Tick-borne Diseases, Transmission, Host Immune Responses, Diagnosis and Control

Present review article explains tick-borne diseases, transmission, host immune responses, diagnosis and control in relation to climatic variations. Ticks are hematophagous ectoparasites which suck large volumes of blood from livestock and humans. They release large numbers of protozoans, bacteria, rickettsia and viral pathogens during blood feeding and transmit disease pathogens through saliva. Due to heavy blood sucking by ticks animals face significant blood and weight loss that affect their overall health. Due to more severe illness, high economic losses were noted in livestock. This article highlights medically important tick borne diseases in man and livestock, its pathogenesis, diagnosis and treatment methods. The present article emphasizes invasion of hosts, host-pathogen interactions, tick saliva toxin induced host immune responses and biological effects. This article highlighted various tick control methods i.e. physical killing, acaricidal, biological, hormonal, genetic and immunological methods such as administration of protective antibody and vaccines for disease control in human being and his livestock. The authors suggest non-chemical environmentally safe methods for successful control of tick borne diseases to kill cattle, bird and canine invading ticks.

Comprehensive Analysis of the Potential Immune-Related Biomarker Transporter Associated With Antigen Processing 1 That Inhibits Metastasis and Invasion of Ovarian Cancer Cells

Transporter associated with antigen processing 1 (TAP1) is a protein related immune regulation and plays a role in several malignant tumors. However, the effect of TAP1 on immune infiltration, immunotherapy, and metastasis in different cancers has not been reported till date. The cancer genome atlas database, the tumor immune estimation resource database, and the estimation of stromal and immune cells in malignant tumors using expression (ESTIMATE) algorithm were used to determine the correlation between TAP1 expression and the prognosis of a variety of cancers, immune infiltration, immune checkpoint genes, DNA methylation, and neoantigens. Various enrichment analyses were used to study the correlation between TAP1 and key transcription factors using the Kyoto encyclopedia of genes and genomes (KEGG) pathway in ovarian cancer. Immunological methods were used to evaluate the expression of TAP1 protein in ovarian and cervical cancer, and Kaplan–Meier analysis was used to analyze the prognostic value of TAP1. RNA interference (RNAi) was used to verify the effect of TAP1 on ovarian cancer. Compared with normal tissues, cancer tissues showed a significant increase in the expression of TAP1, and TAP1 expression was related to the poor prognosis of cancers such as ovarian cancer. The expression level of TAP1 was correlated with immune checkpoint genes, DNA methylation, tumor mutation burden, microsatellite instability, and neoantigens in various cancers. Our results showed that TAP1 was upregulated in ovarian cancer cell lines and was associated with poor prognosis. Further, we verified the expression of TAP1-related transcription factors (MEF2A and LEF1) and found that TAP1 was closely related to ovarian cancer metastasis in vitro and in vivo. These results indicated that TAP1 could be used as a biomarker for the diagnosis and prognosis of cancer and as a new therapeutic target.

Intake of Flavonoids from Astragalus Membranaceus Ameliorated Brain Impairment in Diabetic Mice Via Modulating Brain-Gut Axis

Background: Brain impairment is one of a major complication of diabetes. Dietary flavonoids have been recommended to prevent brain damage. Astragalus membranaceus is a herbal medicine commonly used to relieve the complications of diabetes. Flavonoids is one of the major ingredients of Astragalus membranaceus, but its function and mechanism on diabetic encepholopathy is still unknown.Methods: Type 2 diabetes mellitus (T2DM) model was induced by high fat diet and STZ in C57BL/6J mice, and BEnd.3 and HT22 cell lines were applied in the in vitro study. Quality of flavonoids was evaluated by LC-MS/MS. Differential expressed proteins in the hippocampus were evaluated by proteomics; influence of the flavonoids on composition of gut microbiota was analyzed by metagenomics. Mechanism of the flavonoids on diabetic encepholopathy was analyzed by Q-PCR, Western Blot, and multi-immunological methods et al. Results: We found that flavonoids from Astragalus membranaceus (TFA) significantly ameliorated brain damage by modulating gut-microbiota-brain axis: TFA oral administration decreased fasting blood glucose and food intake, repaired blood brain barrier, protected hippocampus synaptic function; improved hippocampus mitochondrial biosynthesis and energy metabolism; and enriched the intestinal microbiome in high fat diet/STZ-induced diabetic mice. In the in vitro study, we found TFA increased viability of HT22 cells and preserved gut barrier integrity in CaCO2 monocellular layer, and PGC1α/AMPK pathway participated in this process. Conclusion: Our findings demonstrated that flavonoids from Astragalus Membranaceus ameliorated brain impairment via gut-brain axis. Our present study provided an alternative solution on preventing and treating diabetic cognition impairment.

