Immunological Stress Research Articles

Rutin protects against cyclophosphamide induced immunological stress by inhibiting TLR4-NF-κB-mediated inflammation and activating the Nrf2- mediated antioxidant responses

Rutin exists in many plants and has many pharmacological effects, including antioxidant, anti-inflammatory, antibacterial and immune regulation. In this study, the immunomodulatory and antioxidant effects of rutin were revealed by cyclophosphamide (CTX) induced mice model. The expression level of the related genes and proteins was investigated by quantification real-time PCR and Western blotting methods, respectively. The results shown that rutin could significantly improve the damage of spleen and thymus caused by CTX, and very significantly (P<0.01) reduce the increasing content of TNF-α and IL-6. It also could significantly (P<0.01) decrease the relative expression level of TLR4, MyD88, TRAF6, and p65 genes and proteins, and significantly increase (P<0.01) the expression of IκB gene, phosphorylated p65 and IκB proteins. Moreover, rutin could significantly (P<0.01) reduce the MDA content and enhance the SOD activity, and increase the expression levels of Nrf2, HO-1 genes and proteins in the livers. In conclusion, rutin can regulate the secretion of cytokines and protect immune organs by regulation the expression level of the related genes and proteins in the TLR4-MyD88-NF-κB signaling pathway; and it can also play an antioxidative stress role by activation of the Nrf2/HO-1 signaling pathway. This research will lay a certain foundation for the screening of immunomodulators and antioxidants.

Rubber (Hevea brasiliensis) seed oil supplementation attenuates immunological stress and inflammatory response in lipopolysaccharide-challenged laying hens

This study was conducted to investigate the effect of PUFA-enriched rubber (Hevea brasiliensis) seed oil (RSO) supplementation in diets on the productive performance, plasma biochemical parameters, immune response, and inflammation in lipopolysaccharide (LPS)-challenged laying hens. Two hundred and forty 25-wk-old Lohmann Brown laying hens were randomly divided into 5 treatments, each including 4 replicates with 12 birds per replicate. The control group and LPS-challenged group were fed a corn-soybean-basal diet; 3 RSO-supplemented groups were fed experimental diets containing 1, 2, and 4% RSO for a feeding period of 4 wk. On the 15, 18, 21, 24, and 27 d of the RSO supplementation period of 4 wk, hens were injected intraperitoneally with LPS at 1 mg/kg body weight (challenge group and RSO-supplemented groups) or with the same amount of saline (control group). The results showed that the addition of RSO promoted laying performance by increasing egg production, total egg weight, daily egg mass, and feed intake in comparison to the LPS-challenged laying hens (P < 0.05). In addition, compared with laying hens stimulated with LPS, the analysis of blood cell and plasma parameters revealed that hens in RSO-supplemented groups had significantly lower levels (P < 0.05) of white blood cells (WBC), lymphocytes (LYM), aspartate aminotransferase (AST) activity, immunoglobulin A (IgA), triiodothyronine (T3), interleukin-2 (IL-2), and tumor necrosis factor-α (TNF-α). Further, RSO supplementation significantly reduced the mRNA expression of toll-like receptor 4 (TLR4), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), interleukin-6 (IL-6), and interleukin-1β (IL-1β) of the ileum, spleen, and liver in LPS-challenged laying hens (P < 0.05), suggesting that the anti-inflammatory mechanism of RSO is related to the TLR4/NF-κB signaling pathway. In conclusion, RSO supplementation in diets could improve laying performance, attenuate immunological stress, and inhibit the inflammatory response in LPS-challenged laying hens, especially at the dietary inclusion of 4% RSO. This study will provide an insight into the application of RSO to positively contribute to overall health and welfare in laying hens.

Glycerol monolaurate attenuated immunological stress and intestinal mucosal injury by regulating the gut microbiota and activating AMPK/Nrf2 signaling pathway in lipopolysaccharide-challenged broilers.

