Comparative transcriptome analysis of E. coli & Staphylococcus aureus infected goat mammary epithelial cells reveals genes associated with infection.

Mastitis, an inflammatory disease of the mammary gland, imposes a significant financial burden on the dairy sector. However, the specific molecular mechanisms underlying their interactions with goat mammary epithelial cells (GMECs) remain poorly understood. This study aimed to investigate the transcriptomic response of GMECs during infection with E. coli and S. aureus, providing insights into the host-pathogen interactions. Differential expression of gene (DEGs) analysis was done to find genes and pathways dysregulated in the wake of infection. E. coli infection triggered a robust upregulation of immune response genes, including pro-inflammatory chemokines and cytokines as well as genes involved in tissue repair and remodeling. Conversely, S. aureus infection showed a more complex pattern, involving the activation of immune-related gene as well as those involved in autophagy, apoptosis and tissue remodeling. Furthermore, several key pathways, such as Toll-like receptor signaling and cytokine-cytokine receptor interaction, were differentially modulated in response to each pathogen. Understanding the specific responses of GMECs to these pathogens will provide a foundation for understanding the complex dynamics of infection and host response, offering potential avenues for the development of novel strategies to prevent and treat bacterial infections in both animals and humans.

PM2.5 Exposure-Linked Mitochondrial Dysfunction Negates SB216763-Mediated Cardio-Protection against Myocardial Ischemia-Reperfusion Injury.

GSK3ß is a promising target for treating various disease conditions, including myocardial ischemia-reperfusion injury (IR). This study investigated the potential of GSK3ß as a novel drug for managing IR in rats exposed to PM2.5 for 1 day and up to 21 days. Female Wistar rats were exposed to PM2.5 at a concentration of 250 µg/m3 for 3 h daily for either a single day or 21 days. After exposure, the isolated rat hearts underwent 30 min of ischemia followed by 60 min of reperfusion. GSK3ß inhibition effectively reduced IR injury in rat hearts from animals exposed to PM2.5 for 1 day but not in those exposed for 21 days. PM2.5 exposure disrupted the redox balance in mitochondria and reduced the gene expression of antioxidants (glutaredoxin and peroxiredoxin) and NRF2, which protects against oxidative stress. PM2.5 also impaired mitochondrial bioenergetics, membrane potential, and quality control, leading to mitochondrial stress. Importantly, PM2.5 increased the translocation of GSK3ß into mitochondria and compromised the overall mitochondrial function, particularly in the 21-day-exposed rat myocardium. The results indicate that extended exposure to PM2.5 leads to oxidative stress that disrupts mitochondrial function and diminishes the effectiveness of GSK3ß inhibitors in offering cardio-protection through mitochondria.

Identification of SNPs Related to Salmonella Resistance in Chickens Using RNA-Seq and Integrated Bioinformatics Approach.

Potential single nucleotide polymorphisms (SNPs) were detected between two chicken breeds (Kashmir favorella and broiler) using deep RNA sequencing. This was carried out to comprehend the coding area alterations, which cause variances in the immunological response to Salmonella infection. In the present study, we identified high impact SNPs from both chicken breeds in order to delineate different pathways that mediate disease resistant/susceptibility traits. Samples (liver and spleen) were collected from Salmonella resistant (K. favorella) and susceptible (broiler) chicken breeds. Salmonella resistance and susceptibility were checked by different pathological parameters post infection. To explore possible polymorphisms in genes linked with disease resistance, SNP identification analysis was performed utilizing RNA seq data from nine K. favorella and ten broiler chickens. A total of 1778 (1070 SNPs and 708 INDELs) and 1459 (859 SNPs and 600 INDELs) were found to be specific to K. favorella and broiler, respectively. Based on our results, we conclude that in broiler chickens the enriched pathways mostly included metabolic pathways like fatty acid metabolism, carbon metabolism and amino acid metabolism (Arginine and proline metabolism), while as in K. favorella genes with high impact SNPs were enriched in most of the immune-related pathways like MAPK signaling pathway, Wnt signaling pathway, NOD-like receptor signaling pathway, etc., which could be a possible resistance mechanism against salmonella infection. In K. favorella, protein-protein interaction analysis also shows some important hub nodes, which are important in providing defense against different infectious diseases. Phylogenomic analysis revealed that indigenous poultry breeds (resistant) are clearly separated from commercial breeds (susceptible). These findings will offer fresh perspectives on the genetic diversity in chicken breeds and will aid in the genomic selection of poultry birds.

