Immunological Stress Research Articles

The association between salivary IL-6 and poor sleep quality assessed using Apple watches in stressed workers in Japan.

Insomnia is a major concern among stressed workers worldwide. Although stress generally has a detrimental effect on sleep quality, the impact of biological stress, especially the immunological stress response, on sleep quality is not yet fully understood. Stressed workers were recruited through a screening process using a Brief Job Stress Questionnaire. The participants were asked to complete various occupation-related questionnaires. Additionally, saliva samples were collected to assess interleukin-6 (IL-6) levels as an immunological stress response. Subsequently, they were asked to wear an Apple Watch to record their sleep pattern for one week. Their sleep architecture was estimated using a previously published and validated method. Finally, data from 73 participants were analyzed. Our multivariable analysis revealed that shorter durations of slow-wave sleep (non-rapid eye movement sleep stage 3) were significantly associated with elevated IL-6 levels (p = 0.005) and greater daytime sleepiness (p = 0.002) after controlling for total sleep time. Our finding that a higher immunological stress response is associated with poor sleep quality contributes to a better understanding of insomnia in stressed workers and emphasizes the importance of stress management in this population.

High doses of radiation cause cochlear immunological stress and sensorineural hearing loss

Radiotherapy is a crucial treatment for head and neck malignancies, but it can sometimes cause sensorineural hearing loss (SNHL). Changes in the immune microenvironment and sensory neuroepithelium of the inner ear after radiation exposure remain poorly understood. This study investigated cochlear morphology and macrophages in the inner ear after high-dose irradiation. The heads of heterozygous 8-week-old Cx3cr1GFP/+ male mice were irradiated with 30Gy of X-rays and biological samples were collected on days 1, 7, and 10 after irradiation. Auditory brainstem responses were used to assess auditory function in the mice. Changes in basilar membrane hair cells, spiral ganglion neurons (SGN), and inner ear macrophages were observed using hematoxylin-eosin (HE) staining and immunofluorescence staining. The expression of inflammatory mediators in the inner ear was detected by quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) in cochlear tissue. The results showed no significant hair cell loss after a single high dose of radiation. However, the mice developed pantonal hearing loss on day 10 when HE staining revealed SGN atrophy and immunofluorescence showed decreased neurofilament expression. The number of macrophages in the inner ear reduced over time. RT-qPCR showed that cochlear inflammatory factors and chemokines were briefly upregulated on day 1st after irradiation and then decreased over time. In conclusion, high-dose irradiation causes acute SNHL that is not associated with hair cell loss and may be related to SGN changes. Radiation-induced SNHL is associated with a reduction in cochlear macrophages and changes in the immune microenvironment, but the relationship between the two remains to be investigated.

Exploring the Multifactorial Pathophysiology of Vitiligo: Genetic, Immunological, and Oxidative Stress Interactions

Exploring the Multifactorial Pathophysiology of Vitiligo: Genetic, Immunological, and Oxidative Stress Interactions

Investigating intraspecific variability in the biological responses of sea urchins (Paracentrotus lividus) to seawater acidification

Alterations in seawater chemistry posed by acidification may lead to immunological and antioxidant defence impairment in sea urchins, with differences among local populations. Here, we analyzed the effects of reduced pH on Paracentrotus lividus, with a multibiomarker approach, and the possible intraspecific variations in sea urchin responses. Two groups of animals with different ecological histories (i.e., the pattern of environmental characteristics and pressures experienced throughout the organism’s lifetime) were maintained at ambient pH and pH reduced of 0.4 units for 8 months. Changes in gonadosomatic index (GSI), immunological, and oxidative stress biomarkers were assessed in coelomic fluid, gonads, and digestive tract. Animals maintained at reduced pH showed limited impact of seawater acidification compared to the ambient pH condition. However, sea urchins from the two sites were differently influenced by the seawater pH (as shown by multivariate analyses). GSI and immunological and antioxidant status were differentially modulated between the two sexes, with generally higher values in females, but differences between sexes in relation to the pH of exposure were limited. Overall, our findings highlight that the impact of environmental stressors may differ in sea urchins from different locations. This has implications for the maintenance of P. lividus wild populations under future global change scenarios.