This study was conducted to investigate the effects of glycerol monolaurate (GML) on lipopolysaccharide (LPS)-induced immunological stress and intestinal mucosal injury in broilers and its underlying mechanisms. A total of 144 one-d-old Arbor Acres broilers were allocated to a 2 × 2 factorial arrangement involving dietary treatment (0 or 1,200 mg/kg dietary GML) and LPS challenge (injected with saline or Escherichia coli LPS on d 16, 18, and 20). Samples were collected on d 21. The results revealed that dietary GML augmented serum immunoglobulin A (P = 0.009) and immunoglobulin G (P < 0.001) levels in challenged birds. Dietary GML normalized LPS-induced variations in serum interleukin-6, interferon-gamma, and LPS levels (P < 0.05), jejunal villus height (P = 0.030), and gene expression of interleukin-6, macrophage inflammatory protein-3 alpha, Toll-like receptor 4, nuclear factor kappa-B, caspase-1, tight junction proteins, adenosine monophosphate-activated protein kinase alpha 1 (AMPKα1), nuclear factor-erythroid 2-related factor 2 (Nrf2), and superoxide dismutase-1 (P < 0.05). GML supplementation ameliorated LPS-induced peroxidation by reducing malondialdehyde content and increasing antioxidant enzyme activity (P < 0.05). Dietary GML enhanced the abundances of Anaerostipes, Pseudoflavonifractor, and Gordonibacter and reduced the proportion of Phascolarctobacterium in challenged birds. Dietary GML was positively correlated with alterations in antioxidant enzyme activities and AMPKα1, Nrf2, and zonula occludens-1 expressions. The genera Anaerostipes, Lachnospira, Gordonibacter, Lachnospira, Marvinbryantia, Peptococcus, and Pseudoflavonifractor were linked to attenuated inflammation and improved antioxidant capacity of challenged birds. In conclusion, dietary GML alleviated LPS-induced immunological stress and intestinal injury of broilers by suppressing inflammation and oxidative stress. Dietary GML regulated cecal microbiota and activated the AMPK/Nrf2 pathway in LPS-challenged broilers.

C1QTNF3 is Upregulated During Subcutaneous Adipose Tissue Remodeling and Stimulates Macrophage Chemotaxis and M1-Like Polarization.

The adipose tissue undergoes substantial tissue remodeling during weight gain-induced expansion as well as in response to the mechanical and immunological stresses from a growing tumor. We identified the C1q/TNF-related protein family member C1qtnf3 as one of the most upregulated genes that encode secreted proteins in tumor-associated inguinal adipose tissue - especially in high fat diet-induced obese mice that displayed 3-fold larger tumors than their lean controls. Interestingly, inguinal adipose tissue C1qtnf3 was co-regulated with several macrophage markers and chemokines and was primarily expressed in fibroblasts while only low levels were detected in adipocytes and macrophages. Administration of C1QTNF3 neutralizing antibodies inhibited macrophage accumulation in tumor-associated inguinal adipose tissue while tumor growth was unaffected. In line with this finding, C1QTNF3 exerted chemotactic actions on both M1- and M2-polarized macrophages in vitro. Moreover, C1QTNF3 treatment of M2-type macrophages stimulated the ERK and Akt pathway associated with increased M1-like polarization as judged by increased expression of M1-macrophage markers, increased production of nitric oxide, reduced oxygen consumption and increased glycolysis. Based on these results, we propose that macrophages are recruited to adipose tissue sites with increased C1QTNF3 production. However, the impact of the immunomodulatory effects of C1QTNF3 in adipose tissue remodeling warrants future investigations.

Zinc oxide, titanium dioxide and C60 fullerene nanoparticles, alone and in mixture, differently affect biomarker responses and proteome in the clam Ruditapes philippinarum

Continuous release of nanoparticles (NPs) into marine coastal environments results in an increased risk of exposure to complex NP mixtures for marine organisms. However, to date, the information on the effects at molecular and biochemical levels induced by the exposure to NPs, singly and as a mixture, is still scant. The present work aimed at exploring the independent and combined effects and the mechanism(s) of action induced by 7-days exposure to 1 μg/L nZnO, 1 μg/L nTiO2 and 1 μg/L FC60 fullerene in the Manila clam Ruditapes philippinarum, using a battery of immunological and oxidative stress biomarkers in haemolymph, gills and digestive gland. In addition, proteomics analyses were performed in gills and the digestive gland, where NP bioaccumulation was also assessed. Increased bioaccumulation of single NPs and the mixture was linked with increased oxidative stress and higher damage to proteins, lipids and DNA in all tissues analysed. The proteomics approach highlighted protein modulation in terms of abundance and damage (higher redox-thiol and carbonylated groups content). In particular, the modulated proteins (16 in gills and 18 in digestive gland) were mostly related to cytoskeleton and energetic metabolism. The digestive gland was the tissue more affected. For all biomarkers measured, increased detrimental effects were observed in the mixture compared to single NP exposures.