Evaluation of different platforms for the detection of anti-SARS coronavirus-2 antibodies, Thailand

Background Antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) help determine previous infection in individuals, regardless of whether they are asymptomatic or symptomatic. The detection of antibodies serves several purposes, including supporting other assays for disease diagnosis, conducting seroepidemiological studies, and evaluating vaccines. Many platforms of immunological methods for anti-SARS-CoV-2 antibody detection and their performance require validation. Methods This study evaluated the test performance of three autoanalyzer-based assays (Architect IgG, Vitros IgG, and Vitros total Ig) and one manual ELISA (Wantai total Ig) against a microneutralization (microNT) assay on the detection of SARS-CoV-2 antibodies. Furthermore, an indirect immunofluorescence assay verified the discordant results between the microNT and commercial assays. The test sensitivity, specificity, positive predictive value, and negative predictive value were determined based on four groups of 1005 serum samples: 102 COVID-19 prepandemic sera, 45 anti-SARS-CoV-2 positive sera, 366 sera of people at risk, and 492 sera of citizens returning from countries with a high prevalence of infection. Results The analyses as a whole showed that the performance of these commercial assays was comparable. Each group was also analysed separately to gain further insight into test performance. The Architect did not detect two positive sera of people at risk (prevalence of infection 0.55%). The other methods correctly identified these two positive sera but yielded varying false-positive results. The group of returning travellers with an infection rate of 28.3% (139 of 492) better differentiated the test performance of individual assays. Conclusions High-throughput Architect and Vitros autoanalyzers appear appropriate for working on large sample sizes in countries that can afford the cost. The Wantai ELISA, while requiring more individual time and technical skill, may provide reliable results at a lower cost. The selection of assays will depend on the laboratory facilities and feasibility.

Pathogenetic justification of the use of criteria for determining the lifespan and age of wound caused by mechanical damage

The aim of the study is detailed analysis of the literature on the existing methods for determining the lifetime and inflicting of mechanical damage. It was found that the existing methods have very large discrepancies in assessing the infliction of damage. The use of the same research methods by different researchers has lead to results that may differ. This can lead to obtaining insufficiently substantiated or even erroneous conclusions about the infliction of mechanical damage. The authors explain this by the fact that the body reacts to damage by the development of a typical pathological process – inflammation. Forensic methods that exist for determining the age of wound are aimed at obtaining an expert assessment of individual manifestations of the pathogenesis of inflammation by morphological, biochemical and immunological methods. Determination of the age of wound is actually the determination of a specific stage in the pathogenesis of inflammation, which is observed at the time of the examination and the timing of the development, which is known from the literature. Taking into account the stages of the pathogenesis of inflammation as a typical pathological process, in the area of tissue damage makes it possible to more accurately determine the duration of the infliction of mechanical damage. The individual reactivity of the organism, which determines the features of the course of any typical pathological process, will determine the individual timing of the development of certain morphological, biochemical and immunological changes in the area of damage.

Prevalence of Bovine Viral Diarrhea Virus in Ovine and Caprine Flocks: A Global Systematic Review and Meta-Analysis

Background: Bovine viral diarrhea virus (BVDV) is the causative agent of bovine viral diarrhea. It can infect cattle, sheep, pigs, and other animals, causing diarrhea, miscarriage, and stillbirth, among other symptoms, and it can result in huge economic losses to animal husbandry. There are reports on BVDV infection rates in sheep and goat herds from all over the world and this meta-analysis aimed to evaluate the prevalence of and risk factors for BVDV in sheep and goats.Results: Using the data of 41,297 sheep and goats in 24 countries/regions to calculate a comprehensive prevalence rate for BVDV. The overall prevalence of BVDV infection in sheep and goats was estimated to be 8.6% (95% CI: 5.2–12.7) by immunological methods and 7.3% (95% CI: 2.7–13.7) by molecular methods. Analysis by national income level revealed that prevalence is higher in middle-income countries than in high-income countries (P < 0.05). The study also compared prevalence rates by species of BVDV, sampling year, and test species, but did not find significant differences.Conclusion: This systematic review and meta-analysis is the first to determine the global prevalence of BVDV in ovine and caprine flocks. The prevalence of BVDV in sheep and goat populations varies from region to region, and the situation is not optimistic in some countries.