The basic leucine zipper domain (bZIP) transcription factor BbYap1 promotes evasion of host humoral immunity and regulates lipid homeostasis contributing to fungal virulence in Beauveria bassiana.

Entomopathogenic fungi (EPF) offer an effective and eco-friendly alternative to curb insect populations in biocontrol strategy. When EPF enter the hemolymph of their host, they encounter a variety of stress reactions, such as immunological and oxidative stress. Basic leucine zipper domain transcription factors, of which yeast activator protein (Yap) is a significant class, have diverse biological functions related to metabolism, development, reproduction, conidiation, stress responses, and pathogenicity. This study demonstrates that BbYap1 of Beauveria bassiana regulates cellular enzyme lipid homeostasis and fungal virulence by eluding host humoral defense, which contributes to fungal chemical stress and vegetative development. These findings offer fresh perspectives for comprehending molecular roles of YAP in EPF.

Pubertal stress in male rats: Effects on juvenile play behavior and adult sexual partner preference

Puberty is a period of brain organization impacting the expression of social and sexual behaviors. Here, we assessed the effects of an acute pubertal stressor (immune challenge) on the expression of juvenile play (short-term) and sexual partner preference (long-term) in male rats. Juvenile play was assessed over ten trials at postnatal days (PND) (31–40) with age- and sex-matched conspecifics, and at PND35 males received a single injection of lipopolysaccharide (LPS, 1.5 mg/kg i.p.) or saline. Then, sexual partner preference was assessed at PND 60, 64, and 68, in a three-compartment chamber with a sexually receptive female and a male as potential partners simultaneously. The results confirmed that a single injection of LPS during puberty induced sickness signs indicative of an immune challenge. However, juvenile play was not affected by LPS treatment during the following days (PND36–40), nor was sexual behavior and partner preference for females in adulthood. These findings highlight that, while other studies have shown that LPS-induced immunological stress during puberty affects behavior and neuroendocrine responses, it does not affect juvenile play and sexual behavior in male rats. This suggests a remarkable resilience of these behavioral systems for adaptation to stressful experiences mediated by immune challenges during critical periods of development. These behaviors, however, might be affected by other types of stress.

Mechanisms of age-related ocular diseases: a comprehensive review with an emphasis on glaucoma

With aging, senescence-related diseases are increasing in prevalence. The senescence of cells in the central nervous system has been linked with the development of neurodegenerative diseases such as Alzheimer’s or Parkinson’s disease. These changes are not limited to the brain as many eye diseases, such as cataract, diabetic retinopathy, age-related macular degeneration, and glaucoma, are also age-related. Among them, glaucoma is one of the leading causes of irreversible blindness with a multifactorial neurodegenerative nature. Besides an elevated intraocular pressure, an increased age is one of the main risk factors for this disease. Hence, in this review, we will discuss age-related changes in the context of eye disease, with a specific focus on glaucoma. Several general aging mechanisms were put forward in different eye diseases. This includes dysregulated nutrient sensing, cellular senescence, stem cell exhaustion, altered intercellular communication, genomic instability, telomere shortening, epigenetic alteration, loss of proteostasis, compromised autophagy, and mitochondrial dysfunction. In glaucoma, aging is a main risk factor for the development. This is triggered by oxidative, metabolic, immunological, and biomechanical stressors with many cross-talks. Oxidative stress, for example, can also trigger apoptotic cell death through mitochondrial damage, hypoxia, inflammation, and endothelial dysregulation. Also, with advanced age, alterations in extracellular matrix composition and structure are becoming important biomechanical contributing factors to the pathology of glaucoma. All mentioned mechanisms triggered by aging processes are generally accepted as contributing factors in the development of glaucoma in the aged eye. A better understanding of these will help to find novel therapeutic approaches for glaucoma patients in the future.