Ginsenoside Rg3 Ameliorates Stress of Broiler Chicks Induced by Escherichia coli Lipopolysaccharide.

In broiler chicks, Escherichia coli lipopolysaccharide is a prominent cause for inflammatory damage and loss of immune homeostasis in broiler chicks. Ginsenosides have been shown to have anti-inflammatory and antioxidant effects. However, it has not been demonstrated that ginsenosides protect broiler chicks against stress induced by Escherichia coli lipopolysaccharide challenge. The aim of this is to investigate the protective effect of ginsenosides Rg1, Re, and Rg3 on Escherichia coli lipopolysaccharide-induced stress. Our results showed that Rg3 ameliorated growth inhibition and fever, as well as decreased the production of stress-related hormones in broilers with stress. The protective effect of Rg3 on the stressed chicks may be largely mediated by regulating inflammatory response and oxidative damage. Moreover, real-time quantitative-polymerase chain reaction (RT-qPCR) results demonstrated that Rg3 upregulated mRNA expression of mTOR, HO-1, and SOD-1. These results suggested that ginsenoside Rg3 and ginsenoside products contains Rg3 deserve further study for the control of immunological stress and inflammation in broiler chicks.

CD8+ T Cell Senescence: Lights and Shadows in Viral Infections, Autoimmune Disorders and Cancer.

CD8+ T lymphocytes are a heterogeneous class of cells that play a crucial role in the adaptive immune response against pathogens and cancer. During their lifetime, they acquire cytotoxic functions to ensure the clearance of infected or transformed cells and, in addition, they turn into memory lymphocytes, thus providing a long-term protection. During ageing, the thymic involution causes a reduction of circulating T cells and an enrichment of memory cells, partially explaining the lowering of the response towards novel antigens with implications in vaccine efficacy. Moreover, the persistent stimulation by several antigens throughout life favors the switching of CD8+ T cells towards a senescent phenotype contributing to a low-grade inflammation that is a major component of several ageing-related diseases. In genetically predisposed young people, an immunological stress caused by viral infections (e.g., HIV, CMV, SARS-CoV-2), autoimmune disorders or tumor microenvironment (TME) could mimic the ageing status with the consequent acceleration of T cell senescence. This, in turn, exacerbates the inflamed conditions with dramatic effects on the clinical progression of the disease. A better characterization of the phenotype as well as the functions of senescent CD8+ T cells can be pivotal to prevent age-related diseases, to improve vaccine strategies and, possibly, immunotherapies in autoimmune diseases and cancer.

Hematopoietic stem and progenitor cells improve survival from sepsis by boosting immunomodulatory cells

New therapeutic strategies to reduce sepsis-related mortality are urgently needed, as sepsis accounts for one in five deaths worldwide. Since hematopoietic stem and progenitor cells (HSPCs) are responsible for producing blood and immune cells, including in response to immunological stress, we explored their potential for treating sepsis. In a mouse model of Group A Streptococcus (GAS)-induced sepsis, severe immunological stress was associated with significant depletion of bone marrow HSPCs and mortality within approximately 5-7 days. We hypothesized that the inflammatory environment of GAS infection drives rapid HSPC differentiation and depletion that can be rescued by infusion of donor HSPCs. Indeed, infusion of 10,000 naïve HSPCs into GAS-infected mice resulted in rapid myelopoiesis and a 50-60% increase in overall survival. Surprisingly, mice receiving donor HSPCs displayed a similar pathogen load compared to untreated mice. Flow cytometric analysis revealed a significantly increased number of myeloid-derived suppressor cells in HSPC-infused mice, which correlated with reduced inflammatory cytokine levels and restored HSPC levels. These findings suggest that HSPCs play an essential immunomodulatory role that may translate into new therapeutic strategies for sepsis.

