Robust Immune System Research Articles

Multiple diptericins of the black soldier fly (Hermetia illucens) differentially respond to bacterial challenges.

Due to its significant bioconversion potential, the black soldier fly (BSF), Hermetia illucens, shows great promise as a cost-effective alternative for recycling biological waste. BSF larvae (BSFL) are constantly exposed high levels of pathogenic microorganisms, including bacteria and fungi, which endows BSFL with a robust immune system. Diptericin, a type of glycine-rich antimicrobial peptide (AMP) that exhibits activity against gram-negative bacteria, contains proline-rich domains (P-domains) and glycine-rich domains (G-domains); these domains are separated by a furin cleavage site. Although the presence and expression patterns of BSFL diptericins have been documented, their basic molecular properties remain unclear. To the best of our knowledge, in the present study, we report, for the first time, the molecular characteristics of seven full-length cDNA sequences of H. illucens diptericins and their expression patterns following challenges with gram-positive or gram-negative bacteria. Seven diptericin paralogs are located in tandem on chromosome 2, spanning a total length of 38.6 kb, with an average intergenic distance of approximately 5.5 kb. Sequence analysis revealed that three diptericins (HipDptA/B/C) are pseudogenized due to premature stop codons. In contrast, the other diptericins (HiDpt1/2/3/4) possess mature-sized G-domains rich in glycine at the C-terminus, which are essential for AMP activity, along with proline-rich domain (P-domain) in the N-terminal and either two (HiDpt1/2/3) or one (HiDpt4) putative furin cleavage sites (R-X-R/K-R) between these domains. These furin cleavage sites possibly produce a glycine-rich AMP and one or two additional peptides with unknown functions. Similar to other diptericins, the expression of HiDpt1/2/3/4 mRNAs is predominantly induced by gram-negative bacteria, increasing typically by ≥ 1,000-fold (up to 5,000-fold). Additionally, HiDpt1/3/4 show significant responses to gram-positive bacteria such as Micrococcus luteus, though not as strongly as to gram-negative bacteria. These findings suggest that HiDpts function as a rapid, effective, and broad-spectrum first-line defense mechanism in the BSFL immune system.

Regulation of cell-mediated immune responses in dairy bulls via long non-coding RNAs from submandibular lymph nodes, peripheral blood, and the spleen

Cell-mediated immune responses (CMIRs) are critical to building a robust immune system and reducing disease susceptibility in cattle. Long non-coding RNAs (lncRNAs) regulate various biological processes. However, to the best of our knowledge, the characterization and functions of lncRNAs and their regulations on the bovine CMIR have not been investigated comprehensively. In this study, experimental bulls were immunized with a heat-killed preparation of Candida albicans (HKCA) to induce delayed-type hypersensitivity (DTH). Three bulls were classified as high- CMIR responders and three were low-CMIR responders, based on their classical DTH skin reactions. LncRNAs were identified in the submandibular lymph nodes, peripheral blood, and spleen of high- and low-CMIR animals using strand-specific RNA sequencing. A total of 21,003 putative lncRNAs were identified across tissues, and 420, 468, and 599 lncRNAs were differentially expressed between the two groups in the submandibular lymph node, peripheral blood, and spleen tissues, respectively. Functional analysis of the differentially expressed lncRNA (DElncRNA) target genes showed that a number of immune-related Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched, including immune response, cell adhesion, nucleosome, DNA packaging, antigen processing and presentation, and complement and coagulation cascades. Tissue specificity analysis indicated that lncRNA transcripts have stronger tissue specificity than mRNA. Furthermore, an interaction network was constructed based on DElncRNAs and DEGs, and 11, 14, and 11 promising lncRNAs were identified as potential candidate genes influencing immune response regulation in submandibular lymph nodes, peripheral blood, and spleen tissues, respectively. These results provide a foundation for further research into the biological functions of lncRNAs associated with bovine CMIR and identify candidate lncRNA markers for cell-mediated immune responses.

How Green Product and Green Promotion Factors to Consider in Purchasing Decision?

Preserving the environment and maintaining health are shared responsibilities. A robust immune system and overall good health are essential for everyone. Health is fundamental to carrying out daily life effectively. While a strong immune system is crucial, maintaining other bodily functions is equally important for optimal well-being. These efforts are crucial not only for enhancing quality of life but also for preventing global warming. Therefore, this study examines the influence of green products and green promotions on consumer purchase decisions. Employing a quantitative approach with an explanatory method, the research involved 224 Tropicana Slim consumers in Yogya Junction, Cirebon City, who had purchased the product at least once. Data were analyzed using the structural equation modeling (SEM) approach with the partial least squares (PLS) method. The findings indicate that green products and green promotions significantly impact consumer purchase decisions. As evidenced by the test results (t-value for Green Product > 6.722, p-value < 0.000; t-value for Green Promotion > 4.923, p-value < 0.000), both hypotheses are supported. This confirms that green products and green promotions positively influence purchasing decisions. We expect future research with a broader sample and more robust methodologies to strengthen these findings.

