Biomarkers of oxidative stress in broiler chickens attacked by lipopolysaccharide: A systematic review and meta-analysis.

Oxidative stress (OS) constitutes a pivotal factor in the initiation and progression of lipopolysaccharide (LPS) challenges in broiler chickens. Increasing studies have demonstrated that Alleviation of oxidative stress seems to be a reasonable strategy to alleviate LPS-mediated afflictions in broilers. Nonetheless, the relationship between OS-related indicators and exposure to LPS remains a topic of debate. The aim of this investigation was to precisely and holistically evaluate the effect of LPS exposure on OS-associated markers. We conducted a systematic search of four electronic databases-PubMed, Web of Science, Scopus, and Cochrane for relevant studies, and a total of 31 studies were included. The overall results showed that the LPS treatment significantly increased the levels of oxygen radicals and their products, such as malondialdehydes (MDA), reactive oxygen species (ROS), and 8-hydroxy-2-deoxyguanosine (8-OHdG), while significantly reduced the levels of antioxidants, such as total antioxidative capacity (T-AOC), total superoxide dismutase (T-SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione (GSH), in the chickens. Intriguingly, though the observed trends in alterations were not strictly correlated with LPS concentrations, the enzyme activity levels were indeed influenced by the concentration of LPS. This observation highlights the complex relationship between LPS exposure and the body's antioxidant response. Despite some limitations, all the included studies were deemed credible. Subgroup evaluations revealed that the jejunum and duodenum has demonstrated stronger antioxidant capability compared to other tissues. Overall, our study presents compelling evidence that exposure to LPS induces significant OS in chickens. And we also found that the extent of OS was related to LPS doses, target tissues, and dietary ingredients.

Changed cecal microbiota involved in growth depression of broiler chickens induced by immune stress.

A previous study identified genes and metabolites associated with amino acid metabolism, glycerophospholipid metabolism, and inflammatory response in the liver of broilers with immune stress. The present research was designed to investigate the effect of immune stress on the cecal microbiome in broilers. In addition, the correlation between altered microbiota and liver gene expression, the correlation between altered microbiota and serum metabolites were compared using the Spearman correlation coefficients. Eighty broiler chicks were randomly assigned to 2 groups with 4 replicate pens per group and 10 birds per pen. The model broilers were intraperitoneally injected of 250 µg/kg LPS at 12, 14, 33, and 35 d of age to induce immunological stress. Cecal contents were taken after the experiment and kept at -80°C for 16S rDNA gene sequencing. Then the Pearson's correlation between gut microbiome and liver transcriptome, between gut microbiome and serum metabolites were calculated using R software. The results showed that immune stress significantly changed microbiota composition at different taxonomic levels. KEGG pathways analysis suggested that these gut microbiota were mainly involved in biosynthesis of ansamycins, glycan degradation, D-glutamine and D-glutamate metabolism, valine, leucine, and isoleucine biosynthesis and biosynthesis of vancomycin group antibiotics. Moreover, immune stress increased the activities of metabolism of cofactors and vitamins, as well as decreased the ability of energy metabolism and digestive system. Pearson's correlation analysis identified several bacteria were positively correlated with the gene expression while a few of bacteria were negatively correlated with the gene expression. The results identified potential microbiota involvement in growth depression mediated by immune stress and provided strategies such as supplement of probiotic for alleviating immune stress in broiler chickens.

Ginsenoside Rg1 and Re alleviates inflammatory responses and oxidative stress of broiler chicks challenged by lipopolysaccharide.

