scholarly journals In vivo administration of anti-HIV hyper-immune eggs induces anti-anti-idiotypic antibodies against HIV gp120 peptides (fragments 308-331 and 421-438) and against HIV gp41 peptide (fragment 579-601) which have demonstrable protective capacity

2021 ◽  
Author(s):  
Angel Justiz-Vaillant ◽  
Belkis Ferrer-Cosme ◽  
Monica Fisher Smikle ◽  
Oliver Pérez
Keyword(s):  
Immune Responses ◽  
Hiv Infections ◽  
Egg Yolk ◽  
Laboratory Animals ◽  
Future Research ◽  
Protective Capacity ◽  
Antigen Binding Site ◽  
Hiv Antigen ◽  
Gp41 Peptide

AbstractIsolation of antibodies from the egg yolk of chickens is of particular interest as a source of specific antibodies for oral administration to prevent infections and use them as immunodiagnostic reagents. The use of birds in antibody production results in a reduction in the use of laboratory animals. Immunized chickens produce larger quantities of antibodies (2000 mg IgY/month) than rodents (200 mg IgG/month) in the laboratory. According to Jerne’s network theory, it is possible to produce an antibody against the antigen-binding site of another antibody. This study assessed the hypothesis that immunization with viral peptides (immunogens) could provide a potent immune response that could be evaluated in chicken eggs. Human immunodeficiency virus 1(HIV-1) is used as an immunogen. The second hypothesis was that an orally administered antibody stimulates the production of a complementary antibody, the so-called anti-idiotypic antibody, which can potentially be therapeutical. This study reports and analyzes the use of eggs as therapeutic agents. We wanted to test the hypothesis that feeding chicks with hyperimmune eggs stimulates the production of anti-anti-idiotypic antibodies that neutralize the original HIV antigen fragments 308-331 or 421-438 of gp120 or fragment 579-601 of gp41. Future research could entail an anti-idiotype strategy for prophylactic vaccines. It is vital to note that it may need an anti-idiotype response to prime immunity against an HIV viral epitope, which may be used as a secondary element. The use of anti-idiotype immune responses in infected individuals may shift the balance of the immune system, allowing the organism to manage HIV infection. Therefore, it may be an avenue for immunotherapy to improve the fight against HIV infections. However, more studies and clinical trials are required to demonstrate similar human immune responses as observed in birds.

Combination of Mechanical and Chemical Methods Improves Gene Delivery in Cell-based HIV Vaccines

2019 ◽  
Vol 16 (9) ◽  
pp. 818-828
Author(s):  
Sepehr Soleymani ◽  
Amin Hadi ◽  
Fatemeh Asgari ◽  
Nooshin Haghighipour ◽  
Azam Bolhassani
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Hiv Infections ◽  
Cyclic Stretch ◽  
Hiv Antigen ◽  
Gp120 Subunit ◽  
Hiv 1

Objective: Novel vaccination approaches are required to control human immunodeficiency virus (HIV) infections. The membrane proximal external region (MPER) of Env gp41 subunit and the V3/glycans of Env gp120 subunit were known as potential antigenic targets for anti-HIV-1 vaccines. In this study, we prepared the modified dendritic cells (DCs) and mesenchymal stem cells (MSCs) with HIV-1 MPER-V3 gene using mechanical and chemical approaches. Methods: At first, MPER-V3 fusion DNA delivery was optimized in dendritic cells (DCs) and mesenchymal stem cells (MSCs) using three mechanical (i.e., uniaxial cyclic stretch, equiaxial cyclic stretch and shear stress bioreactors), and two chemical (i.e., TurboFect or Lipofectamine) methods. Next, the modified DCs and MSCs with MPER-V3 antigen were compared to induce immune responses in vivo. Results: Our data showed that the combination of equiaxial cyclic stretch loading and lipofectamine twice with 48 h intervals increased the efficiency of transfection about 60.21 ± 1.05 % and 65.06 ± 0.09 % for MSCs and DCs, respectively. Moreover, DCs and MSCs transfected with MPER-V3 DNA in heterologous DC or MSC prime/ peptide boost immunizations induced high levels of IgG2a, IgG2b, IFN-γ and IL-10 directed toward Th1 responses as well as an increased level of Granzyme B. Indeed, the modified MSCs and DCs with MPER-V3 DNA could significantly enhance the MPER/V3-specific T-cell responses compared to MPER/V3 peptide immunization. Conclusion: These findings showed that the modified MSC-based immunization could elicit effective immune responses against HIV antigen similar to the modified DC-based immunization.