Under the radar: Transcriptomic responses of bed bugs to an entomopathogen, environmental bacteria, and a human pathogen

Bed bugs (Hemiptera: Cimicidae) are widely distributed, obligately blood-feeding insects, but they have never been linked to pathogen transmission in humans. Most other hematophagous insects that frequently bite humans transmit pathogens, and it is unclear why bed bugs do not. One hypothesis is that bed bugs have evolved a highly robust immune system because their mating system, traumatic insemination, exposes females to consistent wounding and bacterial infections. Although this has been proposed, very little is known about the bed bug immune system and how bed bugs respond to microbial challenges introduced by wounding. Similarly, there is little known about how the bed bug immune system responds to human pathogens. Understanding the bed bug immune system could give insight to why bed bugs appear not to transmit disease and under what circumstances they could, while also facilitating biological control efforts involving microbes. To investigate the transcriptomic response of bed bugs to immune challenges, we exposed female bed bugs to three bacterial challenges. 1.) Pseudomonas fluorescens, an entomopathogen known to have harmful effects to bed bugs, 2.) bacteria cultured from a bed bug enclosure (99.9 % Bacillus spp.), likely encountered during traumatic insemination, and 3.) Borrelia duttoni, a human vector-borne pathogen that causes relapsing fever. We compared the transcriptomes of infected bed bugs with uninfected matched controls in a pairwise fashion, focusing on immune-related genes. We found many known antimicrobial effector genes upregulated in response to P. fluorescens and traumatic insemination-associated bacteria, but interestingly, not in response to B. duttoni. In the differentially expressed genes that were shared between experiments, we found significant overlap in the P. fluorescens treatment and the traumatic insemination bacteria treatment, and between the P. fluorescens and B. duttoni treatments, but not between the traumatic insemination bacteria treatment and the B. duttoni treatment. Finally, we identify previously overlooked candidates for future studies of immune function in bed bugs, including a peroxidase-like gene, many putative cuticle-associated genes, a laccase-like gene, and a mucin-like gene. By taking a comprehensive transcriptomic approach, our study is an important step in understanding how bed bugs respond to diverse immune challenges.

The Significance of Prebiotics and Immuno-Nutrients for Assuring the Developmental Milestones in Toddlerhood

The immune system development of children is influenced by the mother's nutritional state throughout pregnancy as well as the nutrients the unborn kid is exposed to through nursing and other meals. Micronutrients that are important for the development of the immune system in neonates include iron, zinc, and vitamins A, C, D, and E. both probiotics and prebiotics are essential for maintaining a healthy gut microbiota and a robust immune system. While probiotics directly add beneficial bacteria to the gut, prebiotics serve as food for these bacteria, enhancing their growth and activity. Together, they play a vital role in supporting immune function and overall health. Prebiotics also play a significant role in this process by acting as fertilizers to encourage the growth of healthy bacteria in the stomach. Micronutrient deficiencies (MNDs) have an effect on the developing immune system; therefore, a meeting of specialists was arranged to talk about preventative and mitigating strategies. Immunological responses are largely determined by nutrition, and malnutrition is the leading cause of immunodeficiency worldwide. Protein-energy deprivation is associated with a significant decline in cell-mediated immunity, phagocyte activity, complement system, secretory immunoglobulin an antibody concentration, and cytokine production. Certain nutrient deficits cause altered immune responses, even in cases when the deficiency is fairly mild. The immune responses are significantly influenced by micronutrients such as folic acid, zinc, selenium, iron, copper, and vitamins A, C, E, and B-6. Additionally, overeating and obesity reduce immunity. Low birth weight babies' cell-mediated immunity is permanently compromised; this can be somewhat restored by adding more zinc to their diets. Prebiotics are inactive dietary ingredients that, when combined with immuno-nutrients, benefit the host by encouraging the growth and/or activity of a certain kind of bacteria in the colon. Government, development partners, non-governmental organizations, and academia must collaborate to increase the availability of basic and effective nutrition interventions, as well as those that address more stifling issues. These interventions include exclusive breastfeeding, appropriate supplemental feeding, micronutrient supplementation for children, adolescents, pregnant women, and lactating women, managing severe acute malnutrition and deworming, and hygiene interventions. The entire healthcare system needs to be revitalized in order to get over the obstacles that exist at the levels of policy, governance, and service delivery and to create demand for the services at the household level. Priority should also be devoted to stabilizing food prices and managing nutrition following natural disasters.

Adverse effects of cadmium on lymphoid organs, immune cells, and immunological responses.