Interplay between stress and immunity triggers herpes zoster infection in COVID-19 patients: a review.

Coronavirus disease 2019 (COVID-19) is a potential health threat in the highly mobile society of the world. There are also concerns regarding the occurrence of co-infections occurring in COVID-19 patients. Herpes zoster (HZ) is currently being reported as a co-infection in COVID-19 patients. It is a varicella-zoster virus induced viral infection affecting older and immunocompromised individuals. Reactivation of HZ infection in COVID-19 patients are emerging and the mechanism of reactivation is still unknown. The most convincing argument is that increased psychological and immunological stress leads to HZ in COVID-19 patients; this review justifies this argument.

Impact of lactoferrin supplementation on oxidative stress, gene expression and immunity dysfunction induced by Aeromonas veronii in Nile tilapia ( Oreochromis niloticus )

This study investigated the effect of bovine lactoferrin (LF) dietary supplementation on haematological and immunological parameters, antioxidant genes, stress markers and disease resistance in Nile tilapia (Oreochromis niloticus) compared with that of oxytetracycline. Experimental fish were allocated into different groups as follows: Group 1, the control group, was fed a basal diet without any additives; Group 2 was fed a diet containing LF at a dose of 800 mg/kg; Group 3 was fed a diet containing LF at a dose of 1200 mg/kg; and Group 4 was fed a diet containing oxytetracycline (500 mg/kg diet) daily for 30 days to compare their effects before infection with Aeromonas veronii on the 15th day of the experiment and after infection on the 30th day of the experiment. Total white blood cell count, heterophils, IgG and total antioxidant capacity were not affected by dietary supplementation with either LF or oxytetracycline before infection. However, there was an interface between dietary LF supplementation with either 800 or 1200 mg/kg in improving haematological and immunological parameters and decreasing stress markers before and after infection. Expression profile of renal and splenic inflammatory (IL-10, IFN-γ, IL1b, TLR9, TNF-α, IL-21, IL-6 and Caspase3) markers was also upregulated compared with those in the control and oxytetracycline groups. The modulated expression profile of hepatic antioxidant (CAT, SOD, GPx, Nrf2i and Keap1) markers was significantly upregulated compared with those in the control and oxytetracycline groups. However, Keap1 seemed to be downregulated.

Dietary chitooligosaccharide supplementation alleviates intestinal barrier damage, and oxidative and immunological stress in lipopolysaccharide-challenged laying hens

This study aimed to investigate the effects of chitooligosaccharide (COS) on intestinal barrier, antioxidant capacity, and immunity of lipopolysaccharide (LPS)-challenged laying hens. A total of 360 Hy-line Brown laying hens (80-wk-old) were randomly divided into 5 groups with 6 replicates of 12 birds. Hens were fed a corn-soybean meal basal diet supplemented with different COS levels (0; 5; 10; 15; 20 mg/kg) for 8 wk. The results showed that 15 mg/kg COS administration elevated albumen height and Haugh unit (P < 0.05), and numerically optimized productive performance (P > 0.05), therefore, the dosage of 15 mg/kg was chosen for the subsequent experiment. Thereafter, 12 birds from non-supplemented group were randomly selected and assigned into 2 groups, and birds in each group were administered (1.5 mg/kg BW, i.p.) with saline (control group) or LPS (challenge group). Another 6 hens from 15 mg/kg COS-supplemented group were selected and injected with LPS in the same way. Compared with the control group, LPS-challenged birds exhibited elevated circulating diamine oxidase activity, and reduced jejunal villus height and ratio of villus height to crypt depth, and these indices were reversed to control levels by COS (P < 0.05). Also, LPS increased malondialdehyde accumulation and reduced several antioxidant enzyme activities in the intestinal mucosa (P < 0.05). Additionally, LPS increased jejunal secretory IgA and interferon-γ (IFN-γ), and ileal secretory IgA, IgM, and interleukin-1β (IL-1β) concentrations, whereas COS reduced jejunal IFN-γ and IL-1β, and ileal IgM levels (P < 0.05). Moreover, LPS down-regulated mRNA abundance of jejunal occludin and claudin 2, and upregulated expression of jejunal nuclear factor erythroid-2 related factor 2, superoxide dismutase 1, and IFN-γ as well as ileal IL-1β (P < 0.05). Besides, COS increased jejunal occludin and ileal claudin 2, nuclear factor erythroid-2 related factor 2, and heme oxygenase-1 expression, and decreased jejunal IFN-γ and IL-1β abundance (P < 0.05). These results suggested that COS could alleviate LPS-induced intestinal barrier impairment, and oxidative and immunological stress in laying hens.