Identification of key transcription factors and their functional role involved in Salmonella typhimurium infection in chicken using integrated transcriptome analysis and bioinformatics approach.

Salmonella enterica serovar typhimurium is the cause of significant morbidity and mortality worldwide that causes economic losses to poultry and is able to cause infection in humans. Indigenous chicken breeds are a potential source of animal protein and have the added advantage of being disease resistant. An indigenous chicken, Kashmir favorella and commercial broiler were selected for understanding the mechanism of disease resistance. Following infection in Kashmir favorella, three differentially expressed genes Nuclear Factor Kappa B (NF-κB1), Forkhead Box Protein O3 (FOXO3) and Paired box 5 (Pax5) were identified. FOXO3, a transcriptional activator, is the potential marker of host resistance in Salmonella infection. NF-κB1 is an inducible transcription factor which lays the foundation for studying gene network of the innate immune response of Salmonella infection in chicken. Pax5 is essential for differentiation of pre-B cells into mature B cell. The real time PCR analysis showed that in response to Salmonella Typhimurium infection a remarkable increase of NF-κB1 (P˂0.01), FOXO3 (P˂0.01) gene expression in liver and Pax5 (P˂0.01) gene expression in spleen of Kashmir favorella was observed. The protein-protein interaction (PPI) and protein-TF interaction network by STRINGDB analysis suggests that FOXO3 is a hub gene in the network and is closely related to Salmonella infection along with NF-κB1. All the three differentially expressed genes (NF-κB1, FOXO3 and PaX5) showed their influence on 12 interacting proteins and 16 TFs, where cyclic adenosine monophosphate Response Element Binding protein (CREBBP), erythroblast transformation-specific (ETSI), Tumour-protein 53(TP53I), IKKBK, lymphoid enhancer-binding factor-1 (LEF1), and interferon regulatory factor-4 (IRF4) play role in immune responses. This study shall pave the way for newer strategies for treatment and prevention of Salmonella infection and may help in increasing the innate disease resistance.

Oral contraceptive pill (OCP) treatment alters the gene expression of intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1) in polycystic ovary syndrome (PCOS) women compared to drug-naive PCOS women.

BACKGROUND: Polycystic ovary syndrome (PCOS) presents clinical symptoms of menstrual abnormalities, excessive hair growth (hirsutism), scalp hair loss, acne and infertility. Metabolic abnormalities such as obesity, insulin resistance, glucose intolerance and cardiovascular problems constitute an essential part of PCOS, all of which can have significant long-term health consequences. Low-grade chronic inflammation demonstrated by persistent moderately elevated serum levels of inflammatory and coagulatory markers plays a critical role in the pathogenesis of PCOS. Oral contraceptive pills (OCPs) constitute the mainstay of pharmacologic therapy for women with PCOS to regularize cyclicity and ameliorate androgen excess. On the other hand, OCP use is associated with various venous thromboembolic and proinflammatory events in the general population. PCOS women always carriers the increased lifetime risk of these events. The studies on the effect of OCPs on inflammatory, coagulation and metabolic parameters in PCOS are less robust. Therefore in this study, we investigated and compared the messenger RNA (mRNA) expression profiles of genes implicated in inflammatory and coagulation pathways between drug-naive and OCP-treated PCOS women. The selected genes include intercellular adhesion molecule-1 (ICAM-1), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator inhibitor-1 (PAI-1). Furthermore, the correlation between the selected markers and various metabolic indices in the OCP group has also been explored. METHOD: The relative amounts of ICAM-1, TNF-α, MCP-1 and PAI-1 mRNA in peripheral blood mononuclear cells from 25 drug-naive PCOS subjects (controls) and 25 PCOS subjects who received OCPs containing 0.03 mg-ethinyl-estradiol and 0.15 mg-levonorgestrel for at least six months (cases) were estimated using real-time qPCR. The statistical interpretation was conducted using SPSS version 20.0 (SPSS, Inc, Chicago, IL), Epi Info version 2002 (Disease Control and Prevention Centres, Atlanta, GA) and GraphPad Prism 5 (GraphPad Software, La Jolla, CA) software. RESULT: Six months of OCP therapy enhanced the expression of inflammatory genes viz ICAM-1, TNF-α and MCP-1 mRNA in PCOS women by 2.54, 2.05 and 1.74 folds, respectively, in this study. However, PAI-1 mRNA in the OCP group showed no significant increase. Furthermore, in cases, ICAM-1 mRNA expression positively correlated with body mass index (BMI) (p = 0.01), fasting insulin (p = 0.01), insulin 2 h p = 0.02), glucose 2 h (p = 0.01) and triglycerides (p = 0.01). TNF-α mRNA expression positively correlated with fasting insulin (p = 0.0007). MCP-1 mRNA expression positively correlated with (BMI) (p = 0.002). CONCLUSION: OCPs helped reduce clinical hyperandrogenism and regularise menstrual cycles in women with PCOS. However, OCP use was associated with increased fold expression of inflammatory markers which positively correlated with metabolic abnormalities.