Molecular serological characteristics of ABO system A antigen

Background. One of the polymorphic antigens in the ABO system is antigen A, which includes many allelic variants with different expression. Immunological methods for determining the blood group of the ABO system have limitations in their use, including due to the presence of weekly expressed antigens in humans. For the correct determination of blood group according to the ABO system, genetic typing is becoming increasingly important. 89 alleles of the ABO*A gene are known. Knowledge of ABO*A gene polymorphisms and their prevalence contributes to the prevention of errors in determining the blood group of donors and recipients.Objective: to describe variants of ABO*A gene alleles in Russians and serological characteristics of the antigens encoded by them.Materials and methods. The blood of 14,000 people was examined. The blood group was determined using anti-A, anti- Aweak, anti-B, lectin (anti-A1) and gel cards. A molecular study of ABO*A gene polymorphisms was conducted in 151 people. Polymerase chain reaction with sequence-specific primers and direct Sanger sequencing were used.Results. 7 different ABO*A alleles were detected, including the ABO*A1.01 and ABO*A1.02 alleles. In 118 individuals with a weak A antigen, the ABO*A2.01 allele was the most frequent (87.29 %). Rare alleles ABO*A2.06 (5.93 %), ABO*AW.06 (4.23 %), ABO*A2.09 (0.85 %) and ABO*Ax (1.70 %) were found. Serological characteristics of A antigens variants depending on genotypes are described, variants A1, A2, A3 and very weak A were detected. Extraagglutinins α1 were absent in all persons with weakened A antigen.Conclusion. Small or mixed agglutination with Coliclones or red blood cell stratification in the gel suggest the presence of antigen A with weakened expression. Modern molecular methods make it possible to identify rare gene alleles and genotypes. Erythrocyte genomics helps to resolve the ambiguity of the serological results allows understanding the true mechanisms of particular phenotype formation and makes a contribution to ensuring the immunological safety of blood components transfusions.

Immunological Analytical Techniques for Cosmetics Quality Control and Process Monitoring

Cosmetics analysis represents a rapidly expanding field of analytical chemistry as new cosmetic formulations are increasingly in demand on the market and the ingredients required for their production are constantly evolving. Each country applies strict legislation regarding substances in the final product that must be prohibited or regulated. To verify the compliance of cosmetics with current regulations, official analytical methods are available to reveal and quantitatively determine the analytes of interest. However, since ingredients, and the lists of regulated/prohibited substances, rapidly change, dedicated analytical methods must be developed ad hoc to fulfill the new requirements. Research focuses on finding innovative techniques that allow a rapid, inexpensive, and sensitive detection of the target analytes in cosmetics. Among the different methods proposed, immunological techniques are gaining interest, as they make it possible to carry out low-cost analyses on raw materials and finished products in a relatively short time. Indeed, immunoassays are based on the specific and selective antibody/antigen reaction, and they have been extensively applied for clinical diagnostic, alimentary quality control and environmental security purposes, and even for routine analysis. Since the complexity and variability of the matrices, as well as the great variety of compounds present in cosmetics, are analogous with those from food sources, immunological methods could also be applied successfully in this field. Indeed, this would provide a valid approach for the monitoring of industrial production chains even in developing countries, which are currently the greatest producers of cosmetics and the major exporters of raw materials. This review aims to highlight the immunological techniques proposed for cosmetics analysis, focusing on the detection of prohibited/regulated compounds, bacteria and toxins, and allergenic substances, and the identification of counterfeits.