scholarly journals The Utility of Grimace Scales for Practical Pain Assessment in Laboratory Animals

Animals ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1838 ◽  
Author(s):  
Daniel Mota-Rojas ◽  
Adriana Olmos-Hernández ◽  
Antonio Verduzco-Mendoza ◽  
Elein Hernández ◽  
Julio Martínez-Burnes ◽  
...  
Keyword(s):  
Facial Expressions ◽  
Pain Assessment ◽  
Clinical Laboratory ◽  
Laboratory Animals ◽  
Future Research ◽  
Clinical Pain ◽  
Animal Medicine ◽  
Assessment Techniques ◽  
Barriers To Implementation

Animals’ facial expressions are widely used as a readout for emotion. Scientific interest in the facial expressions of laboratory animals has centered primarily on negative experiences, such as pain, experienced as a result of scientific research procedures. Recent attempts to standardize evaluation of facial expressions associated with pain in laboratory animals has culminated in the development of “grimace scales”. The prevention or relief of pain in laboratory animals is a fundamental requirement for in vivo research to satisfy community expectations. However, to date it appears that the grimace scales have not seen widespread implementation as clinical pain assessment techniques in biomedical research. In this review, we discuss some of the barriers to implementation of the scales in clinical laboratory animal medicine, progress made in automation of collection, and suggest avenues for future research.

scholarly journals The Utility of Grimace Scales for Practical Pain Assessment in Laboratory Animals

2020 ◽  
Author(s):  
Daniel Mota-Rojas ◽  
Adriana Olmos-Hernández ◽  
Antonio Verduzco-Mendozab ◽  
Elein Hernández ◽  
Julio Martínez-Burnes ◽  
...  
Keyword(s):  
Facial Expressions ◽  
Pain Assessment ◽  
Clinical Laboratory ◽  
Laboratory Animals ◽  
Future Research ◽  
Clinical Pain ◽  
Animal Medicine ◽  
Assessment Techniques ◽  
Barriers To Implementation

Animals’ facial expressions have been widely used as a readout for emotion. Scientific interest in the facial expressions of laboratory animals has centered primarily on negative experiences, such as pain, experienced as a result of scientific research procedures. Recent attempts to standardize evaluation of facial expressions associated with pain in laboratory animals has culminated in the development of “grimace scales”. In the context of laboratory animals, these have been developed and evaluated for mice, rats, rabbits, sheep, and ferrets. The prevention or relief of pain in laboratory animals is a fundamental requirement for in vivo research to satisfy community expectations. However, to date it appears that the grimace scales have not seen widespread implementation as clinical pain assessment techniques in biomedical research. In this review, we discuss some of the barriers to implementation of the scales in clinical laboratory animal medicine, progress made in automation of collection, and suggest avenues for future research.

Immunomodulatory properties of mesenchymal stromal cells

Blood ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 3499-3506 ◽  
Author(s):  
Alma J. Nauta ◽  
Willem E. Fibbe
Keyword(s):  
Immune Responses ◽  
Stromal Cells ◽  
Therapeutic Modality ◽  
Future Research ◽  
Clinical Safety ◽  
Clinical Interest ◽  
Immunomodulatory Properties ◽  
Underlying Mechanisms

Abstract Mesenchymal stem cells (MSCs) are multipotential nonhematopoietic progenitor cells capable of differentiating into multiple lineages of the mesenchyme. MSCs have emerged as a promising therapeutic modality for tissue regeneration and repair. Further clinical interest has been raised by the observation that MSCs are immunoprivileged and, more importantly, display immunomodulatory capacities. Although the mechanisms underlying the immunosuppressive effects of MSCs have not been clearly defined, their immunosuppressive properties have already been exploited in the clinical setting. The aim of this review is to critically discuss the immunogenicity and immunomodulatory properties of MSCs, both in vitro and in vivo, the possible underlying mechanisms, the potential clinical use of MSCs as modulators of immune responses in vivo, and to indicate clinical safety concerns and recommendations for future research.

