Animal-derived Pathogens Research Articles

A Prediction Method for Animal-Derived Drug Resistance Trend Using a Grey-BP Neural Network Combination Model.

There is an increasing drug resistance of animal-derived pathogens, seriously posing a huge threat to the health of animals and humans. Traditional drug resistance testing methods are expensive, have low efficiency, and are time-consuming, making it difficult to evaluate overall drug resistance. To develop a better approach to detect drug resistance, a small sample of Escherichia coli resistance data from 2003 to 2014 in Chengdu, Sichuan Province was used, and multiple regression interpolation was applied to impute missing data based on the time series. Next, cluster analysis was used to classify anti-E. coli drugs. According to the classification results, a GM(1,1)-BP model was selected to analyze the changes in the drug resistance of E. coli, and a drug resistance prediction system was constructed based on the GM(1,1)-BP Neural Network model. The GM(1,1)-BP Neural Network model showed a good prediction effect using a small sample of drug resistance data, with a determination coefficient R2 of 0.7830 and an RMSE of only 0.0527. This model can be applied for the prediction of drug resistance trends of other animal-derived pathogenic bacteria, and provides the scientific and technical means for the effective assessment of bacterial resistance.

Antimicrobial Resistance Risk Assessment Models and Database System for Animal-Derived Pathogens.

(1) Background: The high use of antibiotics has made the issue of antimicrobial resistance (AMR) increasingly serious, which poses a substantial threat to the health of animals and humans. However, there remains a certain gap in the AMR system and risk assessment models between China and the advanced world level. Therefore, this paper aims to provide advanced means for the monitoring of antibiotic use and AMR data, and take piglets as an example to evaluate the risk and highlight the seriousness of AMR in China. (2) Methods: Based on the principal component analysis method, a drug resistance index model of anti-E. coli drugs was established to evaluate the antibiotic risk status in China. Additionally, based on the second-order Monte Carlo methods, a disease risk assessment model for piglets was established to predict the probability of E. coli disease within 30 days of taking florfenicol. Finally, a browser/server architecture-based visualization database system for animal-derived pathogens was developed. (3) Results: The risk of E. coli in the main area was assessed and Hohhot was the highest risk area in China. Compared with the true disease risk probability of 4.1%, the result of the disease risk assessment model is 7.174%, and the absolute error was 3.074%. Conclusions: Taking E. coli as an example, this paper provides an innovative method for rapid and accurate risk assessment of drug resistance. Additionally, the established system and assessment models have potential value for the monitoring and evaluating AMR, highlight the seriousness of antimicrobial resistance, advocate the prudent use of antibiotics, and ensure the safety of animal-derived foods and human health.

Influences of Xeno-Free Media on Mesenchymal Stem Cell Expansion for Clinical Application.

Mesenchymal stem/stromal cells (MSCs) are multipotent somatic stem/progenitor cells that can be isolated from various tissues and have attracted increasing attention from the scientific community. This is due to MSCs showing great potential for incurable disease treatment, and most applications of MSCs involve tissue degeneration and treatment of immune- and inflammation-mediated diseases. Conventional MSC cultures contain fetal bovine serum (FBS), which is a common supplement for cell development but is also a risk factor for exposure to animal-derived pathogens. To avoid the risks resulting from the xenogeneic origin and animal-derived pathogens of FBS, xeno-free media have been developed and commercialized to satisfy MSC expansion demands for human clinical applications. This review summarized and provided an overview of xeno-free media that are currently used for MSC expansion. Additionally, we discussed the influences of different xeno-free media on MSC biology with particular regard to cell morphology, surface marker expression, proliferation, differentiation and immunomodulation. The xeno-free media can be serum-free and xeno-free media or media supplemented with some human-originating substances, such as human serum, human platelet lysates, human umbilical cord serum/plasma, or human plasma-derived supplements for cell culture medium. These media have capacity to maintain a spindle-shaped morphology, the expression of typical surface markers, and the capacity of multipotent differentiation and immunomodulation of MSCs. Xeno-free media showed potential for safe use for human clinical treatment. However, the influences of these xeno-free media on MSCs are various and any xeno-free medium should be examined prior to being used for MSC cultures.

Plant Factories for the Production of Monoclonal Antibodies.

Like animal cells, plant cells bear mechanisms for protein synthesis and posttranslational modification (glycosylation and phosphorylation) that allow them to be seriously considered as factories for therapeutic proteins, including antibodies, with the development of biotechnology. The plant platform for monoclonal antibody production is an attractive approach due to its flexibility, speed, scalability, low cost of production, and lack of contamination risk from animal-derived pathogens. Contemporary production approaches for therapeutic proteins rely on transgenic plants that are obtained via the stable transformation of plant cells as well as the transient (temporary) expression of foreign proteins. In this review, we discuss present-day approaches for monoclonal antibody production in plants (MAPP), features of carbohydrate composition, and methods for the humanization of the MAPP carbohydrate profile. MAPPs that have successfully passed preclinical studies and may be promising for use in clinical practice are presented here. Perspectives on using MAPPs are determined by analyzing their economic benefits and production rates, which are especially important in personalized cancer therapy as well as in cases of bioterrorism and pandemics.