Humans and animals possess robust immune systems to safeguard against foreign pathogens. However, recent reports suggest a greater incidence of immunity breakdown due to exposure to environmental pollutants, with heavy metals emerging as potential candidates in such immuno-toxicological studies. While we have extensive data on the general toxicity resulting from exposure to heavy metals, comprehensive documentation of their role as immune disruptors remains scarce. Cd (Cadmium) exerts immunomodulation by interfering with immune organs and cells, leading to altered structure, physiology, and function, thereby inducing symptoms of immune deregulation, inflammation and/or autoimmunity. This review aims to summarize the link between Cd exposure and immune dysfunction, drawing from case studies on exposed human subjects, as well as research conducted on various model organisms and in-vitro culture systems.

Alternative splicing of a potato disease resistance gene maintains homeostasis between growth and immunity.

Plants possess a robust and sophisticated innate immune system against pathogens and must balance growth with rapid pathogen detection and defense. The intracellular receptors with nucleotide-binding leucine-rich repeat (NLR) motifs recognize pathogen-derived effector proteins and thereby trigger the immune response. The expression of genes encoding NLR receptors is precisely controlled in multifaceted ways. The alternative splicing (AS) of introns in response to infection is recurrently observed but poorly understood. Here we report that the potato (Solanum tuberosum) NLR gene RB undergoes AS of its intron, resulting in 2 transcriptional isoforms, which coordinately regulate plant immunity and growth homeostasis. During normal growth, RB predominantly exists as an intron-retained isoform RB_IR, encoding a truncated protein containing only the N-terminus of the NLR. Upon late blight infection, the pathogen induces intron splicing of RB, increasing the abundance of RB_CDS, which encodes a full-length and active R protein. By deploying the RB splicing isoforms fused with a luciferase reporter system, we identified IPI-O1 (also known as Avrblb1), the RB cognate effector, as a facilitator of RB AS. IPI-O1 directly interacts with potato splicing factor StCWC15, resulting in altered localization of StCWC15 from the nucleoplasm to the nucleolus and nuclear speckles. Mutations in IPI-O1 that eliminate StCWC15 binding also disrupt StCWC15 re-localization and RB intron splicing. Thus, our study reveals that StCWC15 serves as a surveillance facilitator that senses the pathogen-secreted effector and regulates the trade-off between RB-mediated plant immunity and growth, expanding our understanding of molecular plant-microbe interactions.

The CD40/CD40L dyad, an immune checkpoint regulator, plays a protective role against Mouse hepatitis virus-induced neuroinflammatory demyelination

Abstract Murine ꞵ-coronavirus, RSA59, infection results in meningoencephalitis, demyelination, and axonal loss. CD40-CD40L dyad serves as an important immune checkpoint regulator during this disease pathobiology. C57BL/6 WT, CD4-/-, CD40L-/- and CD40-/- mice were intracranially inoculated with RSA59 to study the acute phase neuroinflammation and chronic phase demyelination. Studies suggested that CD4+ T cells play a protective role against RSA59-induced demyelination because, in the absence of CD4 gene, mice were more susceptible to acute poliomyelitis and chronic demyelination with axonal bulbar vacuolation. CD40L expressed by CD4+ T cells is crucial for host immunity against RSA59. Without CD40L in activated CD4+ T cells, RSA59-infected mice experience increased disease severity, dampened microglia/macrophage activation, reduced T cell infiltration in the CNS, and impaired T cell priming in the cervical lymph node. In the chronic phase, extensive CNS virus replication leads to severe demyelination and axonopathy due to altered microglia/macrophage populations caused by the absence of the CD40L gene. CD40-deficiency revealed increased acute phase encephalitis in the RSA59-infected groups due to increased infiltrating neutrophils, leading to heightened bystander neuroinflammation. Hence, it is evident that the RSA59-induced demyelination model elucidates an extensively robust innate immune system upon which adaptive immunity is built during the chronic stage of infection.

Intramammary lipopolysaccharide challenge in early- versus mid-lactation dairy cattle: Immune, production, and metabolic responses

