Efficacy evaluation of anti-DEC-IgY against antibiotic-resistant diarrhoeagenic Escherichia coli.

Introduction. The rise of multi-drug-resistant bacteria poses a global threat. In 2017, the World Health Organization identified 12 antibiotic-resistant 'priority pathogens', including Enterobacteriaceae, highlighting the menace of Gram-negative bacteria. Diarrhoeagenic Escherichia coli (DEC)-induced diarrhoea is particularly problematic for travellers and infants. In contrast to other antibiotic alternatives, passive immunotherapy is showing promise by providing immediate and precise protection. However, mammalian-sourced antibodies are costly, hindering large-scale production. Egg-laying chicken-derived IgY antibodies present a cost-effective, high-yield solution, revolutionizing antibody-based therapeutics compared to mammalian IgG.Hypothesis/Gap Statement. This study hypothesized that developing anti-DEC-IgY could combat DEC infections effectively.Aim. The primary aim was to develop anti-DEC-IgY and assess its potential in DEC-induced diarrhoeal management.Method. Chickens were immunized with DEC antigens to induce an immune response. IgY antibodies were extracted from immune eggs and purified using ion-exchange column chromatography. Anti-DEC-IgY's ability to inhibit DEC growth was evaluated through growth inhibition assays. Anti-DEC-IgY's capacity to prevent E. coli adhesion was assessed using mice intestinal mucosa. In vivo experiments measured pathogen colonization reduction and infection severity reduction. P values were calculated to confirm statistical significance.Result. The antibacterial efficacy of anti-DEC-IgY by growth inhibition assay demonstrated that 25 mg ml-1 of IgY could inhibit the DEC growth. The anti-adherence-property was tested using mice intestinal mucosa and found that anti-DEC-IgY could prevent the E. coli adhesion. In vivo results suggest that 12 mg ml-1 of IgY will reduce the pathogen colonization in intestine and reduce the severity of the infection. The P values between the experimental groups confirm the statistical significance of the findings.Conclusion. The study findings suggest that IgY-based passive immunotherapy could be a potential strategy for managing the risks associated with antibiotic-resistant bacterial infections. Additionally, this study paves the way for the development of IgY-related research and applications in India.

The concept of Big Four: Road map from snakebite epidemiology to antivenom efficacy.

Snake envenomation is a life-threatening disease caused by the injection of venom toxins from the venomous snake bite. Snakebite is often defined as the occupational or domestic hazard mostly affecting the rural population. India experiences a high number of envenoming cases and fatality due to the nation's diversity in inhabiting venomous snakes. The Indian Big Four snakes namely Russell's viper (Daboia russelii), spectacled cobra (Naja naja), common krait (Bungarus caeruleus), and saw-scaled viper (Echis carinatus) are responsible for majority of the snake envenoming cases and death. The demographic characteristics including occupation, stringent snake habitat management, poor healthcare facilities and ignorance of the rural victims are the primary influencers of high mortality. Biogeographic venom variation greatly influences the clinical pathologies of snake envenomation. The current antivenoms against the Big Four snakes are found to be less immunogenic against the venom toxins emphasizing the necessity of alternative approaches for antivenom generation. This review summarizes the burden of snake envenomation in India by the Big Four snakes including the geographic distribution of snake species and biogeographic venom variation. We have provided comprehensive information on snake venom proteomics that has aided the better understanding of venom induced pathological features, summarized the impact of current polyvalent antivenom therapy highlighting the need for potential antivenom treatment for the effective management of snakebites.

Role of tau protein in Alzheimer's disease: The prime pathological player.