Previous study showed that ginsenoside Rg1 (Rg1) and ginsenoside Re (Re) alleviated growth inhibition of broiler chicks with immune stress. The aim of this study was to investigate the effect of Rg1 and Re on inflammatory responses, oxidative stress, and apoptosis in liver of broilers with immune stress induced by lipopolysaccharide (LPS). Forty broiler chicks were randomly divided into 4 groups, each group consisting of 10 chickens. The model group, Rg1 group, and Re group were received continuously interval injection of 250 µg/kg body weight LPS at the age of 12, 14, 33, and 35 days to induce immune stress. Control group was injected with an equivalent amount of sterile saline. Then broilers in Rg1 group and Re group were given 1mg/kg body weight Rg1 and Re intraperitoneally 2 h after the LPS challenge respectively. Blood samples were collected for the detection of hormone levels, inflammatory mediators, and antioxidant parameters. Hepatic tissues were taken for pathological observation. Total RNA was extracted from the liver for real-time quantitative polymerase chain reaction analysis. Our results showed that Rg1 or Re could alleviate histological changes of liver, reduce production of stress-related hormones, inhibit inflammatory responses, and enhance antioxidant capacity in broilers challenged by immune stress. In addition, Rg1 or Re treatment upregulated mRNA expression of antioxidant-related genes and downregulated mRNA expression of inflammation-related factors and apoptosis-related genes in the liver of immune-stressed broilers. The results suggest that the plant extracts containing Rg1 and Re can be used for ameliorating hepatic oxidative stress and inflammation and controlling immune stress in broiler chicks.

Glutamine is essential for overcoming the immunosuppressive microenvironment in malignant salivary gland tumors.

Rationale: Immunosuppression in the tumor microenvironment (TME) is key to the pathogenesis of solid tumors. Tumor cell-intrinsic autophagy is critical for sustaining both tumor cell metabolism and survival. However, the role of autophagy in the host immune system that allows cancer cells to escape immune destruction remains poorly understood. Here, we determined if attenuated host autophagy is sufficient to induce tumor rejection through reinforced adaptive immunity. Furthermore, we determined whether dietary glutamine supplementation, mimicking attenuated host autophagy, is capable of promoting antitumor immunity. Methods: A syngeneic orthotopic tumor model in Atg5+/+ and Atg5flox/flox mice was established to determine the impact of host autophagy on the antitumor effects against mouse malignant salivary gland tumors (MSTs). Multiple cohorts of immunocompetent mice were used for oncoimmunology studies, including inflammatory cytokine levels, macrophage, CD4+, and CD8+ cells tumor infiltration at 14 days and 28 days after MST inoculation. In vitro differentiation and in vivo dietary glutamine supplementation were used to assess the effects of glutamine on Treg differentiation and tumor expansion. Results: We showed that mice deficient in the essential autophagy gene, Atg5, rejected orthotopic allografts of isogenic MST cells. An enhanced antitumor immune response evidenced by reduction of both M1 and M2 macrophages, increased infiltration of CD8+ T cells, elevated IFN-γ production, as well as decreased inhibitory Tregs within TME and spleens of tumor-bearing Atg5flox/flox mice. Mechanistically, ATG5 deficiency increased glutamine level in tumors. We further demonstrated that dietary glutamine supplementation partially increased glutamine levels and restored potent antitumor responses in Atg5+/+ mice. Conclusions: Dietary glutamine supplementation exposes a previously undefined difference in plasticity between cancer cells, cytotoxic CD8+ T cells and Tregs.

Two-carbon folate cycle of commensal Lactobacillus reuteri 6475 gives rise to immunomodulatory ethionine, a source for histone ethylation.

Colonization of the gut by certain probiotic Lactobacillus reuteri strains has been associated with reduced risk of inflammatory diseases and colorectal cancer. Previous studies pointed to a functional link between immunomodulation, histamine production, and folate metabolism, the central 1-carbon pathway for the transfer of methyl groups. Using mass spectrometry and NMR spectroscopy, we analyzed folate metabolites of L. reuteri strain 6475 and discovered that the bacterium produces a 2-carbon-transporting folate in the form of 5,10-ethenyl-tetrahydrofolyl polyglutamate. Isotopic labeling permitted us to trace the source of the 2-carbon unit back to acetate of the culture medium. We show that the 2C folate cycle of L. reuteri is capable of transferring 2 carbon atoms to homocysteine to generate the unconventional amino acid ethionine, a known immunomodulator. When we treated monocytic THP-1 cells with ethionine, their transcription of TNF-α was inhibited and cell proliferation reduced. Mass spectrometry of THP-1 histones revealed incorporation of ethionine instead of methionine into proteins, a reduction of histone-methylation, and ethylation of histone lysine residues. Our findings suggest that the microbiome can expose the host to ethionine through a novel 2-carbon transporting variant of the folate cycle and modify human chromatin via ethylation.-Röth, D., Chiang, A. J., Hu, W., Gugiu, G. B., Morra, C. N., Versalovic, J., Kalkum, M. The two-carbon folate cycle of commensal Lactobacillus reuteri 6475 gives rise to immunomodulatory ethionine, a source for histone ethylation.

