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.

Transplantation of human amniotic epithelial cells repairs brachial plexus injury:pathological and biomechanical analyses

A brachial plexus injury model was established in rabbits by stretching the C6 nerve root. Imme- diately after the stretching, a suspension of human amniotic epithelial cells was injected into the injured brachial plexus. The results of tensile mechanical testing of the brachial plexus showed that the tensile elastic limit strain, elastic limit stress, maximum stress, and maximum strain of the injured brachial plexuses were significantly increased at 24 weeks after the injection. The treatment clearly improved the pathological morphology of the injured brachial plexus nerve, as seen by hematoxylin eosin staining, and the functions of the rabbit forepaw were restored. These data indicate that the injection of human amniotic epithelial cells contributed to the repair of brachial plexus injury, and that this technique may transform into current clinical treatment strategies.

Effects of epidermal growth factor on the growth of human gastric cancer cell and the implanted tumor of nude mice

AIM: Epidermal growth factor (EGF) plays an important role in the regulation of gastrointestinal tissue growth and development, and it can stimulate epithelial proliferation, cell differentiation and growth. It has been established that the EGF can promote gastric cytoprotection and ulcer healing. But the potential ability of EGF to regulate the gastric cancer growth is unknown. This study is to investigate the influence of EGF on human gastric cancer cell and the implanted tumor growth of nude mice. METHODS: The cell growth rates of human gastric adenocarcinoma cell lines MKN-28, MKN-45, SGC-7901 and normal human gastric epithelial cells 3T3 were assessed when incubated with recombinant human EGF (rhEGF, 0.05, 0.1, 0.5, 1.0, 10, 50, 100 mg.L(-1)) using MTT method. The cells of MKN-28, MKN-45, SGC-7901 (gastric cancer tissue 1.5mm(3)) were implanted in the BALB/cA nude mice for 10 days.The EGF was given intraperitoneally (15, 30, 60 microg.kg(-1)) for 3 weeks. The body weights of the tumor-bearing animals and their tumor mass were measured afterwards to assess the mitogenic effect of rhEGF in the nude mice. RESULTS: Within the concentration range of 0.05-100mg.L(-1), rhEGF could increase the cell growth of normal 3T3 cells (cell growth rate 100% vs 102.8%, P【0.05), but partially restrain the gastric cancer cell growth. The latter effect was related to cell differentiation. In 15-60 microg/kg rhEGF groups, the mean implanted tumor mass of MKN-28 cell were 1.75 g, 1.91 g, 2.08 g/NS group 1.97 g (P】0.05), the mean tumor mass of SGC-7901 cell were 1.53 g, 1.07 g, 1.20 g/NS group 1.07 g (P】0.05), and for MKN-45 cell, the tumor mass were respectively 1.92 g, 1.29 g, 1.77 /NS group 1.82 g (P】0.05). So rhEGF had no obvious effect on implanted MKN-28, SGC-7901 and MKN-45 tumor growth. CONCLUSION: EGF has no stimulating effect on the human gastric cancer cell growth neither in vitro nor in vivo.

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.

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.

Experimental and clinic-opathologic study on the relationship between transcription factor Egr-1 and esophageal carcinoma

AIM: To observe the growth suppression effect of exogenous introduction of early growth response gene-1 (Egr-1 gene) on esophageal carcinoma tissue as well as on esophageal carcinoma cell line Eca109 and to explore the potential application of Egr-1 gene in gene therapy of tumor. METHODS: Eukaryotic expression vector of PCMV-Egr-1 plasmid was introduced into Eca109 cell line which expressed no Egr-1 protein originally with lipofectamine transfection method. The introduction and expression of PCMV-Egr-1 plasmid into Eca109 cell line was confirmed by G418 selection culture, PCR amplification of neogene contained in the vector, Western blot analysis and immunocytochemical analysis. The cell growth curve, soft agar colony formation rate and tumorigenicity in SCID mice were examined to demonstrate the growth suppression effect of exogenous Egr-1 gene on Eca109 cell line. The Egr-1 mRNA and Egr-1 protein were also detected in 50 surgical specimens of esophageal carcinoma by in situ hybridization and immunohistochemistry. RESULTS: Exogenous Egr-1 gene was introduced successfully into Eca109 cell line and expressed Egr-1 protein stably. The transfected Eca109 cell line grew more slowly than control Eca109 as shown by cell growth curves, the soft agar colony formation rate (4.0% vs 6.9%, P 【 0.01) and the average growth rate of tumor in SCID mice (35.5 +/- 7.6 vs 65.8 +/- 7.6, P 【 0.05). The expression level of Egr-1 mRNA and protein significantly increased in dysplastic epithelia adjacent to cancer rather than in cancer tissues (65.8% vs 20.0% by ISH and 57.9% vs 0.01). CONCLUSION: Exogenous Egr-1 gene shows the strong effect of growth inhibition in Eca109 cell line. Egr-1 in the cancer tissue shows down-regulated expression that supports the inhibited function of Egr-1 in cancer growth and suggests Egr-1 may have an important role in gene therapy of esophageal carcinoma.