Diploid and triploid Chinook salmon (Oncorhynchus tshawytscha) exhibit differential immunological responses toacute thermal stress.

Exposure to temperatures outside of a fish's optimal range results in suppression of the immune system, ultimately leaving aquaculture stocks susceptible to disease outbreaks. This effect is exacerbated in triploid fishes, which demonstrate greater susceptibility to stress than their diploid counterparts. This study investigates the impacts of acute heat stress on the abundance of immune transcripts and proteins in diploid and triploid Chinook salmon (Oncorhynchus tshawytscha), an important finfish crop. This study also demonstrates that acute heat stress induces significant increases in the abundance hsp70, hsp90 and il1b transcripts in the head kidneys, gills and heart ventricles of both diploid and triploid Chinook salmon. Widespread dysregulation of antigen-presentation transcripts was also observed in fish of both ploidies. These results suggest that acute heat stress activates acute-phase responses in Chinook salmon and dysregulates antigen presentation, potentially leaving fish more susceptible to infection. At the protein level, IL-1β was differentially expressed in the head kidney and ventricles of diploid and triploid salmon following heat shock. Differential expression of two tapasin-like proteins in diploid and triploid salmon subjected to heat shock was also observed. Altogether, these data indicate that diploid and triploid Chinook salmon respond differently to acute thermal stressors.

Role of Neurotransmitters in Steady State Hematopoiesis, Aging, and Leukemia.

Haematopoiesis within the bone marrow (BM) represents a complex and dynamic process intricately regulated by neural signaling pathways. This delicate orchestration is susceptible to disruption by factors such as aging, diabetes, and obesity, which can impair the BM niche and consequently affect haematopoiesis. Genetic mutations in Tet2, Dnmt3a, Asxl1, and Jak2 are known to give rise to clonal haematopoiesis of intermediate potential (CHIP), a condition linked to age-related haematological malignancies. Despite these insights, the exact roles of circadian rhythms, sphingosine-1-phosphate (S1P), stromal cell-derived factor-1 (SDF-1), sterile inflammation, and the complement cascade on various BM niche cells remain inadequately understood. Further research is needed to elucidate how BM niche cells contribute to these malignancies through neural regulation and their potential in the development of gene-corrected stem cells. This literature review describes the updated functional aspects of BM niche cells in haematopoiesis within the context of haematological malignancies, with a particular focus on neural signaling and the potential of radiomitigators in acute radiation syndrome. Additionally, it underscores the pressing need for technological advancements in stem cell-based therapies to alleviate the impacts of immunological stressors. Recent studies have illuminated the microheterogeneity and temporal stochasticity of niche cells within the BM during haematopoiesis, emphasizing the updated roles of neural signaling and immunosurveillance. The development of gene-corrected stem cells capable of producing blood, immune cells, and tissue-resident progeny is essential for combating age-related haematological malignancies and overcoming immunological challenges. This review aims to provide a comprehensive overview of these evolving insights and their implications for future therapeutic strategies.

Analgesic Effect of Intrathecal Nalbuphine versus Intrathecal Fentanyl as Adjuvant to 0.5% Bupivacaine for Cesarian Section under Spinal Anaesthesia

