Indian Veterinary Research Institute

Demyelination leads to neuropathies and clinical deficits. Chemical remyelinating agents have variable efficacy and severe undesirable effects. Withania somnifera and Ginkgo biloba are traditionally known for possessing neuroprotective effects. The present study endeavors to reverse the demyelination using Withania somnifera root extract (WNLP) and Ginkgo biloba leaf extract (GNLP) liposomes prepared using thin-film hydration. The mean particle size (89.7nm for WNLP, 85.5nm for GNLP), zeta potential (−0.21mV for WNLP, +0.455mV for GNLP), and encapsulation efficiency (98.7% for WNLP, 97.5% for GNLP) were recorded. FTIR analysis indicated similar absorption peaks between the crude extracts and nano-liposomal formulations, with slight shifts observed. Scanning electron microscopy confirmed smooth, spherical structures. To evaluate the therapeutic efficacy of oral gavage of WNLP and GNLP in a cuprizone-induced demyelinated mice model, they were randomly divided into groups, namely Control (Healthy, Sham and Vehicle), WNLP (low and high dose), GNLP (low and high dose), Ginkgo biloba crude extract (low and high dose) and Prednisolone. Treatment efficacy was assessed using behavioral tests (SHIRPA, Rota-rod, Hot-plate, NORT, and EPM), hematobiochemical, histology, and immunohistochemical analyses. The GNLP in high doses had significant improvement compared to others, highlighting its potential as a promising therapy for demyelinating neuropathies, paving the way for advancements in neurobiomedical science.

Salmonella Typhimurium is one of the leading causes of foodborne illness in humans. Poultry products are the main source of infection for humans. Here we report the whole-genome sequences of Salmonella Typhimurium strain E-5591 (a field poultry isolate) and its mutant strains lacking the various methionine sulfoxide reductase genes.

Goats are vital to the rural economy of India, contributing significantly to livelihoods, nutrition, and agricultural sustainability. With a population of 148.88 million, India holds the world’s largest goat population, comprising 41 recognized indigenous breeds. These goats provide milk, meat, and fiber, particularly in marginal environments. The genomic advancements in goat research have revolutionized the understanding of genetic diversity, adaptation, and trait improvement. Whole-genome sequencing (WGS), single nucleotide polymorphism (SNP) arrays and transcriptomics have unveiled genetic markers associated with production, disease resistance, and reproductive traits. Genomic tools such as the Illumina Goat SNP50K BeadChip and high-throughput sequencing technologies have facilitated the identification of selection signatures and quantitative trait loci (QTL), influencing economically important traits like milk yield, meat quality, and prolificacy. Notably, genes such as DGAT1, GHR, BMPR1B, and HSP70 have been linked to production efficiency, reproductive performance, and climate resilience. Genome-wide association studies (GWAS) and genomic selection (GS) have enabled precision breeding, enhancing genetic gains and reducing inbreeding risks. The application of RNA sequencing has provided insights into gene expression patterns governing lactation, growth, and reproductive efficiency. Epigenomic studies, focusing on DNA methylation and histone modifications, have highlighted regulatory mechanisms underpinning prolificacy and muscle development. Conservation genomics has played a pivotal role in safeguarding native breeds by assessing genetic diversity and mitigating inbreeding depression. Indicine goat breeds, such as Jamunapari, Beetal, Barbari, and Black Bengal, exhibit unique genetic adaptations to diverse agro-climatic conditions, emphasizing the need for their conservation. Emerging technologies, including CRISPR-Cas9 gene editing, hold promise for precision breeding to enhance productivity and disease resistance. Integrating genomics with artificial intelligence (AI) and big data analytics is poised to revolutionize goat breeding and management. Future efforts should focus on expanding genomic databases, developing breed-specific reference genomes, and promoting genomic literacy among farmers to ensure sustainable goat production and improve rural livelihoods in India.