Determination of the relationship between major histocompatibility complex alleles and childhood onset obsessive-compulsive disorder.

About half of the cases of obsessive-compulsive disorder (OCD) occurring in childhood/adolescence occur with similar symptoms both in childhood and adulthood. Immunologic stress is claimed to be a risk factor in the etiology of childhood onset OCD. Our aim was to elucidate the relationship between childhood onset OCD risk and MHC complex I and II alleles. MHC alleles of 49 OCD children together with 277 healthy children (aged 4-12) were analyzed by PCR. Results were evaluated by using univariate analysis and multivariate logistic regression analysis. A2, A29, C4, DRB3.1, and DRB1*16 alleles were found to increase the risk of OCD. The relationship found between DRB locus and OCD in this study was remarkable since there have been studies on different populations reporting similar relationship between DRB locus and rheumatoid arthritis, which is also an AID. MHC class I and class II alleles were found to increase the risk of OCD in our study, which serves as a suitable model for studies suggesting that MHC genes do not work completely independently. Even though the MHC class I and II genes are considered to have different roles in immune response, in fact they tend to work in cooperation. As in previous studies on AIDs, there is a linear relationship between MHC class II alleles and OCD risk.

Terazosin Stimulates Pgk1 to Remedy Gastrointestinal Disorders.

Gastrointestinal disease is the most common health concern that occurs due to environmental, infectious, immunological, psychological, and genetic stress. Among them, the most frequent diseases are gastric ulcer (GU) and ulcerative colitis (UC). DSS-induced UC and ethanol-stimulated GU models resemble the pathophysiology of human gastrointestinal disease. The current study was designed to explore the anti-oxidation, anti-inflammation, anti-cell death properties of terazosin, an α-adrenergic receptor antagonist, in vivo and in vitro. Our results indicate that terazosin dramatically activates Pgk1, and upregulates glycose metabolism, evidenced by the enhanced ATP production and higher LDH enzymatic activity. Also, terazosin significantly enhances p-AKT expression and inhibits NF-κB p65 activation through abrogating the phosphorylation of IKBα, as well as lowers Caspase-1 and GSDMD expression. The findings in this study demonstrate that terazosin exhibits anti-inflammatory effects by downregulating NF-κB-GSDMD signal pathway, along with enhancing glycolysis for gastrointestinal disease treatment. Meanwhile, we also find terazosin ameliorates ethanol-induced gastric mucosal damage in mice. Collectively, as a clinical drug, terazosin should be translated into therapeutics for gastrointestinal disease soon.

Effect of Pandanus tectorius extract as food additive on oxidative stress, immune status, and disease resistance in Cyprinus carpio