Multiomics technologies: role in disease biomarker discoveries and therapeutics.

Medical research has been revolutionized after the publication of the full human genome. This was the major landmark that paved the way for understanding the biological functions of different macro and micro molecules. With the advent of different high-throughput technologies, biomedical research was further revolutionized. These technologies constitute genomics, transcriptomics, proteomics, metabolomics, etc. Collectively, these high-throughputs are referred to as multi-omics technologies. In the biomedical field, these omics technologies act as efficient and effective tools for disease diagnosis, management, monitoring, treatment and discovery of certain novel disease biomarkers. Genotyping arrays and other transcriptomic studies have helped us to elucidate the gene expression patterns in different biological states, i.e. healthy and diseased states. Further omics technologies such as proteomics and metabolomics have an important role in predicting the role of different biological molecules in an organism. It is because of these high throughput omics technologies that we have been able to fully understand the role of different genes, proteins, metabolites and biological pathways in a diseased condition. To understand a complex biological process, it is important to apply an integrative approach that analyses the multi-omics data in order to highlight the possible interrelationships of the involved biomolecules and their functions. Furthermore, these omics technologies offer an important opportunity to understand the information that underlies disease. In the current review, we will discuss the importance of omics technologies as promising tools to understand the role of different biomolecules in diseases such as cancer, cardiovascular diseases, neurodegenerative diseases and diabetes.

Nanogel-based Transdermal Drug Delivery System: A Therapeutic Strategy with Under Discussed Potential.

The application of nanoparticles in medication delivery has revolutionized the field of therapeutic biology. To improve medical efficacy, currently, drug nanocarriers are employed to control the release and stability, expand its circulation time, or protect it from cell clearance or premature breakdown. A crosslinked polymeric framework is used to crosslink the hydrogel nanoparticle dispersions for safer and stable delivery on target sites. Nanogels have developed in the last two decades as potential biomaterials with a wide variety of applications. Later attributes of nanogels are mainly due to large surface areas, retention of molecules, size flexibility, and water-based formulations that have made them popular as drug delivery vehicles, as seen by several in vivo uses. The gel matrix containing the nanoparticle drug demonstrated a considerable increase in drug penetration in transdermal drug and topical delivery methods. This review aims to understand why and how nanogels are considered so innovative as a drug delivery method. It also examines their preparation methods and applications in the pharmaceutical and biomedical fields and discusses the benefits of nanogels, including swelling capacity and stimulus stimuli sensitivity. Nanogels, on the other hand, have recently been investigated for applications outside the field of biomedicine. Since there are many possible uses for nanogels, we have comprehensively reviewed the current state of the art for all feasible nanogel applications and manufacturing methods.

Comparative RNA-Seq analysis reveals insights in Salmonella disease resistance of chicken; and database development as resource for gene expression in poultry.

