Gold nanoparticles (GNPs) are biocompatible nanomaterials that are currently researched for biomedical applications such as imaging and targeted drug delivery. In this investigation, we studied the effects of a single dose (injected on day 1) as well as a priming dose (two injections with a gap of one week) of 5 nm, 20 nm, and 50 nm diameter GNPs on the structural and biochemical changes in the liver, kidney, and spleen of mice. The results showed that small sized GNPs (5 nm) produced significant pathological changes in the liver on day 2 that gradually reduced on day 8. The medium (20 nm) and large (50 nm) sized GNPs preferentially targeted the spleen and caused significant pathological changes to the spleen architecture on day 2 that persisted on day 8 as well. There were minimal and insignificant pathological changes to the kidneys irrespective of the GNPs size. The animals that were primed with the pre-exposure of GNPs did not show any aggravation of histological changes after the second dose of the same GNPs. None of the dose regimens of the GNPs were able to significantly affect the markers of oxidative stress including glutathione (GSH) and malondialdehyde (MDA) in all of the organs that were studied. In conclusion, the size of GNPs plays an important role in their pathological effects on different organs of mice. Moreover, the primed animals become refractory to further pathological changes after the second dose of GNPs, suggesting the importance of a priming dose in medical applications of GNPs.

Gum Arabic (GA) belongs to the Fabaceae family and contains indigestible soluble fibers (80–85%) that could be fermented by commensal bacteria to enhance performance, immune response, and intestinal integrity. This study aimed to investigate the effects of GA on performance, serum biochemical indicators, microbiota, immune-related gene expression, and histological changes in chickens. Six GA levels (0.0, 0.12, 0.25, 0.5, 0.75, 1.0%) were allocated using a total of 432 1-day-old male chickens (12 replicates with 6 chickens each). Growth performance was evaluated on days 10 and 24 of age. Blood parameters, organ pH levels, and intestinal health were determined on day 10 of age. Results showed that GA at 0.12% increased weight gain and 0.12 to 1.0% decreased feed intake but was best in feed conversion ratio and production efficiency except for 1.0% on day 1–10 of age. There was an increase in the thymus weight at GA level 0.25 to 0.75%. GA decreased the pH value of the proventriculus (at 0.50 and 1.0%) as well as the duodenum and cecum (at 0.12 and 1.0%). Chickens fed GA between 0.25 to 1.0% had higher protein and HDL, but lower cholesterol, LDL, and creatinine. Globulin was increased at 0.50% GA, while glucose and triglycerides were decreased (at 0.25 and 0.75% GA, respectively). The immune-related gene expression was reduced, except for 0.25% GA, which increased IL-10. Furthermore, chickens fed GA (0.25 to 0.75%) had higher Lactobacillus spp. and lower Salmonella spp. and Escherichia coli. When chickens received GA, the villus length and length to crypt ratio were higher, which also improved the integrity of intestinal epithelial cells and early duodenal development. We conclude that using GA (0.25 to 0.75%) as a natural prebiotic positively affects the performance, microbiota, immune response, morphology, and gut health of post-hatched chickens. More studies are needed to determine the potential mechanism of GA on broiler chickens.

Asthma is one of the most common inflammatory diseases affecting the airways. Approximately 300 million individuals suffer from asthma around the world. Allergic immune responses in the asthmatic airways are predominantly driven by Th2 cells and eosinophils. Lymphocyte-specific protein tyrosine kinase (LCK) is a non-receptor tyrosine kinase which regulates several key intracellular events through phosphorylation of its substrates. Some of the intracellular signaling pathways activated by LCK phosphorylation help in differentiation of Th2 cells which secrete allergic cytokines that amplify airway inflammation. Therefore, this investigative study was designed to determine the role of LCK in a cockroach extract (CE)-induced airway inflammation murine model of allergic asthma. Further, the effect of a pharmacological LCK inhibitor, A-770041, on allergic airway inflammation and key intracellular pathways in CD4+ T cells was assessed. Our data exhibit that there is an activation of LCK during allergic airway inflammation as depicted by increased p-LCK levels in CD4+ T cells. Activated LCK is involved in the activation of ITK, PLC-γ, GATA3, NFkB, and NFATc1. Activated LCK is also involved in the upregulation of Th2 related cytokines, such as IL-4/IL-5/IL-13 and oxidative stress, and the downregulation of Treg cells. Furthermore, utilization of LCK inhibitor causes the reduction in p-LCK, PLC-γ, GATA3, and NFATc1 as well as Th2 cytokines and oxidative stress. LCK inhibitor causes upregulation of Treg cells in allergic mice. LCK inhibitor also caused a reduction in CE-induced airway inflammation and mucus secretion. Therefore, the inhibition of LCK signaling could be a fruitful approach to adjust allergic airway inflammation through the attuning of Th2/Treg immune responses. This study could lead to the design of newer treatment options for better management of allergic inflammation in asthma.