959 Safety and anti-tumor activity of TCR-engineered autologous, PRAME-directed T cells across multiple advanced solid cancers at low doses – clinical update on the ACTengine® IMA203 trial

BackgroundAdoptive cell therapy demonstrated significant clinical benefit in patients with hematological malignancies but results in most solid tumors have been less encouraging so far.In the IMA203 trial we are treating advanced solid cancer patients utilizing TCR-engineered T cells (TCR-T) directed against an HLA-A*02-restricted peptide derived from the highly prevalent cancer testis antigen PRAME. This target was selected due to homogenous expression and exceptionally high target peptide density per tumor cell (assessed by quantitative mass spectrometry), two features we hypothesize to be critical determinants of anti-tumor activity in TCR-T trials.MethodsThis ongoing first-in-human, dose escalation, multi-indication trial enrolls HLA-A*02:01- and PRAME-positive recurrent and/or refractory solid cancer patients, who failed all available standard treatments. Eligible patients undergo leukapheresis and an autologous TCR-T product is manufactured. After lymphodepletion with fludarabine and cyclophosphamide, T cells are infused, followed by low-dose IL-2. The primary objective of the trial is to assess the safety and tolerability of IMA203. Secondary objectives are to evaluate the anti-tumor activity and pharmacodynamics using molecular and immunological methods.ResultsAs of August 15, 2021, 16 heavily pre-treated patients received IMA203 T cells across multiple escalating dose levels (DL). Absolute IMA203 doses infused ranged from 0.08 to 0.81x109 transduced CD8 T cells per patient, which to our knowledge did not lead to anti-tumor responses in other TCR-T trials. Treatment-emergent adverse events after IMA203 infusion were transient and manageable. Most common events were expected cytopenias (G1-4), CRS and ICANS (both G1-2) and 1 DLT in DL2 (reported earlier). All evaluable patients (N=12) achieved disease control (i.e. best overall response: stable disease [SD] or partial response [PR]) and 6 patients demonstrated PRs according to RECIST1.1 with 2 of these PRs being confirmed. While all 3 patients treated at DL1 (median dose: 0.11x109) experienced SD, a PR was observed in 6/9 patients treated beyond DL1 (median dose: 0.30x109). Responses were seen in patients with synovial sarcoma (N=3), malignant melanoma (N=2) and head and neck cancer (N=1). Robust engraftment of T cells was observed in all patients and tumor infiltration by TCR-modified T cells was demonstrated in patients with evaluable on-treatment biopsies.ConclusionsTo our knowledge IMA203 is the first TCR-T product candidate that induced frequent tumor responses across multiple solid cancers using transduced T cells at doses below 1 billion and has a manageable safety profile. The next step is to assess response rates at higher dose levels and durability of responses.Trial RegistrationNCT03686124Ethics ApprovalThe study was approved by the institutional review board/ethics committee as required for each participating site.

The Toxicity Testing of Cyanobacterial Toxins In Vivo and In Vitro by Mouse Bioassay: A Review

: Different biological methods based on bioactivity are available to detect cyanotoxins, including neurotoxicity, immunological interactions, hepatotoxicity, cytotoxicity, and enzymatic activity. The mouse bioassay is the first test employed in laboratory cultures, cell extracts, and water bloom materials to detect toxins. It is also used as a traditional method to estimate the LD50. Concerning the ease of access and low cost, it is the most common method for this purpose. In this method, a sample is injected intraperitoneally into adult mice, and accordingly, they are assayed and monitored for about 24 hours for toxic symptoms. The toxin can be detected using this method from minutes to a few hours; its type, e.g., hepatotoxin, neurotoxin, etc., can also be determined. However, this method is nonspecific, fails to detect low amounts, and cannot distinguish between homologues. Although the mouse bioassay is gradually replaced with new chemical and immunological methods, it is still the main technique to detect the bioactivity and efficacy of cyanotoxins using LD50 determined based on the survival time of animals exposed to the toxin. In addition, some countries oppose animal use in toxicity studies. However, high cost, ethical considerations, low-sensitivity, non-specificity, and prolonged processes persuade researchers to employ chemical and functional analysis techniques. The qualitative and quantitative analyses, as well as high specificity and sensitivity, are among the advantages of cytotoxicity tests to investigate cyanotoxins. The present study aimed at reviewing the results obtained from in-vitro and in-vivo investigations of the mouse bioassay to detect cyanotoxins, including microcystins, cylindrospermopsin, saxitoxins, etc.