Salmonella, one of the major infectious diseases in poultry, causes considerable economic losses in terms of mortality and morbidity, especially in countries that lack effective vaccination programs. Besides being resistant to diseases, indigenous chicken breeds are also a potential source of animal protein in developing countries. For understanding the disease resistance, an indigenous chicken line Kashmir faverolla, and commercial broiler were selected. RNA-seq was performed after challenging the chicken with Salmonella Typhimurium. Comparative differential expression results showed that following infection, a total of 3153 genes and 1787 genes were differentially expressed in the liver and spleen, respectively. The genes that were differentially expressed included interleukins, cytokines, NOS2, Avß-defensins, toll-like receptors, and other immune-related gene families. Most of the genes and signaling pathways involved in the innate and adaptive immune responses against bacterial infection were significantly enriched in the Kashmir faverolla. Pathway analysis revealed that most of the enriched pathways were MAPK signaling pathway, NOD-like receptor signaling pathway, TLR signaling pathway, PPAR signaling pathway, endocytosis, etc. Surprisingly some immune-related genes like TLRs were upregulated in the susceptible chicken breed. On postmortem examination, the resistant birds showed small lesions in the liver compared to large necrotic lesions in susceptible birds. The pathological manifestations and RNA sequencing results suggest a balancing link between resistance and infection tolerance in Kashmir faverolla. Here we also developed an online Poultry Infection Database (https://skuastk.org/pif/index.html), the first publicly available gene expression resource for disease resistance in chickens. The available database not only shows the data for gene expression in chicken tissues but also provides quick search, visualization and download capacity.

Nutrigenomics in livestock sector and its human-animal interface-a review.

Noncommunicable diseases such as cardiovascular disease, obesity, diabetes, and cancer now outnumber all other health ailments in humans globally due to abrupt changes in lifestyle following the industrial revolution. The industrial revolution has also intensified livestock farming, resulting in an increased demand for productivity and stressed animals. The livestock industry faces significant challenges from a projected sharp increase in global food and high animal protein demand. Nutrition genomics holds great promise for the future as its advances have opened up a whole new world of disease understanding and prevention. Nutrigenomics is the study of the interactions between genes and diet. It investigates molecular relationships between nutrients and genes to identify how even minor modifications could potentially alter animal and human health/performance by using techniques like proteomics, transcriptomics, metabolomics, and lipidomics. Dietary modifications mostly studied in livestock focus mainly on health and production traits through protein, fat, mineral, and vitamin supplementation changes. Nutrigenomics meticulously selects nutrients for fine-tuning the expression of genes that match animal/human genotypes for better health, productivity, and the environment. As a step forward, nutrigenomics integrates nutrition, molecular biology, genomics, bioinformatics, molecular medicine, and epidemiology to better understand the role of food as an epigenetic factor in the occurrence of these diseases. This review aims to provide a comprehensive overview of the fundamental concepts, latest advances, and studies in the field of nutrigenomics, emphasizing the interaction of diet with gene expression, and how it relates to human and animal health along with its human-animal interphase.

Pathogenesis-Related Gene Expression in Response to Trachyspermum ammi Supplementation Along With Probiotics in Chicken Salmonellosis and Insights in Drug Therapeutics.

Salmonella enterica serovar typhimurium (S. typhimurium) is the leading cause of foodborne illness. Since Salmonella continues to have a detrimental effect on public health, there is an ongoing need to develop more advanced methods for combating Salmonellosis in foods before they reach consumers. In addition, the quest for alternative natural products has recently intensified due to increasingly stringent regulations regarding the use of antibiotics as growth promoters and consumer demand for antibiotic-free poultry products. This study evaluated the effect of Ajwain extract (AJE) on immune response and antioxidant status in broiler chicks challenged with Salmonella typhimurium. The chicks were infected with S. typhimurium and were divided into the different groups, except for the control group (CON). The challenged chicks received different treatments with 3 × 109 colony-forming unit (CFU) AciproTM-WS probiotic (PRO), 200 mg/kg Ajwain extract (AJE), 200 mg/100 kg of enrofloxacin (ENR), and a combination of 3 × 109 CFU AciproTM-WS probiotic and 200 mg/kg Ajwain extract (COM). Five days posttreatment, the tissue samples (liver and spleen) were analyzed. The results showed that basal diet supplemented with Ajwain extract (AJE) and a combination of probiotic and Ajwain extract (COM) significantly (P < 0.0.5) reduced the cytokine expression in broiler chicks challenged with S. typhimurium. Our findings suggest that AJE can clear the bacterial infection, improve antioxidant status, and suppress the inflammation response. Additionally, AJE supplementation significantly mitigated the S. typhimurium-induced increase in the interleukin-6 (IL-6) (liver and spleen), interleukin-8 (IL-8) (liver and spleen), interleukin-17A (IL-17A) (liver and spleen), and inducible nitric oxide (iNOS) (spleen and liver) levels (P < 0.05). We conclude that Ajwain is an efficient feed additive with antioxidant and anti-inflammatory properties. The interaction networks developed in this study provide a novel lead that could be targeted for anti-inflammatory and antioxidant properties.