Study objectives were to compare the immune response, metabolism and production following intramammary lipopolysaccharide (IMM LPS) administration in early and mid-lactation cows. Early (E-LPS; n = 11; 20 ± 4 d in milk [DIM]) and mid- (M-LPS; n = 10; 155 ± 40 DIM) lactation cows were enrolled in an experiment consisting of 2 periods (P). During P1 (5 d) cows were fed ad libitum and baseline data were collected, including liver and muscle biopsies. At the beginning of P2 (3 d) cows received 10 mL sterile saline containing 10 µg of LPS from Escherichia coli O111:B4/mL into the left rear quarter of the mammary gland, and liver and muscle biopsies were collected at 12 h post-LPS. Tissues were analyzed for metabolic flexibility, which measures substrate switching capacity from pyruvic acid to palmitic acid oxidation. Data were analyzed with the MIXED procedure in SAS 9.4. Rectal temperature was assessed hourly for the first 12 h post-LPS and every 6 h thereafter for the remainder of P2. All cows developed a febrile response following LPS, but E-LPS had a more intense fever than M-LPS cows (0.7°C at 5 h after LPS). Blood samples were collected at 0, 3, 6, 9, 12, 24, 36, 48, and 72 h post-LPS for analysis of systemic inflammation and metabolism parameters. Total serum Ca decreased after LPS (26% at 6 h nadir) but did not differ by lactation stage (LS). Circulating neutrophils decreased, then increased post-LPS in both LS, but E-LPS had exaggerated neutrophilia (56% from 12 to 48 h) compared with M-LPS. Haptoglobin increased after LPS (15-fold) but did not differ by LS. Many circulating cytokines were increased post-LPS, and IL-6, IL-10, TNF-α, MCP-1, and IP-10 were further augmented in E-LPS compared with M-LPS cows. Relative to P1, all cows had reduced milk yield (26%) and dry matter intake (DMI; 14%) on d 1 that did not differ by lactation stage (LS). Somatic cell score increased rapidly in response to LPS regardless of LS and gradually decreased from 18 h onwards. Milk component yields decreased after LPS. However, E-LPS had increased fat (11%) and tended to have increased lactose (8%) yield compared with M-LPS cows throughout P2. Circulating glucose was not affected by LPS. Nonesterified fatty acids (NEFA) decreased in E-LPS (29%) but not M-LPS cows. β-hydroxybutyrate (BHB) slightly increased (14%) over time post-LPS regardless of LS. Insulin increased after LPS in all cows, but E-LPS had blunted hyperinsulinemia (52%) compared with M-LPS cows. Blood urea nitrogen (BUN) increased after LPS and the relative change in BUN was elevated in E-LPS cows compared with M-LPS cows (36 and 13%, respectively, from 9 to 24 h). During P1, metabolic flexibility was increased in liver and muscle in early lactating cows compared with mid-lactation cows, but 12 h post-LPS, metabolic flexibility was reduced and did not differ by LS. In conclusion, IMM LPS caused severe immune activation and E-LPS cows had a more intense inflammatory response compared with M-LPS cows, but the effects on milk synthesis was similar between LS. Some parameters of the E-LPS metabolic profile suggest continuation of metabolic adjustments associated with early lactation to support both a robust immune system and milk synthesis.

Pediatric corneal transplantation: techniques, challenges, and outcomes.

Pediatric corneal transplant is a highly demanding and technically challenging procedure for the cornea surgeon in today's era. These cases pose unique challenges in clinical and surgical management. The indications of pediatric corneal transplant can be therapeutic, tectonic, optical, and cosmetic. Pediatric patients undergoing corneal transplants are at a high risk of graft infection, failure, rejection, dehiscence, and amblyopia due to young age, robust immune system, increased incidence of trauma, and compliance issues. The other factors contributing to graft failure can be allograft rejection, secondary glaucoma, corneal vascularization, multiple surgeries, vitreous prolapse, and lack of treatment compliance. A successful corneal transplant in children depends on meticulous preoperative evaluation, uneventful surgery, the expertise of a corneal surgeon, and regular and timely postoperative follow-up. Therapeutic and optical penetrating keratoplasty are the most commonly performed transplants in children. However, with the advancements in surgical technique and management protocol, the current focus has shifted toward lamellar keratoplasty. Lamellar keratoplasty offers early visual recovery and potentially fewer complications. Visual rehabilitation through corneal transplant in otherwise blind eyes can be a boon for the children. Recently, keratoprostheses have been promising in children with multiple graft failures. The current review gives insights into epidemiology, etiology, indications, clinical characteristics, investigations, management options, recent advances, and the future of pediatric corneal transplants. As surgical techniques continue to grow and comprehension of pediatric corneal transplants is improving, we can safeguard these eyes with the best possible anatomical and functional outcomes.

Paving new roads toward the advancement of broad-spectrum antiviral agents.

Broad-spectrum antivirals (BSAs) have the advantageous property of being effective against a wide range of viruses with a single drug, offering a promising therapeutic solution for the largely unmet need in treating both existing and emerging viral infections. In this review, we summarize the current strategies for the development of novel BSAs, focusing on either targeting the commonalities during the replication of multiple viruses or the systemic immunity of humans. In comparison to BSAs that target viral replication, these immuno-modulatory agents possess an expanded spectrum of antiviral activity. However, antiviral immunity is a double-edged sword, and maintaining immune homeostasis ultimately dictates the health status of hosts during viral infections. Therefore, establishing an ideal goal for immuno-modulation in antiviral interventions is crucial. Herein we propose a bionic approach for immuno-modulation inspired by mimicking bats, which possess a more robust immune system for combating viral invasions, compared to humans. In addition, we discuss an empirical approach to treat diverse viral infections using traditional Chinese medicines (TCMs), mainly through bidirectional immuno-modulation to restore the disrupted homeostasis. Advancing our understanding of both the immune system of bats and the mechanisms underlying antiviral TCMs will significantly contribute to the future development of novel BSAs.