Antimicrobial peptides (AMPs) are essential components of the innate immune system in living organisms. They not only have significant impacts on inhibiting microbial growth, but show multiple properties while exhibiting therapeutic potentials. Over the past years, a wide diversity of AMPs has been identified from different natural sources like plants, animals and microorganisms. Recently mesenchymal stem cells (MSCs) have been shown to exhibit strong antimicrobial effects both in vitro as well as in vivo possibly by expressing different families of AMPs depending upon source of cells. It has been revealed that species variations as well as tissue specific localization are responsible for the variation in expressions of AMPs families. In recent years new synthetic peptides are given importance in biomedical sciences. Herein we aim to review the current state of knowledge on identification of AMPs from various types of adult stem cells and tissues in animals including species variations in cell sources and culture conditions. Further, a glimpse of chemical nature and mode of actions of AMPs in general have also been described. In the last part we have also tried to summarize the opportunities and challenges to the development of these peptides in clinical trials for prospective applications.

Despite significant progress in cartilage regeneration therapeutics, several challenges remain in achieving optimal results under in vivo conditions. The present research evaluated the chondrogenic potential of poly(glycerol sebacate) copolymer nanofibrous scaffold (PGS NF) loaded with growth differentiation factor-5 incorporated sugar glass nanoparticles (SGnP-GDF5), in combination with allogenic bone marrow-derived mesenchymal stem cells (BM-MSC) in a rabbit model. A full-thickness chondral defect of 4 mm diameter was created in the trochlear facet of the left femur of rabbits using a Brad point drill bit. PGS NF was used in group B, BM-MSC laden PGS NF in group C, SGnP-GDF5 loaded PGS NF in group D, and BM-MSC laden SGnP-GDF5 loaded PGS NF in group E. Five animals from each group were sacrificed on days 60 and 90 post-treatment. The samples were assessed based on gross morphology, histopathology, scanning electron microscopy (SEM), and micro-computed tomography (micro-CT) analysis to evaluate regeneration. The SGnP-GDF5 PGS NF group and the BM-MSC laden SGnP-GDF5 PGS NF group exhibited superior cartilage regeneration, closely resembling hyaline cartilage. Histopathological evaluation revealed a columnar pattern of chondrocytes, along with an optimal concentration of proteoglycans and collagen in the extracellular matrix of the newly formed cartilage, indicating robust regeneration in both groups. Furthermore, the SEM and micro-CT analysis findings highlighted the exceptional quality of the repaired tissue in these groups. The release of GDF5 from SGnP and the expedient microenvironment provided by the NF scaffold augmented chondrogenic differentiation, resulting in superior cartilage tissue regeneration. Graphical Abstract

Nanoparticles are emerging as a potential substitute for antibiotics for combating bacterial infections and addressing the challenge of antimicrobial resistance (AMR). This research evaluates the in vitro and in vivo efficacy of zinc oxide (ZnO)-copper oxide (CuO) nanoparticles (NPs) against Escherichia coli infection in poultry. In vitro antibacterial activity of ZnO-CuO NPs at three concentrates (25 + 10 µg/ml, 37.5 + 15 µg/ml, 50 + 20 µg/ml) was compared with routinely used antibiotics (colistin, doxycycline, tetracycline, and streptomycin) in poultry by disc diffusion assay. Further, broth microdilution assay was performed using the ZnO and CuO NPs. For the in vivo study, 12-day-old cobb broiler chicks were segregated into control negative, control positive, colistin treated, and ZnO-CuO-NP at dose rates of 25 + 10 mg/kg, 37.5 + 15 mg/kg, and 50 + 20 mg/kg. All birds excluding negative control were intramuscularly infected with 0.2 ml E. coli (10⁷ CFU/ml). After E. coli inoculation, treatments were administered orally for 6 days and birds were slaughtered on the 7th and 11th days post-infection. The results of antimicrobial sensitivity testing showed that the lower concentrate of ZnO-CuO NPs exhibited similar antibacterial activity as Colistin-25 µg. This antibiotic was selected in the experimental trial as it showed a greater zone of inhibition. The minimum inhibitory concentration (MIC) of ZnO nanoparticles against E. coli was found between 8 and 32 µg/ml, while for CuO nanoparticles, it ranged from 4 to 16 µg/ml. In vivo study results showed significant improvements in the treatment groups’ live body weight, carcass weight, and feed conversion ratio. Gross pathological examination revealed normal organs in treated groups. Biochemical analysis indicated reduced levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), urea, and creatinine in treated groups. Histopathological examination showed a significant decrease in congestion and leukocyte infiltration areas in treated groups compared to the control positive group. ZnO-CuO NPs at the rate of 25 + 10 mg/kg exhibited similar results to the antibiotic group, suggesting their potential as antibiotic alternatives in combating colibacillosis.