Alzheimer's disease (AD) is a prevalently found tauopathy characterized by memory loss and cognitive insufficiency. AD is an age-related neurodegenerative disease with two major hallmarks which includes extracellular amyloid plaques made of amyloid-ß (Aß) and intracellular neurofibrillary tangles of hyperphosphorylated tau. With population aging worldwide, there is an indispensable need for treatment strategies that can potentially manage this developing dementia. Despite broad researches on targeting Aß in the past two decades, research findings on Aß targeted therapeutics failed to prove efficacy in the treatment of AD. Tau protein with its extensive pathological role in several neurodegenerative diseases can be considered as a promising target candidate for developing therapeutic interventions. The abnormal hyperphosphorylation of tau plays detrimental pathological functions which ultimately lead to neurodegeneration. This review will divulge the importance of tau in AD pathogenesis, the interplay of Aß and tau, the pathological functions of tau, and potential therapeutic strategies for an effective management of neuronal disorders.

Inflammation in myocardial injury- Stem cells as potential immunomodulators for myocardial regeneration and restoration.

The ineffective immunosuppressant's and targeted strategies to neutralize inflammatory mediators have worsened the scenario of heart failure and have opened many questions for debate. Stem cell therapy has proven to be a promising approach for treating heart following myocardial infarction (MI). Adult stem cells, induced pluripotent stem cells and embryonic stem cells are possible cell types and have successfully shown to regenerate damaged myocardial tissue in pre-clinical and clinical studies. Current implications of using mesenchymal stem cells (MSCs) owing to their immunomodulatory functions and paracrine effects could serve as an effective alternative treatment option for rejuvenating the heart post MI. The major setback associated with the use of MSCs is reduced cell retention, engraftment and decreased effectiveness. With a few reports on understanding the role of inflammation and its dual effects on the structure and function of heart, this review focuses on these missing insights and further exemplifies the role of MSCs as an alternative therapy in treating the pathological consequences in myocardial infarction (MI).

Chicken egg yolk antibody (IgY) as diagnostics and therapeutics in parasitic infections - A review.

Early diagnosis and treatment of parasitic diseases are indispensable to combat parasites mediated morbidity and mortality in humans and animals. Mammalian sourced antibodies are being successfully used in immunotherapy and immunoassays. However, their increased conservation amongst mammals, involves them in unnecessary interaction and immune mediated pathologies, obstructing their applications in certain approaches in immunoassays. Further, the high production cost and difficulty to achieve high and stable antibody titer hampers their utility for therapeutic purposes. In recent years, chicken egg yolk immunoglobulin, termed as immunoglobulin Y (IgY) has attracted noticeable consideration since it poses greater advantages than mammalian IgG including high yield, low cost and convenience. IgY has unique properties which are being exploited in different aspects for its applications in research, diagnosis and therapy. This review gives an overview of the research outcomes pertaining to chicken IgY as diagnostics and therapeutics in parasitology.

Immunoglobulin Transporting Receptors Are Potential Targets for the Immunity Enhancement and Generation of Mammary Gland Bioreactor.

The functions of immunoglobulin transporting receptors (Ig transporting receptors) in immune system encompass from passive immunity to adaptive immunity by transporting immunoglobulins (Igs) and prolonging their half-life as well as enhancing immunosurveillance. Prior to the weaning, Ig transportations from mother to offspring confer the immediate passive immunity for neonates. After the weaning, FcRn and polymeric immunoglobulin receptor on infant intestinal epithelial cells retrieve Ig in intestinal lamina propria into the gut lumen for preventing pathogen invasion. This is not only improving the pathological consequences of infection but also helping the neonates for developing their own immune response; besides it would be the guidance for designing novel vaccines. Moreover, the investigations on Ig transporting receptors over-expressed transgenic animals have been carried out to improve Ig concentrations in serum and milk; thus, it would be a sustainable method to produce antibody-enriched milk-derived colostrum replacer for neonates. In order to generate mammary gland bioreactor, a series of methods have been developed for enhanced regulation of Ig transporting receptors expression and Ig transportation.

A comparative evaluation of six principal IgY antibody extraction methods.