The present study investigated the effect of Pandanus tectorius (PT) extract on Cyprinus carpio growth, antioxidant capacity, immunological and oxidative stress, immune-related gene expression, and resistance against pathogen challenge. Fish (average weight: 12.18 ± 0.32 g) were fed with diets containing various concentration (g kg−1) of PT extract: 0 g (basal diet), 5 g [PT5], 10 g [PT10], 20 g [PT20], and 30 g [PT30] for 8 weeks. Our results revealed an increase (p < 0.05) in the final weight gain only in the PT20 (63.12 ± 1.4 g) group. Activity of liver antioxidant parameters such as catalase (CAT) (27.67 ± 1.12 U mg protein−1), superoxide dismutase (SOD) (13.17 ± 0.428 U mg protein−1), and glutathione peroxidase (GPx) (47.14 ± 1.47 U mg protein−1) was highest in the PT20 group. Among the serum immunological parameters examined, lysozyme (37.45 ± 0.67 U mL−1), alternative complement pathway (133.22 ± 1.92 U mL−1), and phagocytic activities (25.68 ± 0.93%) were high (p < 0.05) in PT20, whereas there was no significant effect on serum immunoglobulin or total protein levels, compared to the control. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and malondialdehyde (MDA) levels were found to be lower (p < 0.05) in the PT20 and PT30 groups than those in the control. However, myeloperoxidase (MPO) levels were significantly higher (p < 0.05) in the PT20 and PT30 groups. Gene expression analysis revealed that mRNA expressions of antioxidant genes (SOD, CAT, nuclear factor erythroid 2-related factor 2) and anti-inflammatory cytokine (IL-10) genes were significantly upregulated in the PT10 – PT30 groups, except for the SOD gene in PT10. Conversely, the signalling molecule NF-κBp65 was downregulated in PT20 and PT30. Expression of Toll-like receptor 22 (TLR22) and hepcidin was significantly upregulated in PT20 and PT30, respectively. Fish in the PT20 group exhibited highest relative post-challenge survival (70.37%) against Aeromonas hydrophila challenge. The results of the present study suggest that dietary supplementation of P. tectorius extract at 20 g kg−1 can significantly improve weight gain, serum antioxidant parameters, strengthen immunity, and increase the disease resistance of C. carpio. Therefore, P. tectorius extract could be exploited for its use as a food additive in aquaculture.

The Effects of Ursolic Acid Treatment on Immunopathogenesis Following Mannheimia haemolytica Infections.

Bovine respiratory disease complex (BRDC) is a costly economic and health burden for the dairy and feedlot cattle industries. BRDC is a multifactorial disease, often involving viral and bacterial pathogens, which makes it difficult to effectively treat or vaccinate against. Mannheimia haemolytica (MH) are common commensal bacteria found in the nasopharynx of healthy cattle; however, following environmental and immunological stressors, these bacteria can rapidly proliferate and spread to the lower respiratory tract, giving rise to pneumonic disease. Severe MH infections are often characterized by leukocyte infiltration and dysregulated inflammatory responses in the lungs. IL-17A is thought to play a key role in this inflammatory response by inducing neutrophilia, activating innate and adaptive immune cells, and further exacerbating lung congestion. Herein, we used a small molecule inhibitor, ursolic acid (UA), to suppress IL-17A production and to determine the downstream impact on the immune response and disease severity following MH infection in calves. We hypothesized that altering IL-17A signaling during MH infections may have therapeutic effects by reducing immune-mediated lung inflammation and improving disease outcome. Two independent studies were performed (Study 1 = 32 animals and Study 2 = 16 animals) using 4-week-old male Holstein calves, which were divided into 4 treatment group including: (1) non-treated and non-challenged, (2) non-treated and MH-challenged, (3) UA-treated and non-challenged, and (4) UA-treated and MH-challenged. Based on the combined studies, we observed a tendency (p = 0.0605) toward reduced bacterial burdens in the lungs of UA-treated animals, but did not note a significant difference in gross (p = 0.3343) or microscopic (p = 0.1917) pathology scores in the lungs. UA treatment altered the inflammatory environment in the lung tissues following MH infection, reducing the expression of IL-17A (p = 0.0870), inflammatory IL-6 (p = 0.0209), and STAT3 (p = 0.0205) compared to controls. This reduction in IL-17A signaling also appeared to alter the downstream expression of genes associated with innate defenses (BAC5, DEFB1, and MUC5AC) and lung remodeling (MMP9 and TIMP-1). Taken together, these results support our hypothesis that IL-17A signaling may contribute to lung immunopathology following MH infections, and further understanding of this inflammatory pathway could expand therapeutic intervention strategies for managing BRDC.