A Study on Knowledge on Antenatal Care among Mothers Admitted in Obstetric Ward in Dhaka Medical College and Hospital

Introduction: Adequate prenatal treatment is crucial to supporting optimal fetal development, appropriate organogenesis, and a robust immune system in the infant. The nutritional status of the mother has a direct effect on both her own health and the health of her child. Methodology: This was a cross-sectional study conducted at the Obstetric Ward in Dhaka Medical College and Hospital from January 2019 to April 2019, and a total of 150 admitted mothers from the Obstetric Ward enrolled in this study. The data was collected using a pretested, modified questionnaire. The data was inputted and analyzed using the Statistical Package of Social Science (SPSS) software, specifically version 23.0. The study gained ethical clearance from the Institutional Review Board (IRB) of Dhaka Medical College and Hospital in Dhaka, Bangladesh. Objective: The study aimed to assess the knowledge of antenatal care among mothers admitted to the obstetric ward at Dhaka Medical College and Hospital. Results: According to age distribution, 50%, 41.3%, and 8.7% of the respondents belonged to the age groups of 15–25 years, 26–35 years, and 36–45 years, respectively, with a mean age of 26.47 ± 5.652 years. According to the distribution by family type, the majority of the respondents (66%) belonged to the nuclear family and only 34% were in the joint family. The study revealed that the majority of the respondents (25.3%) education was primary, followed by 20% being SSC, 34.7% being HSC, 7.3% being graduates and only 12.7% being illiterate. According to the distribution by profession, 71.3 percent of respondents were housewives and the rest of them, 28.7%, were in service. According to the distribution by residence, most of the respondents (48.7%) were from finished buildings, 10.7% were from semi-pucca buildings and only 40.7% were from other types of residence. Most respondents (73.3%) used sanitary toilets and only 26.7% used non-sanitary toilets. Most of the respondents (82%) were Muslims, 9.3% were Hindus, 4.7% were Christians, 2.7% were Buddhists, and only 1.3% had other religions. Among the respondents, (32.7%) had antenatal clinics available in their community and 67.3% had no antenatal clinics in their community. The majority of the respondents (66%) received antenatal care during pregnancy and 34% did not receive any antenatal care during pregnancy. Most of the respondents (86%) knew that vaccination was important during pregnancy and 14% had no knowledge of the importance of vaccination during pregnancy. Among the respondents, (48.7%) had knowledge of four ANC visits and 51.3% had two visits. The majority of the respondents (82.7%) had a normal mode of delivery and 17.3% had a cesarean section. The majority of the respondents (86.7%) received ANC in the clinic and 13.3% at home. Most of the respondents (88.7%) were more than 18 years old while getting married and 11.3% were less than 18 years old. Most of the respondents (90%) were 20 years old at the birth of their first baby, while 10% were less than 20 years old. The majority of the respondents (61.3%) babies’ birth weight was more than 2.5 kg at birth and 38.7% of respondents’ babies' birth weight was less than 2.5 kg at birth. The majority of the respondents (85.3%) got information from an NGO or hospital, 66% from TV, 0.7% from radio, 1.3% from print media, 6% from billboards, and 21.3% from family physicians. Finally, this study revealed a statistically significant association between the respondent’s knowledge about the toxemia of pregnancy and the age of the respondents (P = 0.001), as well as a highly significant association between the respondent’s sex and the written protocol for universal precaution. (P=0.000). Conclusion: This study revealed that the level of knowledge of the participants regarding antenatal care was moderate. To improve this situation, there is an urgent need for multi-channel awareness.

A Concise Review: Nutritional Interventions for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

Wuhan, China reported a novel coronavirus-related sickness in late 2019, which quickly spread into a global epidemic. One crucial factor in combating the coronavirus infection appears to be the presence of a robust, long-lasting, and active immune system. The immune response is affected by several factors, including food. Nutritional insufficiency can cause immune deficits, making infections more likely to cause fatality. Thus, understanding numerous behaviors, particularly dietary habits, is essential to determining their capacity to reduce severe acute respiratory syndrome coronavirus 2 risks and improve prognosis. In this paper, the authors summarize the complex interaction between nutritional status and severe acute respiratory syndrome corona virus 2 infections, as well as the consequences of poor nutrients with regard of the extent to which disease is affected. The literature was compiled by searching a number of reputable scientific databases including Scopus, Science Direct, Springer, Nature, PubMed, Web of Science resources. The accumulating evidence demonstrates that malnutrition impairs the immune system's ability to function, weakening the body's infection resistance. This review emphasizes the significance of nutritional status in the care of coronavirus disease patients as well as demonstrates that functional foods may contribute to better outcomes. Ageing, Obesity, Malnutrition, Undernutrition, Lack of exercise are having a devastating effect on people's health in general and during this coronavirus disease. The severity and prognosis of coronavirus illness seem to be significantly influenced by lifestyle choices, nutritional imbalances, and impaired immune response.