Abstract Background One of the main objectives of anesthesia is to alleviate 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. The use of opioids in intrathecal or epidural anesthesia has become common to increase postoperative analgesia. However, opioid-induced side effects, such as respiratory depression, nausea, vomiting, urinary retention and pruritus, limit their use. Objective To assess the postoperative analgesic requirements and the spinally mediated analgesic effects of intrathecal nalbuphine as an adjuvant to intrathecal bupivacaine after cesarean section in comparison to intrathecal bupivacaine with fentanyl. Methods This randomized comparative clinical trial was conducted in Ain Shams University Hospitals’ operating rooms on 48 patients undergoing cesarean section within a period of six months after approval of ethical committee of Faculty of Medicine, Ain Shams University. Results This study showed that 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 demographic data, duration of operation, maximum sensory level, and maximum motor blockade level. Adding to this, there was also no significant changes regarding the vital data of the patients. On the other hand, there was a significant difference regarding the duration of analgesia which was longer with nalbuphine. It was also noticed that with nalbuphine less patients required rescue analgesia in comparison to fentanyl. There was higher number of side effects recorded with fentanyl in comparison to nalbuphine. Conclusion Either intrathecal nalbuphine (0.8 mg) or intrathecal fentanyl (25 μg) combined with Bupivacaine improves intraoperative analgesia and prolongs post- operative analgesia in cesarean section. There was statistically significant difference between them, intrathecal nalbuphine had a prolonged duration of post-operative analgesia, lesser amount of rescue analgesia needed and fewer side effects than intrathecal fentanyl.

Comparative Study between Modified Pectoral Nerve Block versus Serratus Block for Analgesia For Modified Radical Mastectomy

Abstract Background One of the main objectives of anesthesia is to alleviate 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. Objective To assess the analgesic efficiency and safety of both Modified Pectoral Nerve Block versus Serratus Block in cases of modified radical mastectomy (MRM). The duration of analgesia and effect on hemodynamic parameters were evaluated. Moreover, undesirable side effects were studied. Patients and Methods The purpose of this study was to evaluate the effect of both PECS II block versus and Serratus anterior block in patients undergoing modified radical mastectomy surgery. The duration of analgesia and effect on hemodynamics parameters were evaluated. Moreover, undesirable side effects were studied. forty patients were randomly allocated into two equal groups (20 patients): group (A) and group (B). Group (A): received a PECSII block with 30 mL of bupivacaine 0.25%. Group(B): received a serratus anterior plane block (SAPB) using the same volume of 30 ml bupivacaine 0.25%. Results This study demonstrated that PECSII and serratus blocks have comparable analgesic properties in patients undergoing modified radical mastectomy. Both blocks were associated with reduced postoperative pain intensity and morphine consumption, intraoperative fentanyl requirement, and prolonged analgesia. The two blocks were associated with hemodynamic stability and absence of major complications characterizes both blocks. Conclusion This study confirms that PECSII and serratus blocks provide similarly adequate analgesia following modified radical mastectomy.

Protective effects of chlorogenic acid on the intestinal barrier of broiler chickens: an immunological stress model study

This study was conducted to investigate the protective effects of chlorogenic acid (CGA) on inflammatory responses and intestinal health of lipopolysaccharide (LPS)-challenged broilers. One hundred and forty-four 1-day-old male broiler chicks were divided into 3 groups with 6 replicates of 8 birds each. The groups were as follows: 1) Control group: birds fed a basal diet; 2) LPS group: LPS-challenged birds fed a basal diet; 3) CGA group: LPS-challenged birds fed a CGA-supplemented diet. The LPS was intraperitoneally administered at a dose of 1 mg/kg of body weight. CGA increased the weight gain and feed intake of LPS-challenged birds by 37.05% and 24.29%, respectively (P < 0.05). CGA also alleviated LPS-induced inflammation, as evidenced by lower levels of pro-inflammatory cytokines in the serum and jejunum (tumor necrosis factor-α, interferon-γ, interleukin-1β, and interleukin-6), and the decreased myeloperoxidase activity in the jejunum (P < 0.05). These effects were accompanied by a decrease in the mRNA abundance of toll-like receptor 4 and myeloid differentiation factor 88 and an inhibition of nuclear factor kappa-B translocation in the jejunum (P < 0.05). CGA reduced circulating diamine oxidase activity and levels of D-lactate and endotoxin, and positively regulated the expression of jejunal claudin-3 and zonula occludens-1 in LPS-challenged broilers (P < 0.05). Compared to the LPS group, CGA reduced the apoptotic rate of epithelial cells and cytochrome c concentration in the jejunum, and normalized the expression of genes responsible for proliferation and apoptosis in jejunal epithelial cells, including cysteine aspartate-specific protease-9, B cell lymphoma-2, and proliferating cell nuclear antigen (P < 0.05). Furthermore, CGA normalized the altered phosphorylation of protein kinase B and glycogen synthase kinase-3β, as well as the translocation of nuclear β-catenin in the jejunum of LPS-challenged broilers (P < 0.05). These results suggested that CGA supplementation improved growth performance, alleviated inflammation, and helped maintain intestinal integrity and barrier function in LPS-challenged broilers, possibly through the regulation of the toll-like receptor 4/nuclear factor kappa-B and protein kinase B/Wnt/β-catenin pathways.