Mammary epithelial cell transcriptome reveals potential roles of lncRNAs in regulating milk synthesis pathways in Jersey and Kashmiri cattle.

BACKGROUND: Long noncoding RNAs (lncRNAs) are now proven as essential regulatory elements, playing diverse roles in many biological processes including mammary gland development. However, little is known about their roles in the bovine lactation process. RESULTS: To identify and characterize the roles of lncRNAs in bovine lactation, high throughput RNA sequencing data from Jersey (high milk yield producer), and Kashmiri cattle (low milk yield producer) were utilized. Transcriptome data from three Kashmiri and three Jersey cattle throughout their lactation stages were utilized for differential expression analysis. At each stage (early, mid and late) three samples were taken from each breed. A total of 45 differentially expressed lncRNAs were identified between the three stages of lactation. The differentially expressed lncRNAs were found co-expressed with genes involved in the milk synthesis processes such as GPAM, LPL, and ABCG2 indicating their potential regulatory effects on milk quality genes. KEGG pathways analysis of potential cis and trans target genes of differentially expressed lncRNAs indicated that 27 and 48 pathways were significantly enriched between the three stages of lactation in Kashmiri and Jersey respectively, including mTOR signaling, PI3K-Akt signaling, and RAP1 signaling pathways. These pathways are known to play key roles in lactation biology and mammary gland development. CONCLUSIONS: Expression profiles of lncRNAs across different lactation stages in Jersey and Kashmiri cattle provide a valuable resource for the study of the regulatory mechanisms involved in the lactation process as well as facilitate understanding of the role of lncRNAs in bovine lactation biology.

Genome wide expression analysis of circular RNAs in mammary epithelial cells of cattle revealed difference in milk synthesis.

Milk is an excellent source of nutrients for humans. Therefore, in order to enhance the quality and production of milk in cattle, it is interesting to examine the underlying mechanisms. A number of new investigations and research have found that, circRNA; a specific class of non-coding RNAs, is linked with the development of mammary gland and lactation. In the present study, genome wide identification and expression of the circRNAs in mammary epithelial cells of two distinct cattle breeds viz Jersey and Kashmiri at peak lactation was conducted. We reported 1554 and 1286 circRNA in Jersey and Kashmiri cattle, respectively, with 21 circRNAs being differentially expressed in the two breeds. The developmental genes of the established differentially expressed circRNAs were found to be largely enriched in antioxidant activity, progesterone, estradiol, lipid, growth hormone, and drug response. Certain pathways like MAPK, IP3K and immune response pathways were found significantly enriched in KEGG analysis. These results add to our understanding of the controlling mechanisms connected with the lactation process, as well as the function of circRNAs in bovine milk synthesis. Additionally, the comparative analysis of differentially expressed circRNAs showed significant conservation across different species.

Expression of lncRNAs in response to bacterial infections of goat mammary epithelial cells reveals insights into mammary gland diseases.

Mastitis or inflammation of the mammary gland is a highly economic and deadly alarming disease for the dairy sector as well as policymakers caused by microbial infection. Transcriptomic and proteomic approaches have been widely employed to identify the underlying molecular mechanisms of bacterial infections in the mammary gland. Numerous differentially expressed mRNAs, miRNAs, and proteins together with their associated signaling pathways have been identified during bacterial infection, paving the way for analysis of their biological functions. Long noncoding RNAs (lncRNAs) are important regulators of multiple biological processes. However, little is known regarding their role in bacterial infection in mammary epithelial cells. Hence, RNA-sequencing was performed by infecting primary mammary epithelial cells (pMECs) with both gram-negative (E. coli) and gram-positive bacteria (S. aureus). Using stringent pipeline, a set of 1957 known and 1175 novel lncRNAs were identified, among which, 112 lncRNAs were found differentially expressed in bacteria challenged PMECs compared with the control. Additionally, potential targets of the lncRNAs were predicted in cis- and trans-configuration. KEGG analysis revealed that DE lncRNAs were associated with at least 15 immune-related pathways. Therefore, our study revealed that bacterial challenge triggers the expression of lncRNAs associated with immune response and defense mechanisms in goat mammary epithelial cells.