The reproductive system poses distinct physiological challenges for effective drug delivery, necessitating innovative strategies to navigate various biological barriers, including the blood-testis barrier, vaginal mucosa, and cervix. Targeted drug delivery is essential for addressing prevalent conditions that require therapeutic intervention, such as reproductive cancers, infertility, and sexually transmitted infections. Recent advancements in drug delivery systems, particularly those utilizing nanotechnology, have demonstrated significant potential in enhancing the therapeutic efficacy of various agents. Platforms like nanoparticles and liposomes facilitate targeted drug delivery, whereas hydrogels and biodegradable polymers enable localized and controlled release of therapeutics. Innovations in injectable and implantable systems, such as drug-eluting intrauterine devices and subdermal implants, have further optimized sustained drug release mechanisms. Additionally, micro- and nano-needles offer minimally invasive methods for direct administration to reproductive tissues. Route-specific delivery methods, including vaginal, uterine, and penile applications, have been investigated to improve bioavailability and patient compliance. Moreover, targeted and precision medicine approaches, encompassing gene therapy and personalized medicine, are advancing tailored treatment protocols based on individual genetic and molecular profiles. The therapeutic landscape includes applications in assisted reproductive technologies and the management of reproductive cancers and infections, highlighting the transformative potential of advanced drug delivery systems to enhance patient outcomes. Nonetheless, considerations regarding safety and regulatory compliance remain paramount in the development and application of these innovative therapies, emphasizing the need for ongoing research in this critical domain of reproductive health.

In vitro models for drug delivery systems play a crucial role in pharmaceutical research by providing controlled environments to study the behavior and efficacy of drug formulations. These models typically involve simulated biological systems or tissues that allow researchers to assess drug release kinetics, stability, and interactions with biological barriers such as cell membranes. By mimicking physiological conditions in a controlled manner, in vitro models help in optimizing drug formulations for improved delivery efficiency and therapeutic outcomes. They are instrumental in screening potential drug candidates, assessing toxicity levels, and understanding mechanisms of drug absorption and distribution within the body. Overall, in vitro models serve as indispensable tools in developing and evaluating novel drug delivery systems, bridging the gap between early-stage research and clinical applications. This comprehensive review explores various in vitro models, including cell cultures, tissue explants, and organ-on-a-chip technologies, highlighting their applications, advantages, limitations, and prospects. Through understanding these models, researchers can enhance the design and efficacy of DDS, ultimately improving therapeutic outcomes.

This chapter discusses the evolving field of targeted drug delivery systems (TDDS) and drug delivery systems (DDS) focusing on strategies to enhance the solubility and targeted delivery of insoluble pharmaceutical compounds. Various techniques are explored including changes in pH and salt development, polymeric micelles, nanonization, liposomes, solid lipid nanoparticles, cocrystal preparation, and dendrimers. These strategies aim to overcome challenges such as poor solubility, rapid clearance, and limited bioavailability of drugs, ultimately improving therapeutic efficacy while reducing adverse effects. Additionally, tissue-specific selective drug transporting methods are highlighted, emphasizing the significance of tailored approaches for specific diseases. The chapter concludes by underscoring the significance of continued advancements in technologies related to drug delivery and their potential for novel therapeutic applications, as well as the significance of understanding receptor-ligand biology in translating targeted systems into clinical practice. Overall, the chapter provides a comprehensive overview of existing tactics and potential future prospects in the area of pharmaceuticals delivery, emphasizing the need for precision medicine approaches to improve patient outcomes.

Cancer remains a global health challenge, with 19.3 million new cases and 10 million cancer-related deaths reported in 2020. Despite advancements in radiation, chemotherapy, and surgical treatments, limitations such as poor drug specificity, toxicity, and resistance hinder their effectiveness. Emerging strategies, including the development of smart drug delivery systems (SDDS) and tumor-homing peptides, offer a promising alternative by enhancing drug efficacy while minimizing side effects. Tumor-homing peptides, through selective targeting and internalization, enable precise delivery of therapeutic agents to tumor cells, improving therapeutic outcomes. Nanotechnology has further revolutionized drug delivery systems, providing stimuli-responsive platforms for enhanced targeting. Additionally, the tumor microenvironment (TME) has been recognized as a crucial factor influencing cancer progression and therapy response. This chapter highlights the role of peptides in addressing key challenges in cancer therapy, including targeting tumor vasculature, extracellular matrix, lymphatic vessels, and cell membranes, while also presenting innovative strategies for drug delivery and therapeutic intervention.