Sea anemone-anemonefish symbiosis: Behavior and mucous protein profiling.

Fish species of the genus Amphiprion (Perciformes: Pomacentridae) seek protection from predators among the tentacles of sea anemones as their natural habitat, where they live essentially unharmed from stinging by the host's nematocysts. The skin mucus of these anemonefish has been suggested as a protective mechanism that prevents the discharge of the nematocysts upon contact. Whereas some anemonefish species seem to produce their own protective mucous coating, others may acquire mucus (or biomolecules within) from the sea anemone during an acclimation period. In controlled experiments, we show that Amphiprion ocellaris acclimated successfully to their natural host anemone species Stichodactyla gigantea, and also to Stichodactyla haddoni, and in some cases Heteractis crispa, neither of which are natural host species. No symbiosis was observed for three other anemone species tested, Entacmaea quadricolor, Macrodactyla doreensis, and Heteractis malu. We explored the skin mucous protein profile from naive and experienced A. ocellaris during their acclimation to natural and unnatural host anemones. We confidently report the presence of metabolic and structural proteins in the skin mucus of all samples, likely involved in immunological defense, molecular transport, stress response, and signal transduction. For those anemonefish that established symbiosis, there was a clear increase in ribosomal-type proteins. We additionally provide evidence for the presence of anemone proteins only in the skin mucus of individuals that established symbiosis. Our results support previous speculation of the role of skin mucous-associated proteins in anemonefish-anemone symbiosis. Further exploration of these mucosal proteins could reveal the mechanism of anemonefish acclimation to host anemones.

Redox balance and immunity of piglets pre- and post-E. coli challenge after treatment with hemp or fish oil, and vitamin E

This study investigated the influence of polyunsaturated fatty acid composition and vitamin E supplementation on oxidative status and immune responses in weanling piglets pre- and post-E. coli challenge. Suckling piglets (n = 24) were randomly selected from two litters for an oral supplementation (1 mL/day) with fish oil or hemp oil and vitamin E supplementation (60 mg natural vitamin E/mL oil) from day 10 to 28 of age. At day 29 and 30 of age, each piglet was orally inoculated with 6.7 × 108 and 3.96 × 108 CFU of F4 and F18 E. coli, respectively. Blood was sampled from all piglets on day 28 before E. coli challenge and on day 35 of age to investigate immunological and oxidative stress markers in plasma. One week after weaning and exposure to E. coli, a general reduction in the α-tocopherol concentration and activity of GPX1 was obtained. Vitamin E supplementation lowered the extent of lipid peroxidation and improved the antioxidative status and immune responses after E. coli challenge. Hemp oil had the greatest effect on antioxidant enzyme activity. Provision of hemp oil and vitamin E to suckling piglets may reduce the incidence of post-weaning diarrhea.