Neurotoxicity of Pesticides: The Roadmap for the Cubic Mode of Action

2020 ◽  
Vol 27 (1) ◽  
pp. 54-77 ◽  
Author(s):  
Bogdan Bumbăcilă ◽  
Mihai V. Putz
Keyword(s):  
Biological Activity ◽  
Wiener Index ◽  
Laboratory Animals ◽  
Covalent Bonds ◽  
Organophosphate Compounds ◽  
Sar Studies ◽  
Structure Activity ◽  
Cubic Structure

Pesticides are used today on a planetary-wide scale. The rising need for substances with this biological activity due to an increasing consumption of agricultural and animal products and to the development of urban areas makes the chemical industry to constantly investigate new molecules or to improve the physicochemical characteristics, increase the biological activities and improve the toxicity profiles of the already known ones. Molecular databases are increasingly accessible for in vitro and in vivo bioavailability studies. In this context, structure-activity studies, by their in silico - in cerebro methods, are used to precede in vitro and in vivo studies in plants and experimental animals because they can indicate trends by statistical methods or biological activity models expressed as mathematical equations or graphical correlations, so a direction of study can be developed or another can be abandoned, saving financial resources, time and laboratory animals. Following this line of research the present paper reviews the Structure-Activity Relationship (SAR) studies and proposes a correlation between a topological connectivity index and the biological activity or toxicity made as a result of a study performed on 11 molecules of organophosphate compounds, randomly chosen, with a basic structure including a Phosphorus atom double bounded to an Oxygen atom or to a Sulfur one and having three other simple covalent bonds with two alkoxy (-methoxy or -ethoxy) groups and to another functional group different from the alkoxy groups. The molecules were packed on a cubic structure consisting of three adjacent cubes, respecting a principle of topological efficiency, that of occupying a minimal space in that cubic structure, a method that was called the Clef Method. The central topological index selected for correlation was the Wiener index, since it was possible this way to discuss different adjacencies between the nodes in the graphs corresponding to the organophosphate compounds molecules packed on the cubic structure; accordingly, "three dimensional" variants of these connectivity indices could be considered and further used for studying the qualitative-quantitative relationships for the specific molecule-enzyme interaction complexes, including correlation between the Wiener weights (nodal specific contributions to the total Wiener index of the molecular graph) and the biochemical reactivity of some of the atoms. Finally, when passing from SAR to Q(uantitative)-SAR studies, especially by the present advanced method of the cubic molecule (Clef Method) and its good assessment of the (neuro)toxicity of the studied molecules and of their inhibitory effect on the target enzyme - acetylcholinesterase, it can be seen that a predictability of the toxicity and activity of different analogue compounds can be ensured, facilitating the in vivo experiments or improving the usage of pesticides.

Metabolism and Distribution of Novel Tumor Targeting Drugs In Vivo

2020 ◽  
Vol 21 (13) ◽  
pp. 996-1008
Author(s):  
Mengli Wang ◽  
Qiuzheng Du ◽  
Lihua Zuo ◽  
Peng Xue ◽  
Chao Lan ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Small Molecule ◽  
High Efficiency ◽  
Tumor Therapy ◽  
Research Progress ◽  
Future Research ◽  
Pharmacokinetic Parameters ◽  
Molecular Characteristics ◽  
Targeted Drugs

Background: As a new tumor therapy, targeted therapy is becoming a hot topic due to its high efficiency and low toxicity. Drug effects of targeted tumor drugs are closely related to pharmacokinetics, so it is important to understand their distribution and metabolism in vivo. Methods: A systematic review of the literature on the metabolism and distribution of targeted drugs over the past 20 years was conducted, and the pharmacokinetic parameters of approved targeted drugs were summarized in combination with the FDA's drug instructions. Targeting drugs are divided into two categories: small molecule inhibitors and monoclonal antibodies. Novel targeting drugs and their mechanisms of action, which have been developed in recent years, are summarized. The distribution and metabolic processes of each drug in the human body are reviewed. Results: In this review, we found that the distribution and metabolism of small molecule kinase inhibitors (TKI) and monoclonal antibodies (mAb) showed different characteristics based on the differences of action mechanism and molecular characteristics. TKI absorbed rapidly (Tmax ≈ 1-4 h) and distributed in large amounts (Vd > 100 L). It was mainly oxidized and reduced by cytochrome P450 CYP3A4. However, due to the large molecular diameter, mAb was distributed to tissues slowly, and the volume of distribution was usually very low (Vd < 10 L). It was mainly hydrolyzed and metabolized into peptides and amino acids by protease hydrolysis. In addition, some of the latest drugs are still in clinical trials, and the in vivo process still needs further study. Conclusion: According to the summary of the research progress of the existing targeting drugs, it is found that they have high specificity, but there are still deficiencies in drug resistance and safety. Therefore, the development of safer and more effective targeted drugs is the future research direction. Meanwhile, this study also provides a theoretical basis for clinical accurate drug delivery.