Egg yolk has been considered a promising source of antibodies. Our study was designed to compare six principal IgY extraction methods (water dilution, polyethylene glycol [PEG] precipitation, caprylic acid extraction, chloroform extraction, phenol extraction, and carrageenan extraction), and to assess their relative extraction efficiencies and the purity of the resulting antibodies. The results showed that the organic solvents (chloroform or phenol) minimised the lipid ratio in the egg yolk. The water dilution, PEG precipitation and caprylic acid extraction methods resulted in high yields, and antibodies purified with PEG and carrageenan exhibited high purity. Our results indicate that phenol extraction would be more suitable for preparing high concentrations of IgY for non-therapeutic usage, while the water dilution and carrageenan extraction methods would be more appropriate for use in the preparation of IgY for oral administration.

Development of indirect competitive ELISA using egg yolk-derived immunoglobulin (IgY) for the detection of Gentamicin residues.

Gentamicin (Gent) is an aminoglycoside antibiotic being used in livestock sector. Gent residues could cause some genetic disorders by nonsense mutations. This study aimed to develop IgY-based ELISA for the detection of Gent in animal products. Gent was conjugated with Bovine serum albumin (BSA) by carbodiimide method for further immunization in the laying chickens. PEG-6000 extraction method was employed to extract IgY from the egg yolk. The titer of anti-Gent-IgY attained the peak of 1:256,000 after the 5(th) booster immunization. Checkerboard titration confirmed that, anti-Gent IgY in 1:2,000 dilution could give an Optical Density (OD) 1.0 at 2 µg mL(-1) of Gent-OVA coating concentration. IgY-based indirect competitive ELISA (Ic-ELISA) showed that, the IC50 value of anti-Gent IgY was 2.69 ng mL(-1) and regression curve equation was y = -16.27x + 56.97 (R(2) = 0.95, n = 3), confirming that, the detection limit (LOD, IC10 value) was 0.01 ng mL(-1). Recoveries from fresh milk, pork and chicken samples were ranged from 69.82% to 94.32%, with relative standard deviation lower than 10.88%. Our results suggested that generated anti-Gent IgY antibodies can be used in routine screening analysis of Gent residues in food samples.

Chronobiological studies of chicken IgY: monitoring of infradian, circadian and ultradian rhythms of IgY in blood and yolk of chickens.

IgY is the functional equivalent of mammalian IgG found in birds, reptiles and amphibians. Many of its biological aspects have been explored with different approaches. In order to evaluate the rhythmicity of serum and yolk IgY, four chickens were examined and reared under the same conditions. To monitor biological oscillations of IgY in yolk and serum, the eggs and blood samples were collected over a 60 day period and the rhythm of yolk and serum IgY was determined by direct-ELISA. Results indicated that, there is a significant circaseptan rhythm in yolk IgY and circaquattran rhythm in serum IgY. The serum IgY concentration reached a peak in the morning, decreased to a minimum during the daytime and increased again at night revealing a significant circadian rhythm was superimposed by an ultradian rhythm. These data are suited to address the controversies concerning the IgY concentration in egg yolk and blood of laying hens. In addition, this study raised new questions, if the different rhythms in yolk and serum are concerned.

Neonatal Fc receptor (FcRn): a novel target for therapeutic antibodies and antibody engineering.

The biomedical applications of antibodies as prophylactics, therapeutics and diagnostics are developing rapidly. Neonatal Fc receptor (FcRn) is a major IgG Fc receptor capable of facilitating the translocation of IgG. FcRn can protect IgG from intracellular catabolism, thereby increasing its half-life. In recent decade, the interaction between FcRn and the Fc region has been reported with the focuses on either prolonging the plasma half-life of therapeutic IgG or shortening the half-life of pathogenic IgG. The FcRn-IgG interaction can be altered by modifying the Fc region to change their affinity (increase or decrease), and/or by reducing the Fc fragments of IgG to enhance its penetration into tissues or cells. By over expression of FcRn, the exogenous catabolism can be reduced, meanwhile the circulating IgG level could be enhanced. It has been confirmed in different FcRn over-expressed transgenic mice models, substantial humoral responses against antigens with weak immunogenicity can be mounted. In addition, designing inhibitors for FcRn-IgG interaction is another application prospect for treating IgG-mediated autoimmune diseases. Recent research advancements strengthen the understanding that FcRn is a key and promising drugable target in IgG intervention in the field of antibody engineering.