A Critical Review on the Role of Camel Milk in Multiple Health Outcomes

Camel milk has been demonstrated to be effective in treating a broad range of illnesses. Camel’s milk is regarded to have therapeutic properties because of its unique composition. Some people consider camel milk to be a precious commodity. White camel milk is made by combining fat and water. Several clinical studies have shown that camel’s milk is effective in treating a broad variety of diseases, including chronic ones. Most of the medicinal advantages of camel milk are included in this study. Camel Milk ingredients and qualities are similar to those found in mother’s milk, making it superior than cow’s milk. Insulin-like and protective proteins are found in abundance, along with lactose, which is the primary carbohydrate. It has anti-tumor qualities, and the robust immune system components assist combat disorders, including diabetes, autism, and diarrhea. It has been used by Nomads and Bedouins (Arabian tribals) for millennia because of these properties. The main objective of this review article is to demonstrate its various pharmacological roles. Camel’s milk is regarded as a vast medicinal property, as it contains a unique composition of bioactive moieties like lactose, proteins (Lactoferrin, Lactoperoxidase, Insulin, Casein), vitamins (A, B1, B2, C, D, E), minerals (Calcium, phosphorus, magnesium, iron, zinc and copper) carbohydrates etc. Most of the medicinal advantages of camel milk are covered in this paper, like its role in the management of autism, Crohn’s disease, allergic conditions, Hepatitis B and C, as antiviral and antibacterial agent. Hence, this study was planned to collect the updated latest information regarding use of camel’s milk, which will be very beneficial in the field of medicines and managing various ailments for the benefit of mankind.

290 Vitamin A and Beta-Carotene Supplementation on Growth Performance, Immune System, and Mammary Gland Development in Finishing Pigs

Abstract A total of 224 finishing pigs were randomly assigned to split-sex pens (n = 4 pigs per pen). Each pen was assigned to one of four diets: control (7,656 IU vitamin A/kg), control diet supplemented with vitamin A (4.36 ppm; Rovimix A 1000, DSM, NJ, US), control diet supplemented with beta-carotene (163.28 ppm; Rovimix β-Carotene 10%, DSM, NJ, US), or control supplemented with oxidized beta-carotene (40 ppm; 10% active ingredient, Avivagen, Ottawa, ON, Canada). Pigs and feeder weights were recorded at the start of the study (d 0) and end of each phase (days 21, 42, and 63). A subset of gilts was randomly selected and a blood sample for vitamin A (retinol) analysis was collected on days 0, 18, 39, 60, and 63. The same gilts were vaccinated against Lawsonia intracellularis and porcine circovirus. Antibodies against each vaccination were measured on days 18, 39, and 60. At the end of the study, the subset of gilts was euthanized to obtain a liver sample for vitamin A (retinyl palmitate is converted to retinol for measurement) analysis and a jejunum sample to measure the mRNA abundance of genes involved in vitamin A metabolism (alcohol dehydrogenase class 1, lecithin retinol acyltransferase phosphatidylcholine-retinol O-acyltransferase, retinol binding protein, and beta-carotene oxygenase 1). Mammary tissue from the second and fourth right anterior mammary glands were collected to assess gland development via immunohistochemical staining for T cells, B cells, and macrophages (CD3, CD20, and IBA1, respectively) and DNA extraction. Vaccine antibodies measures, vitamin A analysis, and mammary immunohistochemical staining was completed at Iowa State University Veterinarian Diagnostic Laboratory (Ames, IA). Data were analyzed in SAS 9.4 (Statistical Analysis System, Cary, NC) via GLIMMIX procedure. Pen was the experimental unit and fixed effects were diet and time. Gilts were nested within pen when appropriate to account for more than one gilt per pen. Oxidized beta-carotene supplementation increased (P = 0.02) average daily gain across phases; however, there were no differences (P = 0.18) in the body weight of pigs. There was no effect (P > 0.05) of diet on plasma or hepatic retinol, IgG or IgM concentrations, immune cell presence, or DNA in mammary tissue. Supplemented vitamin A tended (P = 0.05) to increase the expression of retinol binding protein in the jejunum, but other genes were not affected (P > 0.05) by dietary treatments. A diet by time interaction (P = 0.04) was noted for circovirus sample-to-positive ratios and titer levels, where vitamin A supplementation had better vaccine responses at the end of the study. Thus, pigs supplemented with oxidized beta-carotene had an improved average daily gain over vitamin A supplemented pigs, but pigs supplemented with vitamin A appeared to have a more robust immune system.