Plasma Polymer-Coated Contact Lenses for the Culture and Transfer of Corneal Epithelial Cells in the Treatment of Limbal Stem Cell Deficiency

Extensive damage to the limbal region of the cornea leads to a severe form of corneal blindness termed as limbal stem cell deficiency (LSCD). Whereas most cases of corneal opacity can be treated with full thickness corneal transplants, LSCD requires stem cell transplantation for successful ocular surface reconstruction. Current treatments for LSCD using limbal stem cell transplantation involve the use of murine NIH 3T3 cells and human amniotic membranes as culture substrates, which pose the threat of transmission of animal-derived pathogens and donor tissue-derived cryptic infections. In this study, we aimed to produce surface modified therapeutic contact lenses for the culture and delivery of corneal epithelial cells for the treatment of LSCD. This approach avoids the possibility of suture-related complications and is completely synthetic. We used plasma polymerization to deposit acid functional groups onto the lenses at various concentrations. Each surface was tested for its suitability to promote corneal epithelial cell adhesion, proliferation, retention of stem cells, and differentiation and found that acid-based chemistries promoted better cell adhesion and proliferation. We also found that the lenses coated with a higher percentage of acid functional groups resulted in a higher number of cells transferred onto the corneal wound bed in rabbit models of LSCD. Immunohistochemistry of the recipient cornea confirmed the presence of autologous, transplanted 5-bromo-2'-deoxyuridine (BrdU)-labeled cells. Hematoxylin staining has also revealed the presence of a stratified epithelium at 26 days post-transplantation. This study provides the first evidence for in vivo transfer and survival of cells transplanted from a contact lens to the wounded corneal surface. It also proposes the possibility of using plasma polymer-coated contact lenses with high acid functional groups as substrates for the culture and transfer of limbal cells in the treatment of LSCD.

Feeder-Free Generation and Long-Term Culture of Human Induced Pluripotent Stem Cells Using Pericellular Matrix of Decidua Derived Mesenchymal Cells

Human ES cells (hESCs) and human induced pluripotent stem cells (hiPSCs) are usually generated and maintained on living feeder cells like mouse embryonic fibroblasts or on a cell-free substrate like Matrigel. For clinical applications, a quality-controlled, xenobiotic-free culture system is required to minimize risks from contaminating animal-derived pathogens and immunogens. We previously reported that the pericellular matrix of decidua-derived mesenchymal cells (PCM-DM) is an ideal human-derived substrate on which to maintain hiPSCs/hESCs. In this study, we examined whether PCM-DM could be used for the generation and long-term stable maintenance of hiPSCs. Decidua-derived mesenchymal cells (DMCs) were reprogrammed by the retroviral transduction of four factors (OCT4, SOX2, KLF4, c-MYC) and cultured on PCM-DM. The established hiPSC clones expressed alkaline phosphatase, hESC-specific genes and cell-surface markers, and differentiated into three germ layers in vitro and in vivo. At over 20 passages, the hiPSCs cultured on PCM-DM held the same cellular properties with genome integrity as those at early passages. Global gene expression analysis showed that the GDF3, FGF4, UTF1, and XIST expression levels varied during culture, and GATA6 was highly expressed under our culture conditions; however, these gene expressions did not affect the cells’ pluripotency. PCM-DM can be conveniently prepared from DMCs, which have a high proliferative potential. Our findings indicate that PCM-DM is a versatile and practical human-derived substrate that can be used for the feeder-cell-free generation and long-term stable maintenance of hiPSCs.

Rapid two-step synthesis of mitrin from heparosan: a replacement for heparin.

We have engineered a two-step enzymatic synthesis of Mitrin which is a more potent and homogeneous anticoagulant than the current animal-derived heparin. This engineered heparin may have advantages of being free from animal-derived pathogens and may also have reduced side effects such as heparin induced thrombocytopenia. This approach can also be extended to tailor heparin-based drugs with improved therapeutic characteristics to treat other disorders or infections in which heparin-like molecules play a major role.

Infection in xenotransplantation.

Advances in transplantation immunology have enhanced the possibility of xenotransplantation as a therapeutic option for end-stage organ failure. The potential spread of animal-derived pathogens to the recipient and to the general population, termed "xenosis," is a potential complication of interspecies transplantation. Recognition of such novel infections may be complicated by infections due to altered microbiologic behavior and clinical symptomatology of these organisms, particularly in the immunocompromised xenograft recipient. Particular concern exists over the activation of latent viruses, including retroviruses, from xenograft tissues. Based on experience with human allogeneic transplantation, those pathogens considered most likely to cause human disease can be excluded prospectively from herds of animals developed for organ donation. Research is needed into the activation and behavior of retroviruses and other potential pathogens in xenotransplantation. Xenotransplantation may also provide unique opportunities not only for the care of patients with organ failure, but in the therapy of individuals with chronic infections to which the xenograft may be resistant. Clinical protocols must be developed so as to enhance the safety of the recipient and of the community-at-large.

Potential risks of viral infections in xenotransplantation

The shortage of cadaveric human organs for transplantation may, be alleviated by the use of xenografts as a therapeutic option for end-stage organ failure. Successful attempts have been made to prevent rejection of xenograft tissues in humans. The potential spread of animal-derived pathogens to the xenograft recipient is a complication of xenotransplantation, which must be addressed. This can be complicated further by, the presence of new pathogens, new clinical syndromes, and altered behaviour of these organisms in the immunocompromised recipient. There is concern over the possible activation of latent viruses, including retroviruses, from xenograft tissues. This paper discusses the possible dangers of transmission of animal viruses to humans via xenotransplantation.