The interest in employing cell components as well as metabolites obtained from varied probiotic strains is increasing because of the growing concern regarding safety issues related to live microbial cells. Numerous benefits over conventional probiotics will facilitate the implementation of postbiotics as feed supplements in poultry nutrition. The beneficial characteristics, such as immunomodulation and antibacterial action, point to the possibility of postbiotics improving host health by altering the physiology of the host and ameliorating the disease condition in poultry. As we proceed forward with the ultimate aim of lowering antibiotic use in poultry, maximising performance and maintaining poultry production will be reliant on the best mixes of diverse alternatives as postbiotics, together with appropriate farm management practices. Trials with emphasis on validating the health claims made by these bioactive compounds are highly necessary. Furthermore, the employment of postbiotics under challenging conditions in poultry needs to be explored. This review focuses on highlighting the aspects about postbiotics and its various biological effects on meat and egg production in the poultry industry.

Pharmacokinetics, a subfield of pharmacology, is the study of drug absorption, distribution, metabolism, and excretion kinetics, including the magnitude and speed of each of these processes. The Greek elements “pharmakon” (drug) and “kinesis” (movement) are the origin of the English term “pharmacokinetics,” which describes the movement of a drug. Pharmacokinetics is the mathematical study of the time dependent variation in medication concentrations. So, to sum up, pharmacokinetics is the study of how medications enter, travel through, and are eliminated from the body by means of metabolism and excretion. Pharmaceuticals depend on pharmacokinetics research since it determines the dosage, mode of administra�tion, time of peak effect, duration of action, and frequency of drug administration. Principles of pharmaco�kinetics center on variations in drug concentration brought about by drug absorption, distribution, and elimination throughout time. There are two primary ways that drugs and chemicals get beyond biological membranes: simple transfer and specialized transport. The process by which an unaltered medication enters the bloodstream from the place of administration is known as absorption. Due to the porosity of the capillaries, even big lipid-insoluble or ionized medicines are absorbed, whereas lipid-soluble medications readily pass through the capillary endothelium. The process by which medications enter extravascular fluids and tissues and leave the bloodstream is known as distribution. This critical pharmacokinetic phase affects not only the organs involved in metabolism and excretion but also the way that medicines reach their target areas. The process of changing a substance’s chemical form to one that is more water soluble for simpler excretion is called metabolism. Particularly, “biotransformation” describes the chemical alterations that foreign substances go through in the body. There are two main stages of biotransformation. Phase I consists of processes involving oxidation, reduction, and hydrolysis that add or reveal tiny polar functional groups (such -OH and -NH2). In order to prepare lipid-soluble medications for Phase II reactions or direct excretion, this phase alters them to make them more polar. Conjugation is the process by which polar endogenous compounds (such as sulfate or glucuronic acid) are joined to medications or their Phase I metabolites in Phase II. This step results in readily excreted conjugates that are soluble in water. The process of permanently eliminating medications and their metabolites from the body is called excretion. Water soluble and ionized compounds are excreted more readily by excretory organs—apart from the lungs—than lipid-soluble ones, which must first be converted into water-soluble forms in order to be excreted more easily. The drug’s concentration in the body has an impact on pharmacokinetic processes (ADME), and how that concentration influences the process rate is known as the process order. Key pharmacokinetic parameters may be computed and the time course of medications in the body can be expressed quantitaively using pharmacokinetic models. Pharmacokinetics is determined by three factors: elimination, distribution and absorption.