Expression of vascular endothelial growth factor and its role in oncogenesis of human gastric carcinoma

AIM: To establish the role of vascular endothelial growth factor (VEGF) in the oncogenesis of human gastric carcinoma more directly. METHODS: The expression of VEGF and its receptor kinase-domain insert containing receptor (KDR) in human gastric cancer tissue were observed by immunohistochemical staining. VEGF levels were manipulated in human gastric cancer cell using eukaryotic expression constructs designed to express the complete VEGF(165) complimentary DNA in either the sense or antisense orientation. The biological changes of the cells were observed in which VEGF was up-regulated or down-regulated. RESULTS: VEGF-positive rate was 50%, and VEGF was mainly localized in the cytoplasm and membrane of the tumor cells, while KDR was mainly located in the membrane of vascular endothelial cells in gastric cancer tissues and peri-cancerous tissue. In 2 cases of 50 specimens, the gastric cancer cells expressed KDR, localized in both the cytoplasm and membrane. Introduction of VEGF(165) antisense into human gastric cancer cells (SGC-7901, immunofluorescence intensity, 31.6%)) resulted in a significant reduction in VEGF-specific messenger RNA and total and cell surface VEGF protein (immunofluorescence intensity, 8.9%) (P【0.05). Conversely, stable integration of VEGF(165) in the sense orientation resulted in an increase in cellular and cell surface VEGF (immunofluorescence intensity, 75.4%) (P【0.05). Lowered VEGF levels were associated with a marked decrease in the growth of nude mouse xenografted tumor (at 33 days postimplantation, tumor volume: 345.40 +/- 136.31 mm3)(P【0.05 vs control SGC-7901 group: 1534.40 +/- 362.88 mm3), whereas up-regulation of VEGF resulted in increased xenografted tumor size (at 33 days postimplantation, tumor volume: 2350.50 +/- 637.70 mm3) (P【0.05 vs control SGC-7901 group). CONCLUSION: This study provides direct evidence that VEGF plays an important role in the oncogenesis of human gastric cancer.

Emerging Human Pluripotent Stem Cell-Based Human–Animal Brain Chimeras for Advancing Disease Modeling and Cell Therapy for Neurological Disorders

Human pluripotent stem cell(hPSC)models provide unprecedented opportunities to study human neurological disorders by recapitulating human-specific disease mechanisms.In particular,hPSC-based human–animal brain chimeras enable the study of human cell pathophysiology in vivo.In chimeric brains,human neural and immune cells can maintain human-specific features,undergo maturation,and functionally integrate into host brains,allowing scientists to study how human cells impact neural circuits and animal behaviors.The emerging human–animal brain chimeras hold promise for modeling human brain cells and their interactions in health and disease,elucidating the disease mechanism from molecular and cellular to circuit and behavioral levels,and testing the efficacy of cell therapy interventions.Here,we discuss recent advances in the generation and applications of using human–animal chimeric brain models for the study of neurological disorders,including disease modeling and cell therapy.