Cakes fortified with papaya seeds effectively protects against CCl4-induced immunotoxicity

Maintaining a robust immune system and safeguarding the liver from toxins are crucial for overall health. The study aimed to investigate the immunostimulant effects of papaya seed-enriched cakes (CPS) in countering carbon tetrachloride (CCl4)-induced immunocytotoxicity in rats (n = 48). The rats were divided into six groups (8 each): a control group (Group 1), rats fed cakes containing 15% papaya seeds (Group 2 — CPS), rats exposed only to CCl4 (Group 3 — CCl4), rats injected with CCl4 and administered silymarin (Group 4 — CCl4 + S), rats receiving both CCl4 and cakes with papaya seeds (Group 5 — CCl4 + CPS), and rats receiving both CCl4 and silymarin with papaya seed-enriched cakes (Group 6 — CCl4 + CPS + S). HPLC analysis of papaya seeds revealed the presence of ten polyphenol compounds, with quercetin, apigenin, and catechin identified as major flavonoids, along with pyrogallol, ellagic, and gallic acid as predominant phenolic acids. These compounds displayed potent antioxidant activity, attributed to the seeds’ high total phenolic and flavonoid content. The administration of CCl4 significantly affected hematological parameters, liver enzymes, hepatic oxidative stress, levels of TNF-α, IL-6, IgG, as well as IgM. However, rats fed with CPS exhibited mitigation of CCl4-induced toxic effects on hematological parameters and hepatotoxicity. CPS consumption enhanced the antioxidant system, improved inflammatory markers, and immune parameters, restoring them to normal levels. Histopathological analysis confirmed CPS’s ability to reduce CCl4-induced hepatocellular necrosis. Immunohistochemical assessment further revealed reduced immunoreactivity against cleaved caspase-3 expression and increased COX2 immunoreactivity, indicating hepatocellular regeneration in CPS. The combination of CPS and silymarin demonstrated even more notable improvements, suggesting augmented protective impacts against CCl4-induced immunosuppression and hepatotoxicity. In conclusion, CPS exhibited antioxidant properties and effectively protected against CCl4-induced immunotoxicity and hepatotoxicity, with additional benefits observed when combined with silymarin. These findings emphasize the potential health advantages of incorporating papaya seeds into food products, promoting immune system health, and safeguarding against liver damage induced by hazardous agents like CCl4.

Impact of Lymphopenia on Definitive Treatment of Locally Advanced Cervical Cancer

Pre-treatment lymphopenia prior to initiating treatment has been correlated with reduced survival in a number of different cancers. The purpose of this study is to evaluate the association between lymphopenia and survival in women with locally advanced cervical cancer (LACC) treated with primary chemoradiation (CRT). We retrospectively reviewed patients with LACC treated at a single institution from 2005 - 2021 with available lymphocyte information. Patient and treatment characteristics were recorded including age, tumor size and stage, EBRT dose/fractionation, and brachytherapy dosimetry data. Absolute lymphocyte counts (ALC) were collected prior to initiating CRT and at 3-month intervals following CRT and graded based on severity of lymphopenia using CTCAE v 5.0. Overall survival (OS), progression free survival (PFS), and local control (LC) were calculated from the start of treatment to date of last follow-up. Kaplan-Meier survival analysis was performed to evaluate whether lymphocyte changes were associated with OS, PFS, or LC. A total of 124 patients met study inclusion criteria with stage IB - IV disease (41 stage I, 41 stage II, 36 stage III, 6 stage IV) and a median follow up of 3.6 years (range 0.2-16.5 years). The median age was 49 years (range 26-77). The median EBRT dose was 45 Gy (range: 26-57.5 Gy) and 44.2% of patients received para-aortic (PA) nodal EBRT (28.8% elective and 15.4% with positive PA nodes). 5-year OS, PFS, and LC were 60.3% (95% CI 51.5-70.7), 47.5% (95% CI 39-58), and 75.5% (95% CI 67.3-82.9), respectively. Pre-treatment lymphopenia (ALC <1000 cells/mm3) was present in 11 (9%) patients. When the total cohort was divided into patients with and without pre-treatment lymphopenia, OS was statistically improved in the patients without baseline lymphopenia, with a 5-year OS of 63.2% (95% CI 53.9-73.9) versus 35.3% (95% CI 14.5-86.3) in the lymphopenia group (p = 0.034). LC also trended to being improved in the patients without lymphopenia, though this did not reach statistical significance in our small sample size of lymphopenic patients, with 5-year LC of 76.8% (95% CI 68.4-84.3) versus 67.5% (05% CI 36.6-93.8), p = 0.45. In this single institution experience of LACC treated with definitive CRT, we found that baseline lymphopenia is associated with inferior OS. Patients with higher pre-CRT ALC may represent a population with more robust immune systems, producing more favorable tumor responses to treatment. Additional studies are warranted to investigate the evolving role of combined EBRT and systemic therapy in LACC.

GraS signaling in Staphylococcus aureus is regulated by a single D35 residue in the extracellular loop.