Deep Insights in Circular RNAs: from biogenesis to therapeutics.

ABSTRACT: Circular RNAs (circRNAs) have emerged as a universal novel class of eukaryotic non-coding RNA (ncRNA) molecules and are becoming a new research hotspot in RNA biology. They form a covalent loop without 5' cap and 3' tail, unlike their linear counterparts. Endogenous circRNAs in mammalian cells are abundantly conserved and discovered so far. In the biogenesis of circRNAs exonic, intronic, reverse complementary sequences or RNA-binding proteins (RBPs) play a very important role. Interestingly, the majority of them are highly conserved, stable, resistant to RNase R and show developmental-stage/tissue-specific expression. CircRNAs play multifunctional roles as microRNA (miRNA) sponges, regulators of transcription and post-transcription, parental gene expression and translation of proteins in various diseased conditions. Growing evidence shows that circRNAs play an important role in neurological disorders, atherosclerotic vascular disease, and cancer and potentially serve as diagnostic or predictive biomarkers due to its abundance in various biological samples. Here, we review the biogenesis, properties, functions, and impact of circRNAs on various diseases.

Comparative transcriptome analysis of mammary epithelial cells at different stages of lactation reveals wide differences in gene expression and pathways regulating milk synthesis between Jersey and Kashmiri cattle.

Jersey and Kashmiri cattle are important dairy breeds that contribute significantly to the total milk production of the Indian northern state of Jammu and Kashmir. The Kashmiri cattle germplasm has been extensively diluted through crossbreeding with Jersey cattle with the goal of enhancing its milk production ability. However, crossbred animals are prone to diseases resulting to unsustainable milk production. This study aimed to provide a comprehensive transcriptome profile of mammary gland epithelial cells at different stages of lactation and to find key differences in genes and pathways regulating milk traits between Jersey and Kashmiri cattle. Mammary epithelial cells (MEC) isolated from milk obtained from six lactating cows (three Jersey and three Kashmiri cattle) on day 15 (D15), D90 and D250 in milk, representing early, mid and late lactation, respectively were used. RNA isolated from MEC was subjected to next-generation RNA sequencing and bioinformatics processing. Casein and whey protein genes were found to be highly expressed throughout the lactation stages in both breeds. Largest differences in differentially expressed genes (DEG) were between D15 vs D90 (1,805 genes) in Kashmiri cattle and, D15 vs D250 (3,392 genes) in Jersey cattle. A total of 1,103, 1,356 and 1,397 genes were differentially expressed between Kashmiri and Jersey cattle on D15, D90 and D250, respectively. Antioxidant genes like RPLPO and RPS28 were highly expressed in Kashmiri cattle. Differentially expressed genes in both Kashmiri and Jersey were enriched for multicellular organismal process, receptor activity, catalytic activity, signal transducer activity, macromolecular complex and developmental process gene ontology terms. Whereas, biological regulation, endopeptidase activity and response to stimulus were enriched in Kashmiri cattle and, reproduction and immune system process were enriched in Jersey cattle. Most of the pathways responsible for regulation of milk production like JAK-STAT, p38 MAPK pathway, PI3 kinase pathway were enriched by DEG in Jersey cattle only. Although Kashmiri has poor milk production efficiency, the present study suggests possible physicochemical and antioxidant properties of Kashmiri cattle milk that needs to be further explored.

Gene expression and antibody response in chicken against Salmonella Typhimurium challenge.

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a primary avian pathogen responsible for severe intestinal pathology in younger chickens and economic losses to poultry industry. Furthermore, S. Typhimurium is also able to cause infection in humans, characterized by acute gastrointestinal disease. A study was conducted to investigate antibody response and expression kinetics of interferon gamma (IFNγ), interleukin (IL-12, and IL-18) genes in broiler chicken at 0, 1, 3, 5, 7, 9, 11, 13, and 15 D post infection following experimental infection of S. Typhimurium. Immunological studies showed higher titres of IgG and IgM in the infected group as compared to the age-matched un-infected control group. The Real-Time PCR-based gene expression analysis revealed significant increase of IFNγ, IL-12, and IL-18 mRNA levels in the infected group as compared to their respective controls (P < 0.05). The present study shall help in understanding the immune responses in birds, thus allowing development of more effective vaccines and vaccination strategies.