Growth performance, health status and flesh quality of striped catfish (Pangasianodon hypophthalmus) reared in variable stocking densities in biofloc system

Optimization of ideal stocking density in intensive aquaculture system is a challenging appraisal. Higher stocking density is inducing chronic stress, impacting negatively on physiology and increasing disease associated risks in fish. Hence, the study was designed to evaluate the water quality, growth performance, health status and flesh quality of striped catfish (Pangasianodon hypophthalmus). The fish (2.61–2.64 ± 0.01 g initial body weight) were reared in randomly designed variable stocking densities (SDs) including five treatments (30, 40, 50, 60 and 70 fish m−3) in triplicates at C:N ratio 15:1 in jaggery supplemented biofloc system for 120 days in 1000 –L experimental fiber-reinforced plastic tanks. SD30 acted as control treatment having low stocking density. During the culture, pH, alkalinity and dissolved oxygen level decreased and BOD increased with increased stocking density. TDS and TSS level increased upto SD50 treatment and further decreased in higher stocking density treatments. Higher population of heterotrophic, ammonifying and nitrifying bacteria significantly (p < 0.05) reduced TAN, NH3-N, NO2-N, and elevated NO3-Nas well as rate and potential of ammonification and nitrification in SD50 treatment than other treatments. Bacillariophyceae and protozoa were most dominant group in the biofloc microbiome in all the treatments. Highly elevated biofloc volume, floc microbiome, good floc characteristics and floc quality might have enhanced fish survival rate, body weight gain, SGR through improving FCR in SD50 than other SDs. Moreover, higher population of gut microbiota (TPC and probiotic) and elevated digestive enzymes activity in fish reared in SD50 treatment significantly (p < 0.05) enhanced PER, ANPU, and somatic indices (GSI and HSI) as well as enhanced colour (lightness, yellowness/blueness and whiteness), flesh quality and hardness. Fish reared in SD50 treatment showed significantly (p < 0.05) higher haematological (TEC, TLC and Hb), immunological (TSP, albumin, RBA and lysozyme), antioxidant responses (higher SOD and CAT) and lower metabolic stress enzymes responses (ALT, AST and glucose). Moreover, fish reared in SD50 treatment showed improved villi surface area and height in intestine and slightly vacuolated hepatocytes in liver. Overall, significantly (p < 0.05) better water quality, fish performance, health status and flesh quality were observed in SD50. Collectively, the findings suggest that farmers can be benefitted by fetching higher production through suitable stocking density (50fish m−3) of P. hypophthalmus in biofloc with improved water quality, growth performance, health status and flesh quality.

Arginine alleviates Clostridium perfringens α toxin-induced intestinal injury in vivo and in vitro via the SLC38A9/mTORC1 pathway.

Clostridium perfringens α toxin is a main virulence factor responsible for gut damage in animals. Arginine is a functional amino acid exhibiting significant immunoregulatory activities. However, the effects and immunoregulatory mechanisms of arginine supplementation on α toxin-induced intestinal injury remain unclear. In vivo, 256 male Arbor Acres chickens were randomly assigned to a 2×2 factorial arrangement, involving diet treatments (with or without 0.3% arginine supplementation) and immunological stress (with or without α toxin challenge). In vitro, IEC-6 cells were treated with or without arginine in the presence or absence of α toxin. Moreover, IEC-6 cells were transfected with siRNA targeting mTOR and SLC38A9 to explore the underlying mechanisms. The results showed that in vivo, arginine supplementation significantly alleviated the α toxin-induced growth performance impairment, decreases in serum immunoglobulin (Ig)A and IgG levels, and intestinal morphology damage. Arginine supplementation also significantly reduced the α toxin-induced increase in jejunal proinflammatory cytokines interleukin (IL)-1β, IL-6 and IL-17 mRNA expression. Clostridium perfringens α toxin significantly decreased jejunal mechanistic target of rapamycin (mTOR) and solute carrier family 38 member 9 (SLC38A9) mRNA expression, while arginine supplementation significantly increased mTOR and SLC38A9 mRNA expression. In vitro, arginine pretreatment mitigated the α toxin-induced decrease in cell viability and the increase in cytotoxicity and apoptosis. Arginine pretreatment also alleviated the α toxin-induced upregulation of mRNA expression of inflammation-related cytokines IL-6, C-X-C motif chemokine ligand (CXCL)10, CXCL11 and transforming growth factor-β (TGF-β), as well as apoptosis-related genes B-cell lymphoma-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-extra large (Bcl-XL) and cysteinyl aspartate specific proteinase 3 (Caspase-3) and the ratio of Bax to Bcl-2. Arginine pretreatment significantly increased the α toxin-induced decrease in mTOR, SLC38A9, eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1) and ribosomal protein S6 kinase (S6K) mRNA expression. Knockdown SLC38A9 and mTOR largely abrogated the positive effects of arginine pretreatment on α toxin-induced intracellular changes. Furthermore, SLC38A9 silencing abolished the increased mTOR mRNA expression caused by arginine pretreatment. In conclusion, arginine administration attenuated α toxin-induced intestinal injury in vivo and in vitro, which could be associated with the downregulation of inflammation via regulating SLC38A9/mTORC1 pathway.