In this study, for the first time, boron oxide nanoflake is analyzed as drug carrier for favipiravir using computational studies. The thermodynamic stability of the boron oxide and favipiravir justifies the strong interaction between both species. Four orientations are investigated for the interaction between the favipiravir and the B₃O₃ nanoflake. The E_int of the most stable orientation is −26.98 kcal/mol, whereas the counterpoise-corrected energy is −22.59 kcal/mol. Noncovalent interaction index (NCI) and quantum theory of atoms in molecules (QTAIM) analyses are performed to obtain insights about the behavior and the types of interactions that occur between B₃O₃ nanoflake and favipiravir. The results indicate the presence of hydrogen bonding between the hydrogen in the favipiravir and the oxygen in the B₃O₃ nanoflake in the most stable complex (FAV@B₃O₃-C1). The electronic properties are investigated through frontier molecular orbital analysis, dipole moments and chemical reactivity descriptors. These parameters showed the significant activity of B₃O₃ for favipiravir. NBO charge analysis transfer illustrated the charge transfer between the two species, and UV-VIS analysis confirmed the electronic excitation. Our work suggested a suitable drug carrier system for the antiviral drug favipiravir, which can be considered by the experimentalist for better drug delivery systems.

Sepsis affects millions of people worldwide and is associated with multiorgan dysfunction that is a major cause of increased morbidity and mortality. Sepsis is associated with several morbidities, such as lung, liver, and central nervous system (CNS) dysfunction. Sepsis-associated CNS dysfunction usually leads to several mental problems including depression. IL-17A is one of the crucial cytokines that is expressed and secreted by Th17 cells. Th17 cells are reported to be involved in the pathogenesis of depression and anxiety in humans and animals. One of the protein tyrosine kinases that plays a key role in controlling the development/differentiation of Th17 cells is ITK. However, the role of ITK in sepsis-associated neuroinflammation and depression-like symptoms in mice has not been investigated earlier. Therefore, this study investigated the efficacy of the ITK inhibitor, BMS 509744, in sepsis-linked neuroinflammation (ITK, IL-17A, NFkB, iNOS, MPO, lipid peroxides, IL-6, MCP-1, IL-17A) and a battery of depression-like behavioral tests, such as sucrose preference, tail suspension, and the marble burying test. Further, the effect of the ITK inhibitor on anti-inflammatory signaling (Foxp3, IL-10, Nrf2, HO-1, SOD-2) was assessed in the CNS. Our data show that sepsis causes increased ITK protein expression, IL-17A signaling, and neuroinflammatory mediators in the CNS that are associated with a depression-like state in mice. ITK inhibitor-treated mice with sepsis show attenuated IL-17A signaling, which is associated with the upregulation of IL-10/Nrf2 signaling and the amelioration of depression-like symptoms in mice. Our data show, for the first time, that the ITK inhibition strategy may counteract sepsis-mediated depression through a reduction in IL-17A signaling in the CNS.

Diabetes Mellitus (DM) is associated with pathological changes in the central nervous system (CNS) and alterations in oxidative stress. The aim of this study was to determine whether dietary supplement with whey protein (WP) could improve neurobehavior, oxidative stress and neuronal structure in the CNS. Animals were distributed in three groups, a control group (N), a diabetic mellitus group (DM) and a DM group orally supplemented with WP (WP). The DM group of animals receiving WP had reduced blood glucose, significantly decreased free radical Diphenyl-picrylhydrazyl (DPPH) and lower lipid peroxidation in brain tissue. The WP group of animals showed improvement in balancing, coordination and fore-limb strength, oxidative stress and neuronal structure. The results of this study show that dietary supplementation with WP reduced oxidative stress, protected CNS neurons and improved the neurobehavior of diabetic mice.