Effects of dietary supplementation with Artemisia argyi alcohol extract on growth performance, blood biochemical properties and small intestinal immune markers of broilers challenged with lipopolysaccharide

Context Broilers are prone to immunological stress when subjected to unsuitable environmental conditions (such as virus attack, nutrient deficiency and high stocking density), lowering immunity and resulting in inflammatory bowel diseases. The herb-feed additive Artemisia argyi has been applied in poultry production, and its extract may improve small intestinal immune capacity. Aims This study was conducted to investigate the effect of A. argyi alcohol extract (AAAE) on growth performance and blood biochemical and small intestinal immune markers of broilers challenged with a proinflammatory substance, lipopolysaccharide (LPS). The study also examined possible mechanisms of action, and aimed to clarify whether AAAE could be applied as a feed additive. Methods In total, 192 one-day-old Arbor Acres broilers were allocated to four groups following a 2 × 2 factorial arrangement (including six replicates with eight birds per replicate) with two dietary AAAE rates (0 or 750 mg/kg) and two immune stress treatments (LPS or saline injection). Blood and small intestine were sampled on Days 21 and 35. Key results Dietary AAAE alleviated the LPS-induced decrease in bodyweight, average daily gain and average daily feed intake, and mitigated the elevated serum alanine aminotransferase, triglyceride, low-density lipoprotein cholesterol, adrenocorticotropic hormone and corticosterone concentrations at Day 21 and/or Day 35 in LPS-challenged broilers. AAAE significantly (P &lt; 0.05) attenuated LPS-induced increases in intestinal immunoglobulin (IgA, IgG and IgM) and interleukin (IL-1β and IL-6) concentrations. Moreover, the small intestinal mRNA abundances of the genes TLR4, MyD88, NF-κBp65, IL-1β and IL-6 in LPS-challenged broilers were decreased (P &lt; 0.05) in response to dietary AAAE treatment. Conclusions These results further demonstrated that AAAE at 750 mg/kg enhanced small intestinal tissue immune capacity of broilers, thereby alleviating LPS-induced immune stress damage in broilers. Its mechanism of action may be related to the mediating of TLR4/NF-κB pathways. Implications Dietary AAAE can be used to improve the immune function of broilers, and to provide a new scientific theoretical basis for the development of new anti-stress feed additives.

The costs of coping: Different strategies to deal with social defeat stress might come with distinct immunologic, neuroplastic, and oxidative stress consequences in male Wistar rats.

The impact of stress on health and well-being is determined by the ability of an individual to cope with challenges imposed by the stressor. Animals exposed to social defeat stress show different patterns of response during confrontations, leading to distinct stress-induced consequences. Using an established resident-intruder paradigm, we explored the outcomes of adopting active or passive coping strategies during a social defeat protocol over peripheral and central nervous system (CNS) levels of inflammatory cytokines, growth factors, glucocorticoid, and oxidative stress markers in male Wistar rats. Animals that presented short latency to assume a defeated posture during confrontation-considered as susceptible to stress-exhibited increased levels of brain-derived neurotrophic factor (BDNF) in the amygdala (AMY) and in the bed nucleus of the stria terminalis (BNST), and decreased lipid peroxidation in the CNS, suggesting changes in antioxidative defenses as well as stress-induced neuroadaptations. On the other hand, animals with longer latencies to assume a submissive posture-considered to be resilient to stress-presented lower levels of CNS BDNF compared to short-latency animals and decreased enzymatic antioxidant defenses in the CNS in comparison to controls, which might indicate an increased risk of central oxidative damage. From the results, behavioral reactivity cannot be considered a predictor of success in responding to stress; however, the findings of this study reinforce the idea that exposure to stress has no predetermined negative effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Intrathecal Nalbuphine versus Intrathecal fentanyl as adjuvant to 0.5% bupivacaine for caesarian section surgery under subarachnoid block