Bacterial two-component systems are crucial features of bacterial pathogens such as methicillin-resistant Staphylococcus aureus to overcome environmental and antimicrobial stresses by activating regulons to interfere with the bactericidal mechanisms. GraRS is a unique subset of two-component systems belonging to the intramembrane-sensing histidine kinase family (IM-HK) and is responsible for resistance to cationic host defense peptides. However, the precise manner by which the short 9-residue extracellular loop of the membrane sensor GraS detects the antimicrobial peptides and transduces the signal is not comprehensively understood. Here, we show that a single point mutation (D35A) in the extracellular loop of GraS blocked activation of GraRS, but this effect was also abrogated with graS mutations in the N-terminal transmembrane segments without any accompanying effect on GraS protein expression. Additionally, mutations in H120 and T172 in the dimerization/histidine phosphotransfer (DHp) domain of GraS increased activation without any accompanying enhancement in dimerization, likely due to disruption of the H120-T172 interaction that restricts rotational movements of the DHp helices since swapping H120 and T172 did not alter GraS activation. Notably, the enhancing effects of H120 and T172 mutations were abolished with a D35 mutation, highlighting the pivotal role of D35 in the 9-residue extracellular loop of GraS in GraR phosphorylation. In summary, our study delivers the significance of the D35 in the extracellular loop of GraS and ensuing changes in the N-terminal transmembrane helices as a model to illustrate signaling in the IM-HK subset of two-component regulatory systems. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is a human pathogen capable of infecting skin, blood, internal organs, and artificial medical devices. Generally, personal hygiene and a robust immune system can limit the spread of this pathogen; however, MRSA possesses an assortment of phenotypic tools to survive the hostile host environment including host defense peptides. More specifically, S. aureus utilizes two-component systems to sense noxious environmental cues to respond to harmful environmental elements. Our study focused on a two-component system called GraRS that S. aureus deploys against host defense peptides. We showed that one single residue in the extracellular loop of GraS and the adjacent membrane segment controlled the activation of GraRS, indicating the importance of a well-tuned-charged residue in the extracellular loop of GraS for sensing activity.

Long-Read Sequencing Reveals Rapid Evolution of Immunity- and Cancer-Related Genes in Bats.

Bats are exceptional among mammals for their powered flight, extended lifespans, and robust immune systems and therefore have been of particular interest in comparative genomics. Using the Oxford Nanopore Technologies long-read platform, we sequenced the genomes of two bat species with key phylogenetic positions, the Jamaican fruit bat (Artibeus jamaicensis) and the Mesoamerican mustached bat (Pteronotus mesoamericanus), and carried out a comprehensive comparative genomic analysis with a diverse collection of bats and other mammals. The high-quality, long-read genome assemblies revealed a contraction of interferon (IFN)-α at the immunity-related type I IFN locus in bats, resulting in a shift in relative IFN-ω and IFN-α copy numbers. Contradicting previous hypotheses of constitutive expression of IFN-α being a feature of the bat immune system, three bat species lost all IFN-α genes. This shift to IFN-ω could contribute to the increased viral tolerance that has made bats a common reservoir for viruses that can be transmitted to humans. Antiviral genes stimulated by type I IFNs also showed evidence of rapid evolution, including a lineage-specific duplication of IFN-induced transmembrane genes and positive selection in IFIT2. In addition, 33 tumor suppressors and 6 DNA-repair genes showed signs of positive selection, perhaps contributing to increased longevity and reduced cancer rates in bats. The robust immune systems of bats rely on both bat-wide and lineage-specific evolution in the immune gene repertoire, suggesting diverse immune strategies. Our study provides new genomic resources for bats and sheds new light on the extraordinary molecular evolution in this critically important group of mammals.

Immunomodulatory, cyto-genotoxic, and growth regulatory effects of nerolidol on melon fruit fly, Zeugodacus cucurbitae (Coquillett) (Diptera: Tephritidae)

Insects have evolved a robust immune system consisting of humoral and cellular branches and their orchestrated response enables insect to defend against exogenous stressors. Exploration of underlying immune mechanisms of insect pest under allelochemical stress can give us new insights on insect pest management. In this study, nerolidol, a plant sesquiterpene was evaluated for its insecticidal, growth regulatory, immunomodulatory, and cyto-genotoxic effects against melon fruit fly, Zeugodacus cucurbitae (Coquillett). First, second, and third instar larvae of Z. cucurbitae were fed on artificial diet containing different concentrations (5, 25, 125, 625, and 3125 ppm) of nerolidol. Results revealed a significant reduction in pupation and adult emergence as well as prolongation of developmental duration of treated larvae. Decline in growth indices showed remarkable growth inhibitory effects of nerolidol. Pupal weight and nutritional parameters viz. Larval weight gain, food assimilated, and mean relative growth rate declined after treatment. Immunological studies on second instar larvae depicted a drop in total hemocyte count and variations in proportions of plasmatocytes and granulocytes of LC30 and LC50 treated larvae. Phenoloxidase activity in nerolidol treated larvae initially increased but was suppressed after 72 h of treatment. The frequency of viable hemocytes decreased and that of apoptotic and necrotic hemocytes increased with both the lethal concentrations of nerolidol. Comet assay revealed a significant damage to DNA of hemocytes. The findings of the current study indicate that nerolidol exerts its insecticidal action through growth regulation, immunomodulation, and cyto-genotoxicity thus revealing its potential to be used as biopesticide against Z. cucurbitae.