Effect of an immune challenge and two feed supplements on broiler chicken individual breast muscle protein synthesis rate

Optimization of broiler chicken breast muscle protein accretion is key for the efficient production of poultry meat, whose demand is steadily increasing. In a context where antimicrobial growth promoters use is being restricted, it is important to find alternatives as well as to characterize the effect of immunological stress on broiler chicken's growth. Despite its importance, research on broiler chicken muscle protein dynamics has mostly been limited to the study of mixed protein turnover. The present study aims to characterize the effect of a bacterial challenge and the feed supplementation of citrus and cucumber extracts on broiler chicken individual breast muscle proteins fractional synthesis rates (FSR) using a recently developed dynamic proteomics pipeline. Twenty-one day-old broiler chickens were administered a single 2H2O dose before being culled at different timepoints. A total of 60 breast muscle protein extracts from five experimental groups (Unchallenged, Challenged, Control Diet, Diet 1 and Diet 2) were analysed using a DDA proteomics approach. Proteomics data was filtered in order to reliably calculate multiple proteins FSR making use of a newly developed bioinformatics pipeline. Broiler breast muscle proteins FSR uniformly decreased following a bacterial challenge, this change was judged significant for 15 individual proteins, the two major functional clusters identified as well as for mixed breast muscle protein. Citrus or cucumber extract feed supplementation did not show any effect on the breast muscle protein FSR of immunologically challenged broilers. The present study has identified potential predictive markers of breast muscle growth and provided new information on broiler chicken breast muscle protein synthesis which could be essential for improving the efficiency of broiler chicken meat production. SignificanceThe present study constitutes the first dynamic proteomics study conducted in a farm animal species which has characterized FSR in a large number of proteins, establishing a precedent for biomarker discovery and assessment of health and growth status. Moreover, it has been evidenced that the decrease in broiler chicken breast muscle protein following an immune challenge is a coordinated event which seems to be the main cause of the decreased growth observed in these animals.

AhR Activation Ameliorates Intestinal Barrier Damage in Immunostressed Piglets by Regulating Intestinal Flora and Its Metabolism.

The primary factor leading to elevated rates of diarrhea and decreased performance in piglets is immunological stress. The regulation of immune stress through the intestinal flora is a crucial mechanism to consider. In total, 30 weaned piglets were randomly allocated to five groups: the basal diet group (Control), basal diet + lipopolysaccharides group (LPS), basal diet + 250 μg/kg 6-Formylindolo [3,2-b] carbazole + LPS group (FICZ), basal diet + 3mg/kg Cardamonin + LPS group (LCDN), and basal diet + 6mg/kg Cardamonin + LPS group (HCDN/CDN). The results showed that compared with those of the LPS group, the expression of tight junction proteins (occludin; claudin-1) in the FICZ group was significantly increased, and the mRNA levels of IL-1β and TNF-α were significantly reduced (p < 0.05). HCDN treatment had a better effect on LPS-induced intestinal barrier damage in this group than it did in the LCDN group. HCDN treatment leads to a higher villus height (VH), a higher ratio of villi height to crypt depth (V/C), higher tight junction proteins (ZO-1; occludin), and higher short-chain fatty acids (SCFAs). In addition, correlation analyses showed that Succinivibrio was positively correlated with several SCFAs and negatively correlated with prostaglandin-related derivatives in the FICZ group and CDN group (p < 0.05). In summary, Cardamonin alleviates intestinal mucosal barrier damage and inflammatory responses by regulating the intestinal microbiota and its metabolism.