Abstract Background One of the main objectives of anesthesia is to relieve the patient’s pain and agony, by ensuring the performance of surgical procedures without any discomfort. Elimination of postoperative pain is indispensable due to the central, peripheral and immunological stress response to tissue injury. So there is a need for extended analgesia without any side effects to achieve this goal. Aim of the Work To compare the post-operative analgesic effect of intrathecal-nalbuphine and fentanyl as adjuvant to bupivacaine during cesarean delivery. The secondary aim is to compare side effects between using nalbuphine and fentanyl as adjuvants to bupivacaine. Patients and Methods After Approval is obtained from the research Medical Ethical Committee of Faculty of Medicine, Ain Shams University. The study was conducted on 60 patients that were randomly selected. Randomly divided into 2 groups 30 patients each. Group F which received fentanyl as adjuvant while group N received nalbuphine as adjuvant. Results The addition of a small dose of nalbuphine or fentanyl to bupivacaine in spinal anesthesia prolonged the time of postoperative analgesia. In this study, there was no significant difference regarding the age, height, weight, and duration of operation, maximum sensory level, and maximum motor blockade level. The duration of the postoperative analgesia was prolonged with Nalbuphine group in comparison to the fentanyl group, the results were highly significant. Conclusion We concluded that either intrathecal nalbuphine (0.8 mg) or intrathecal fentanyl (25 µg) combined with Bupivacaine improves intraoperative analgesia and prolongs early post-operative analgesia in cesarean section. There was no significant difference with regard to: Peak sensory block level, Maximum motor block level, systolic blood pressure, diastolic blood pressure, oxygen saturation, and heart rate.

Overnight Immune Regulation and Subjective Measures of Sleep: A Three Night Observational Study in Adolescent Track and Field Athletes.

To ensure health maintenance of young athletes, immunological stress due to physical exercise has to be balanced for performance development and health maintenance. Sleep is an important influencing factor for immune regulation because of its regenerating effect. In an attempt to assess overnight immune regulation, this observational study aimed to examine associations between changes in capillary immunological blood markers and measures of sleep in adolescent athletes. Over a period of three nights, 12 male (n = 6) and female (n = 6) adolescent track and field athletes aged 16.4 ± 1.1 years were monitored for their sleep behavior (e.g., sleep duration, sleep depth) and immune regulation by using subjective (e.g., sleep) and objective (capillary blood markers) measurement tools. Over the 4 day (three nights), athletes followed their daily routines (school, homework, free time activities, and training). Training was performed for different disciplines (sprint, hurdles, and long-jump) following their daily training routines. Training included dynamic core stability training, coordination training, speed training, resistance training, and endurance training. Capillary blood samples were taken 30–45 min after the last training session (10:00–12:00 a.m. or 5:00–6:00 p.m.) and every morning between 7:00 and 10:00 a.m. Changes in capillary blood markers from post-training to the next morning and morning-to-morning fluctuations in capillary blood markers were analyzed over a three-night period using a generalized estimating equations (GEE) statistical approach. Associations of overnight changes with measures of sleep were analyzed using GEE. We found significant decreases in white blood cell count (WBC), granulocytes (GRAN), granulocytes% (GRAN%), monocytes (MID), and granulocyte-lymphocyte-ratio. In contrast, lymphocytes% (LYM%) increased significantly and systemic inflammation index showed no difference from post-training to the next morning. Furthermore, there was a significant decrease in WBC and GRAN between morning 1 and morning 3. At morning 4, values returned to baseline (morning 1), irrespective if athletes performed a training session or rested on day 3. Furthermore, sleep duration was significantly and negatively associated with changes in WBC (βz = −0.491) and lymphocytes (βz = −0.451). Our results indicate that overnight sleep duration is an important parameter of immunological overnight regulation for adolescent athletes.

MicroRNA expression profile in Lampetra morii upon Vibrio anguillarum infection and miR-4561 characterization targeting lip

As a critical evolutionary pivot between invertebrates and vertebrates, lampreys provide rich genetic information. Lamprey immune protein (LIP) is a key immune regulator. MicroRNAs, well-conserved in the response to immunological stress, remain understudied in lamprey immunity. We generated a lamprey microRNA expression atlas, using deep sequencing, upon Vibrio anguillarum infection. Using comparative methods, we found that miR-4561 potentially regulates innate immunity via interaction with lip. We found a sequence in the 3′-UTR region of LIP mRNA complementary to the miR-4561 seed region; miR-4561 expression was negatively correlated with LIP. During V. anguillarum infection, miR-4561 inhibited LIP expression and bacterial clearance. Notably, LIP expression in supraneural body cells was necessary for the Gram-negative immune response. Additionally, we observed that overexpression of miR-4561 induced apoptosis in embryonic cells, suggesting a role in embryonic development. Collectively, we show lamprey microRNAs may significantly affect gene regulation and provide new insights on LIP-mediated immune regulation.