新思考海德格尔思想的一段关键历程,即海德格尔思想“转向”的开端进程。就此而论,海德格尔的“动物之思”绝非只是海德格尔思想的副产品,而应视为海德格尔思想道路上的一种至深至远的本真之思。