Role of lateral hypothalamus in two aspects of attention in associative learning.

Orexin (hypocretin) and melanin-concentrating hormone (MCH) neurons are unique to the lateral hypothalamic (LH) region, but project throughout the brain. These cell groups have been implicated in a variety of functions, including reward learning, responses to stimulants, and the modulation of attention, arousal and the sleep/wakefulness cycle. Here, we examined roles for LH in two aspects of attention in associative learning shown previously to depend on intact function in major targets of orexin and MCH neurons. In experiments 1 and 2, unilateral orexin-saporin lesions of LH impaired the acquisition of conditioned orienting responses (ORs) and bilaterally suppressed FOS expression in the amygdala central nucleus (CeA) normally observed in response to food cues that provoke conditioned ORs. Those cues also induced greater FOS expression than control cues in LH orexin neurons, but not in MCH neurons. In experiment 3, unilateral orexin-saporin lesions of LH eliminated the cue associability enhancements normally produced by the surprising omission of an expected event. The magnitude of that impairment was positively correlated with the amount of LH damage and with the loss of orexin neurons in particular, but not with the loss of MCH neurons. We suggest that the effects of the LH orexin-saporin lesions were mediated by their effect on information processing in the CeA, known to be critical to both behavioral phenomena examined here. The results imply close relations between LH motivational amplification functions and attention, and may inform our understanding of disorders in which motivational and attentional impairments co-occur.

Magnesium lithospermate B protects neurons from N-methyl-D-aspartic acid injury and attenuates kainic acid-induced neurodegeration in FVB mice.

Magnesium lithospermate B (MLB) is one of the major bioactive components of Radix Salviae miltiorrhizae (Dan Shen), which is a Chinese traditional herbal medicine with therapeutic effects on cardiovascular and cerebrovascular diseases. The aim of this study was to investigate the neuroprotective effects of MLB on N-methyl-D-aspartic acid (NMDA)-injured neurons and against kainic acid (KA)-induced neurodegeneration in mice. In cultured mouse primary hippocampal neurons, MLB significantly reduced NMDA-induced cell death and promoted neurite growth in a dose-dependent manner. In FVB mice, MLB attenuated KA-induced neurodegeneration. Additionally, MLB prevented the decrease in phosphorylated Akt and glycogen synthase kinase-3ß (GSK-3ß) levels both in NMDA-injured neurons and KA-injured mouse brain. This effect was blocked by phosphoinositide 3-kinase (PI3K) inhibitor LY294002 and Akt inhibitor triciribine, thus indicating the neuroprotective effects of MLB are most likely mediated by the PI3K/Akt/GSK-3ß pathway. Taken together, these results show the efficacy and underlying mechanism of MLB against neuronal injury and raise its therapeutic potential in neurodegenerative diseases.

Age-dependent effects of testosterone in experimental stroke.

Although male sex is a well-recognized risk factor for stroke, the role of androgens in cerebral ischemia remains unclear. Therefore, we evaluated effects of testosterone on infarct size in both young adult and middle-aged rats (Wistar, 3-month versus 14-month old) and mice (C57/BL6, 3-month versus 12-month old) subjected to middle cerebral artery occlusion. In young adult groups, castrates displayed less ischemic damage as compared with intact males and castrates with testosterone replacement (Cortex: 24% in castrates versus 42% in intact versus 40% with testosterone; Striatum: 45% versus 73% versus 70%) at 22 h reperfusion. Surprisingly, supplementing testosterone in middle-aged rats to the physiologic levels ordinarily seen in young males reduced infarction (Cortex: 2% with testosterone versus 31%; Striatum: 38% with testosterone versus 68%). Testosterone effects on infarct size were blocked by the androgen receptor (AR) antagonist flutamide and further confirmed in young versus middle-aged mice. Baseline cerebral aromatase mRNA levels and activity were not different between young and middle-aged rats. Aromatase activity increased in ischemic tissue, but only in young males. Lastly, stroke damage was not different in aging aromatase knockout mice versus wild-type controls. Our findings indicate that testosterone's effects in experimental stroke are age dependent, mediated via AR, but not cerebral aromatase.