Recent advancements in molecular pharmacology and a deepened understanding of disease mechanisms have emphasized the need to precisely target specific cells responsible for disease onset and progression to prevent side effects and minimize systemic exposure. Drug delivery (DD) involves the strategies, formulations, technologies, and procedures employed to transport a pharmaceutical substance within the body of both humans and animals to produce the intended therapeutic outcome. The most frequently used delivery methods include topical (applied to the skin), transmucosal (such as nasal, buccal, sublingual, vaginal, ocular, and rectal), and inhalation routes. Traditional dosage forms release the drug rapidly, which can lead to variations in blood drug levels depending on the form of dosage. Current drug delivery systems (DDS) leverage cutting-edge technology to expedite the delivery of drugs systemically to specific target sites, thereby maximizing therapeutic efficacy while minimizing unintended accumulation in the body. Consequently, they play a pivotal role in disease management and treatment. Modern DDS present distinct advantages over conventional delivery systems, owing to their superior performance, automation, precision, and effectiveness. Utilizing nanomaterials or small-scale devices with multifunctional components, these systems are characterized by biocompatibility, biodegradability, and high viscoelasticity, resulting in prolonged circulating half-lives. This chapter offers a comprehensive overview of drug delivery systems’ historical progression and technological evolution. It also delves into recent developments in DDS, their therapeutic applications, challenges in their use, and potential future improvements for enhanced performance and utilization.

Traditional drug delivery methods (tablets, capsules, syrups, ointments, etc.) are not able to produce sustained release and have low bioavailability along with changes in plasma drug level. The entire therapy process may be pointless in the absence of an effective delivery of the system. The drug must also be delivered at a precise target spot at a predetermined controlled pattern to achieve optimal efficacy and safety. Many aspects of therapeutic efficacy, like pharmacokinetics, distribution, absorption into cells and metabo lism, excretion and clearance, and toxicity, are impacted by the route of delivery. Both innovative delivery systems and a greater understanding of the basic principles underlying how drug distribution influences safety and efficacy are required as the biotechnology sector develops novel kinds of biopharmaceuticals. Drug resistance is still an ongoing issue though, mostly owing to our incomplete knowledge of the biological barriers that prevent many drugs from reaching their intended targets. Despite the significant advantages of immunotherapy, off-target effects continue to cause serious adverse immune reactions. Recently, the research and development of drug delivery systems (DDS) have gained increased attention. Over decades of innovation, DDS has proven effective in delivering drugs with precision, thereby reducing side effects. They also offer benefits such as flexible control over drug release, improved pharmacokinetics, and enhanced drug distribution. Therefore, in this book chapter, a detailed overview of combining the approach of immunotherapies and vaccines with drug delivery systems is discussed to improve the thera peutic effect.

The study aimed to investigate the assessment of farm profiles, knowledge gain, and adoption behaviours of biosecurity practices following a training intervention in commercial poultry farms in Tamil Nadu. A total of 89 farmers from commercial desi (32), layer (30), and broiler (27) farms participated in the training program. The biosecurity assessment used an evaluation framework with a two‐day training program. Participants completed pre‐ and post‐training surveys to measure knowledge gained during the training. Additionally, we conducted a follow‐up evaluation of adoption behaviours after 90 days of training intervention. Questionnaire data were analysed using paired sample t‐test, chi‐square, and regression analysis. Results revealed that 89% of the trainees were male, 90% were in the age group between 21 and 60 years, and 88% had a secondary education level or higher. Further, 56.2% of farmers had 5–20 years of experience in poultry farming, and 46.1% of farmers revealed that the significant source of income is from poultry farming and agricultural practices. A pre‐ and post‐survey data comparison showed that all the farmers had significant knowledge gain (p < 0.01) in all the categories of structural and operational biosecurity practices immediately after the training. The farmer's educational qualification significantly influences the knowledge gain except for dead bird disposal (p < 0.05). Commercial desi and layer farmers have more pre‐existing knowledge compared to broiler farmers. The broiler farmers showed the highest knowledge gain compared to layer and commercial desi farmers. Still, there was no significant difference between knowledge gain among different types of poultry farmers (p > 0.05). The adoption behaviour measured after 90 days significantly increased in all categories (p < 0.05) except for rodent and pest control. This comprehensive study provided valuable insights regarding farmers’ existing knowledge and the impact of training on some behavioural changes to improve biosecurity. The study concluded that a tailored training program is essential to educate small‐scale producers about biosecurity measures to prevent poultry food‐borne diseases.