Effect of Caffeine on the Inflammatory-Dependent Changes in the GnRH/LH Secretion in a Female Sheep Model.

Caffeine is one of the most widely consumed psychoactive drugs in the world. It easily crosses the blood-brain barrier, and caffeine-interacting adenosine and ryanodine receptors are distributed in various areas of the brain, including the hypothalamus and pituitary. Caffeine intake may have an impact on reproductive and immune function. Therefore, in the present study performed on the ewe model, we decided to investigate the effect of peripheral administration of caffeine (30 mg/kg) on the secretory activity of the hypothalamic-pituitary unit which regulates the reproductive function in females during both a physiological state and an immune/inflammatory challenge induced by lipopolysaccharide (LPS; 400 ng/kg) injection. It was found that caffeine stimulated (p < 0.01) the biosynthesis of gonadotropin-releasing hormone (GnRH) in the hypothalamus of ewe under both physiological and inflammatory conditions. Caffeine also increased (p < 0.05) luteinizing hormone (LH) secretion in ewes in a physiological state; however, a single administration of caffeine failed to completely release the LH secretion from the inhibitory influence of inflammation. This could result from the decreased expression of GnRHR in the pituitary and it may also be associated with the changes in the concentration of neurotransmitters in the median eminence (ME) where GnRH neuron terminals are located. Caffeine and LPS increased (p < 0.05) dopamine in the ME which may explain the inhibition of GnRH release. Caffeine treatment also increased (p < 0.01) cortisol release, and this stimulatory effect was particularly evident in sheep under immunological stress. Our studies suggest that caffeine affects the secretory activity of the hypothalamic-pituitary unit, although its effect appears to be partially dependent on the animal's immune status.

CD14 down-modulation as a real-time biomarker in Kawasaki disease.

The objectives of this study were to investigate the pathophysiology of Kawasaki disease (KD) from immunological and oxidative stress perspectives, and to identify real-time biomarkers linked to innate immunity and oxidative stress in KD. We prospectively enrolled 85 patients with KD and 135 patients with diverse conditions including immune, infectious and non-infectious diseases for this investigation. Flow cytometry was used to analyse the surface expression of CD14, CD38 and CD62L on monocytes, along with a quantitative assessment of CD14down-modulation. Additionally, oxidative stress levels wereevaluated using derivatives of reactive oxygen metabolites (d-ROMs) and antioxidant capacity measured by a free radical elective evaluator system. During the acute phase of KD, we observed a prominent CD14 down-modulation on monocytes, reflecting the indirect detection of circulating innate immune molecular patterns. Moreover, patients with KD showed a significantly higher CD14 down-modulation compared with infectious and non-infectious disease controls. Notably, the surface expression of CD14 on monocytes was restored concurrently withresponses to intravenous immunoglobulin and infliximab treatment in KD. Furthermore, d-ROM levels in patients with KD were significantly elevated compared with patients with infectiousand non-infectious diseases. Following intravenous immunoglobulin treatment, oxidative stress levels decreased in patients with KD. Monitoring CD14 down-modulation on monocytes in real-time is a valuable strategy for assessing treatment response, distinguishing KD relapse from concomitant infections and selecting second-line therapy after IVIG treatment in KD patients. The interplay between inflammation and oxidative stress likely plays a crucial role in the development of KD.