Clinical/Behavioral Monitoring of Rodents and Rabbits Undergoing Scientific Experiments

Background: We currently have international and national guidelines regarding the assessment and monitoring of clinical signs and humane endpoints in animals used in teaching and research, which make the performance of these activities mandatory for any experiment and professional working in this area. Assigning the severity of a research experiment is the result of an analysis of records of observations of the animal’s behavior, and clinical signs. The aim of this study was to describe the importance of carrying out a severity assessment associated with clinical and behavioral monitoring of rodents and rabbits during experimentation to maintain the welfare of these animals undergoing scientific research. Methods: The literature search was carried out using the following terms: “Monitoring”;“Humane endpoints”;“Animal welfare”, “Rodents”;“Rabbits”, and as connectors “and”;“or”, in the following databases: PubMed;LILACS/BIREME and SciELO. Results: A total of 987 articles were identified in the databases, and 20 of these studies were included in this review. Conclusions: Humane endpoint protocols and procedure severity tables are of the utmost importance, both from an ethical point and to refine the results of research conducted on laboratory animals. They should be drawn up jointly by the teams responsible for the project and the maintenance of the animals during the research period, and the data obtained should be published so that the scientific community can have access to it, helping to disseminate these practices, as well as helping to draw up new procedures. Monitoring and evaluating the welfare and clinical condition of animals undergoing scientific research procedures is the responsibility of the professors, researchers, veterinarians, and animal facility coordinators. The Ethics Committee on the Use of Animals must monitor all the activities conducted with the animals, by inspecting the experimental procedures and the physical environment of the laboratory animal facility where the animals are housed.

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.

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.

Exploring the role of N-acetyltransferases in diseases:a focus on N-acetyltransferase 9 in neurodegeneration

Acetyltransferases,required to transfer an acetyl group on protein are highly conserved proteins that play a crucial role in development and disease.Protein acetylation is a common post-translational modification pivotal to basic cellular processes.Close to 80%-90%of proteins are acetylated during translation,which is an irreversible process that affects protein structure,function,life,and localization.In this review,we have discussed the various N-acetyltransferases present in humans,their function,and how they might play a role in diseases.Furthermore,we have focused on N-acetyltransferase 9 and its role in microtubule stability.We have shed light on how N-acetyltransferase 9 and acetylation of proteins can potentially play a role in neurodegenerative diseases.We have specifically discussed the N-acetyltransferase 9-acetylation independent function and regulation of c-Jun N-terminal kinase signaling and microtubule stability during development and neurodegeneration.

Physiological and Molecular Characterization of <i>Malassezia pachydermatis</i>Reveals No Differences between Canines and Their Owners

Introduction: The genus Malassezia comprises 17 species of commensal and pathogenic yeasts of homeotherms animal skin. The most common species are M. furfur, M. globosa, and M. sympodialis in humans and M. pachydermatis in animals. However, some publications have reported potentially serious human infections by M. pachydermatis in individuals with risk factors and the isolation of human species from domestic animals. Given the scarcity of information about their capacity for transmission between hosts and zoonotic potential, the aim of the present study was to physiologically and molecularly characterize Malassezia spp. isolates obtained from canines and their human owners. Materials and Methods: An experimental study was conducted at the Veterinary Clinic of Universidad de Ciencias Aplicadas y Ambientales of Bogotá (Colombia) from July 2015 to December 2016. Phenotypic identification and molecular characterization via the amplification of the 5.8S rDNA- ITS2 and 26S rDNA gene regions, nucleic acid sequencing, and phylogenetic analyses were performed on isolates originating from canines with otitis externa and from the skin of healthy owners compatible with Malassezia spp. Results: Eighty samples were cultured, of which 32 (40%) were suggestive of Malassezia spp. A total of 29 out of 46 (63%) isolates in canines and 3 out of 34 (9%) isolates in humans corresponded entirely with M. pachydermatis. Isolates from the canines and their owners presented similar behavior in biochemical and phospholipase activity tests, 100% molecular sequence identities, and close proximity in the phylogenetic trees. Conclusion: The isolation of M. pachydermatis from humans and their dogs with identity based on biochemical, physiological, molecular, and phylogenetic perspectives indicate the ability of this species to adapt to new hosts and its potential for zoonotic transmission. These findings contribute to knowledge of the ecology of this important fungus in human and veterinary medicine.

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.