Bovine tuberculosis (bTB) is a severe infectious disease that affects both domesticated and wild animals and has a negative impact on both public health and the global economy. The causative organism of the disease is Mycobacterium bovis and, sporadically, other pathogenic mycobacteria. The issue of bTB is made more challenging when the infection is linked to multi-drug resistant M. bovis. In the current investigation, immunoinformatics approach has been applied to design a multiepitope peptide-based vaccine, MBOVAC1.0. Based on an initial screening of 3805 proteins, we selected three vital proteins viz., PPE family protein, ESAT-6 and Serine Threonine Protein Kinase for designing the multi-epitope vaccine candidate. The candidate vaccine elicited strong expression in Escherichia coli following codon optimization and in silico cloning. Immunological simulation result indicated release of immune molecules by CD4 + and CD8 + T-lymphocytes and antibodies by B-lymphocytes ensuring in high level of both cell mediated and humoral immunity against the pathogen. The proposed vaccine candidate was found to yield encouraging results in terms of safety, stability, antigenicity and immunogenicity; so, it should be validated by wet lab experiments to assess its efficacy in neutralising bTB. Supplementary Information The online version contains supplementary material available at https:// doi.

Alpha-synucleinopathies, characterized by extracellular alpha-synuclein (αSyn or SNCA) accumulation and aggregation, have been linked to neurological disorders including Parkinson’s disease and multiple system atrophy. P2RX7 is a non-selective cationic transmembrane purinergic receptor activated by elevated levels of extracellular ATP, which typically occurs during inflammatory conditions. Activation of P2RX7 by αSyn is implicated in neuronal degeneration, potentially causing pore dilation and increased inflammation. By integrating the data curation, molecular docking, and molecular dynamics (MD) simulations, along with structural analyses, we attempted to elucidate the molecular mechanisms and binding sites for P2RX7-αSyn interaction. We elucidated interactions between P2RX7 and the N-terminal domain (NTD) of αSyn. Utilizing cryo-EM structures of P2RX7 in ATP-bound and unbound states, we assessed αSyn’s effect on P2RX7 structural and functional dynamics. Initially, the analyses revealed that αSyn interactomes are mainly involved in mitochondrial functions, while P2RX7 interactors are linked to receptor internalization and calcium transport. Molecular docking with six tools identified that αSyn-NTD fragments preferentially bind to the proximal region of P2RX7’s transmembrane domain. Microsecond all atom MD simulations in a POPS lipid bilayer showed significant atomic fluctuations, particularly in the head region, lower body, and large loop of P2RX7’s cytoplasmic domain. Secondary structure analysis indicated unfolding in regions related to pore dilation and receptor desensitization. Further by contact-based and solvent accessibility analyses, along with protein structure network (PSN) studies, we identified crucial residues involved in αSyn-P2RX7 interactions. This understanding enhances the knowledge of how αSyn and P2RX7 interactions take place, potentially contributing to neurodegenerative diseases, and could be instrumental in developing future preventive and therapeutic approaches.

The acquisition of suitable stem cell sources is a significant issue in regenerative medicine. There has been considerable interest in utilizing mesenchymal stem cells (MSCs) derived from endometrial and menstrual blood as a promising resource of MSCs, owing to their unique biochemical properties and prospective use in clinical therapies. This population of stem cells has distinct characteristics in terms of immunophenotype, proliferation rate, and differentiation capacity. A notable characteristic of these stem cells is their capacity to develop into mesodermal lineages, highlighting their regenerative capability. Moreover, the presence of certain surface markers facilitates the augmentation of clonogenic endometrial MSCs. Their distinctive characteristics, along with their swift multiplication ability, underscore their significant promise for therapeutic applicability in regenerative medicine and cell-based treatments. Current investigations are examining possible usage of diverse stem cell resources in the treatment of inflammatory diseases and perhaps intractable illnesses like Parkinson's disease, utilizing their immunomodulatory properties. This review aims to analyze stem cell-related research that has utilized endometrial and menstrual blood-derived MSCs (enMSCs and MenSCs) with a special focus on their clinical application. We will explore the existing evidence about the therapeutic potential for these stem cells across many medical diseases and address the obstacles and prospective trajectories in this domain. Additionally, we will study the unique properties of enMSCs and MenSCs that make them promising candidates for regenerative medicine.