课程文献中心 更多>>

关键词： Limosilactobacillus reuteri   intestinal barrier   inflammation   gut microbiota   oxidative stress   IL-17  

摘要： Limosilactobacillus reuteri, a recognized probiotic, improves intestinal health in animals, but the mechanism remains unclear. This study investigates the mechanisms by which L. reuteri ZY15, isolated from healthy pig feces, mitigates intestinal barrier damage and inflammation caused by oxidative stress in Enterotoxigenic Escherichia coli (ETEC) K88-challenged mice. The results indicated that L. reuteri ZY15 increased antioxidant capacity by reducing serum reactive oxygen species (ROS) and superoxide dismutase (SOD) levels. L. reuteri ZY15 enhanced the intestinal barrier by upregulating mucin 1, mucin 2, occludin, zonula occludens-1 (ZO-1), and claudin-1 expressions in protein and mRNA levels. It significantly alleviated intestinal inflammation by reducing the proinflammatory cytokines interleukin-1 beta (IL-1 beta), interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-17 (IL-17) mRNA and protein levels. Notably, L. reuteri ZY15 suppressed intestinal inflammation by inhibiting AKT/mTOR/HIF-1 alpha/ROR gamma t/IL-17 pathway activation. Additionally, it significantly altered the structure of gut microorganisms by enriching Akkermansia and Clostridia_UCG.014, and thereby re-establishing colonization resistance and alleviating ETEC K88-induced intestinal barrier damage and inflammation in mice. Taken together, our findings reveal the protective mechanism of L. reuteri ZY15 in mice challenged with ETEC K88 by regulating AKT/mTOR/HIF-1 alpha/ROR gamma t/IL-17 signaling and microbial imbalance. Leveraging these properties, live L. reuteri ZY15 offers a promising alternative treatment for Escherichia coli-induced diarrhea in weaned piglets.

关键词： HLA-C*01:250   novel allele   sequencing-based typing  

摘要： The HLA-C*01:250 allele differs from HLA-C*01:02:01:01 by a single non-synonymous nucleotide change in exon 7.

关键词： CPP   cell-penetrating peptide   IL   interleukin   ILC2   type 2 innate lymphoid cell  

关键词： HLA-B*52:130   NGS HLA typing novel   novel HLA-B allele  

摘要： The new HLA-B*52:130 allele showed one nonsynonymous nucleotide difference compared to the HLA-B*52:01:01:01 allele in codon 170.

关键词： HLA   HLA-DQA1   nanotype sequencing   novel allele   sequencing-based typing  

摘要： The novel allele HLA-DQA1*02:39 differs from HLA-DQA1*02:01:01:01 by one non-synonymous nucleotide substitution in exon 2.

关键词： acute kidney injury   Chenopodium botrys   inflammation   rhabdomyolysis  

摘要： Due to the anti-inflammatory and antioxidant properties of the Chenopodium botrys and the pathological mechanisms of rhabdomyolysis in the kidney, this plant can be used to improve the symptoms of this disease. Then, in this study, we investigated the effects of this herb in improving kidney injury by rhabdomyolysis. Animals were divided into five groups: control, glycerol (received it for rhabdomyolysis induction), extract (received 12 mg/kg C. botrys extract), and treatment groups with dexamethasone (0.03 mg/kg) and extract (12 mg/kg). The extract was analyzed using HNMR. After a week, blood and urine samples were taken to measure protein, urea, and creatinine. Then, the animals were sacrificed, and the kidney tissue was removed to examine the antioxidant, TNF-alpha, and histopathological evaluations. Also, NF-kappa B gene expression was investigated. The serum creatinine, TNF-alpha, and NF-kappa B ratio significantly increased and antioxidant capacity decreased in the glycerol group compared with the control. Pathological evaluation also showed severe renal damage based on the related criteria. In the treatment groups with dexamethasone and especially extract, the considered parameters attenuated relatively compared with the glycerol group. Kidney damage and functional impairment associated with rhabdomyolysis, as well as the inflammatory response caused by increased NF-kappa B and the proinflammatory cytokine TNF-alpha, may be alleviated by C. botrys. Consequently, C. botrys could represent a potential therapeutic approach for patients with rhabdomyolysis-induced acute kidney injury.

关键词： IL1-beta   inflammation   leukocyte trafficking   monocyte  

摘要： IL1-beta plays a central role in inflammation but its biological action needs to be tightly controlled. Such negative regulation can be exerted by the decoy receptor IL1R2. However, IL1R2 biology in immune cells remains poorly characterized, in particular in monocytes. Using conditional deficient mice, we show that Il1r2 deficiency in monocytes does not affect their steady-state life cycle but dysregulates their trafficking to inflamed tissues in models of peritonitis and neuro-inflammation. Mechanistically, we found that Il1r2 deficiency in monocytes increases CCL2 secretion in the inflamed peritoneum, thereby amplifying monocyte recruitment from blood. In autoimmune neuro-inflammation, Il1r2 deficiency in monocytes exacerbates disease severity. Our findings suggest that the specific action of IL1R2 in monocytes contributes to a feedback mechanism for fine-tuning the numbers of recruited monocytes during inflammation.

关键词： CD4(+) T cell differentiation   hereditary vitamin D-resistant rickets   retinoic acid   retinoic acid receptor   retinoid X receptor   vitamin D   vitamin D receptor  

摘要： The effects of vitamin D and vitamin A in immune cells are mediated through the vitamin D receptor (VDR) and retinoic acid receptor (RAR), respectively. These receptors share the retinoid X receptor (RXR) co-factor for transcriptional regulation. We investigated the effects of active vitamin D-3 (1,25(OH)(2)D-3) and 9-cis retinoic acid (9cRA) on T helper (T-H)1 and T(H)2 cytokines and transcription factors in primary human blood-derived CD4(+) T cells. We aimed to address the discrepancies in this field, particularly regarding the effects of 9cRA and the vitamins in combination. 1,25(OH)(2)D-3 upregulated IL-13 and suppressed IFN gamma, while 9cRA had the opposite effects. This was largely independent of a T(H)1/T(H)2 phenotype shift. Combined vitamin supplementation produced intermediate cytokine levels, not only through transcriptional regulation by VDR-RXR and RAR-RXR but also through 1,25(OH)(2)D-3 counteracting the effects of 9cRA on solely 9cRA-responsive genes. Similar results were observed in hereditary vitamin D-resistant rickets (HVDRR) patient T cells, where VDR cannot bind to DNA, indicating that RXR binding to either receptor can limit the other's activity. Additionally, we observed downregulated RAR upon 9cRA supplementation and its re-localization out of the nucleus upon 1,25(OH)(2)D-3 supplementation, suggesting a mechanism of indirect regulation by VDR. VDR protein levels were also upregulated upon 9cRA supplementation, suggesting a novel negative feedback mechanism of 9cRA transcriptional activity, whereby 9cRA promotes its own competitor. This study sets the stage for future research into the combined immunomodulatory mechanisms of 1,25(OH)(2)D-3 and 9cRA, involving both direct transcriptional regulation and indirect regulation via RXR competitive binding.