Expression kinetics of natural resistance associated macrophage protein (NRAMP) genes in Salmonella Typhimurium-infected chicken.

BACKGROUND: Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) is a zoonotic pathogen responsible for severe intestinal pathology in young chickens. Natural resistance-associated macrophage protein (NRAMP) family has been shown to be associated with resistance to intracellular pathogens, including Salmonella Typhimurium. The role of NRAMP proteins in macrophage defence against microbial infection has been ascribed to changes in the metal-ion concentrations inside the bacteria-containing phagosomes. The present study was conducted to investigate tissue-specific (liver, spleen and caecum) expression kinetics of NRAMP gene family (NRAMP1 and NRAMP2) in broilers from day 0 to day 15 after Salmonella Typhimurium challenge concomitant to clinical, blood biochemical and immunological parameters survey. RESULTS: Clinical symptoms appeared 4 days post-infection (dpi) in infected birds. Symptoms like progressive weakness, anorexia, diarrhoea and lowering of the head were seen in infected birds one-week post-infection. On postmortem examination, liver showed congestion, haemorrhage and necrotic foci on the surface, while as the spleen, lungs and intestines revealed congestion and haemorrhages. Histopathological alterations were principally found in liver comprising of necrosis, reticular endothelial hyperplasia along with mononuclear cell and heterophilic infiltration. Red Blood Cell (RBC) count, Haemoglobin (Hb) and Packed Cell Volume (PCV) decreased significantly (P < 0.05) in blood while heterophil counts increased up to 7 days post-infection. Serum glucose, aspartate transaminase (AST) and alanine transaminase (ALT) enzymes concentrations increased significantly throughout the study. A gradual increase of specific humoral IgG response confirmed Salmonella infection. Meanwhile, expression of NRAMP1 and NRAMP2 genes was differentially regulated after infection in tissues such as liver, spleen and caecum known to be the target of Salmonella Typhimurium replication in the chicken. CONCLUSION: Thus the specific roles of NRAMP1 and NRAMP2 genes in Salmonella Typhimurium induced disease may be supposed from their differential expression according to tissues and timing after per os infection. However, these roles remain to be analyzed related to the severity of the disease which can be estimated by blood biochemistry and immunological parameters.

LncRNAs and immunity: watchdogs for host pathogen interactions.

Immune responses combat various infectious agents by inducing inflammatory responses, antimicrobial pathways and adaptive immunity. The polygenic responses to these external stimuli are temporally and coordinately regulated. Specific lncRNAs are induced to modulate innate and adaptive immune responses which can function through various target interactions like RNA-DNA, RNA-RNA, and RNA-protein interaction and hence affect the immunogenic regulation at various stages of gene expression. LncRNA are found to be present in various immune cells like monocytes, macrophages, dendritic cells, neutrophils, T cells and B cells. They have been shown to be involved in many biological processes, including the regulation of the expression of genes, the dosage compensation and genomics imprinting, but the knowledge how lncRNAs are regulated and how they alter cell differentiation/function is still obscure. Further dysregulation of lncRNA has been seen in many diseases, but as yet very less research has been carried out to understand the role of lncRNAs in regulation during host-pathogens interactions. In this review, we summarize the functional developments and mechanism of action of lncRNAs, in immunity and defense of host against pathogens.

Long non-coding RNAs: Mechanism of action and functional utility.

Recent RNA sequencing studies have revealed that most of the human genome is transcribed, but very little of the total transcriptomes has the ability to encode proteins. Long non-coding RNAs (lncRNAs) are non-coding transcripts longer than 200 nucleotides. Members of the non-coding genome include microRNA (miRNA), small regulatory RNAs and other short RNAs. Most of long non-coding RNA (lncRNAs) are poorly annotated. Recent recognition about lncRNAs highlights their effects in many biological and pathological processes. LncRNAs are dysfunctional in a variety of human diseases varying from cancerous to non-cancerous diseases. Characterization of these lncRNA genes and their modes of action may allow their use for diagnosis, monitoring of progression and targeted therapies in various diseases. In this review, we summarize the functional perspectives as well as the mechanism of action of lncRNAs.