Prediction of the Omp16 Epitopes for the Development of an Epitope-based Vaccine Against Brucellosis

2019 ◽  
Vol 19 (1) ◽  
pp. 36-45 ◽  
Author(s):  
Marzieh Rezaei ◽  
Mohammad Rabbani-khorasgani ◽  
Sayyed Hamid Zarkesh-Esfahani ◽  
Rahman Emamzadeh ◽  
Hamid Abtahi
Keyword(s):  
Immune Responses ◽  
B Cell ◽  
Dairy Products ◽  
Bioinformatics Analysis ◽  
Epitope Prediction ◽  
Animal Husbandry ◽  
Zoonotic Diseases ◽  
Recombinant Vaccines ◽  
Protective Capacity ◽  
Tertiary Structures

Background:Brucellosis is an infectious disease caused by Brucella bacteria that cause disease in animals and humans. Brucellosis is one of the most common zoonotic diseases transmitted from animals-to-human through direct contact with infected animals and also consumption of unpasteurized dairy products. Due to the wide incidence of brucellosis in Iran and economical costs in industrial animal husbandry, Vaccination is the best way to prevent this disease. All of the available commercial vaccines against brucellosis are derived from live attenuated strains of Brucella but because of the disadvantage of live attenuated vaccines, protective subunit vaccine against Brucella may be a good candidate for the production of new recombinant vaccines based on Brucella Outer Membrane Protein (OMP) antigens. In the present study, comprehensive bioinformatics analysis has been conducted on prediction software to predict T and B cell epitopes, the secondary and tertiary structures and antigenicity of Omp16 antigen and the validation of used software confirmed by experimental results.Conclusion:The final epitope prediction results have proposed that the three epitopes were predicted for the Omp16 protein with antigenicity ability. We hypothesized that these epitopes likely have the protective capacity to stimulate both the B-cell and T-cell mediated immune responses and so may be effective as an immunogenic candidate for the development of an epitope-based vaccine against brucellosis.

scholarly journals Lysosomotropic agents including azithromycin, chloroquine and hydroxychloroquine activate the integrated stress response

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ai-Ling Tian ◽  
Qi Wu ◽  
Peng Liu ◽  
Liwei Zhao ◽  
Isabelle Martins ◽  
...  
Keyword(s):  
Stress Response ◽  
Immune Responses ◽  
Initiation Factor ◽  
Integrated Stress Response ◽  
Serine Residue ◽  
Eif2α Phosphorylation ◽  
Lysosomotropic Agents ◽  
Cultured Human Cells

AbstractThe integrated stress response manifests with the phosphorylation of eukaryotic initiation factor 2α (eIF2α) on serine residue 51 and plays a major role in the adaptation of cells to endoplasmic reticulum stress in the initiation of autophagy and in the ignition of immune responses. Here, we report that lysosomotropic agents, including azithromycin, chloroquine, and hydroxychloroquine, can trigger eIF2α phosphorylation in vitro (in cultured human cells) and, as validated for hydroxychloroquine, in vivo (in mice). Cells bearing a non-phosphorylatable eIF2α mutant (S51A) failed to accumulate autophagic puncta in response to azithromycin, chloroquine, and hydroxychloroquine. Conversely, two inhibitors of eIF2α dephosphorylation, nelfinavir and salubrinal, enhanced the induction of such autophagic puncta. Altogether, these results point to the unexpected capacity of azithromycin, chloroquine, and hydroxychloroquine to elicit the integrated stress response.

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