Treatment with onion bulb extract both prevents and reverses allergic inflammation in a murine model of asthma.

CONTEXT: Asthma presents a global health challenge. The main pharmacotherapy is synthetic chemicals and biological-based drugs that are costly, and have significant side effects. In contrast, use of natural products, such as onion (Allium cepa L., Amaryllidaceae) in the treatment of airway diseases has increased world-wide because of their perceived efficacy and little safety concerns. However, their pharmacological actions remain largely uncharacterized. OBJECTIVE: We investigated whether onion bulb extract (OBE) can (1) reverse established asthma phenotype (therapeutic treatment) and/or (2) prevent the development of the asthma phenotype, if given before the immunization process (preventative treatment). MATERIALS AND METHODS: Six groups of male Balb/c mice were established for the therapeutic (21 days) and five groups for the preventative (19 days) treatment protocols; including PBS and house dust mite (HDM)-challenged mice treated with vehicle or OBE (30, 60, and 100 mg/kg/i.p.). Airways inflammation was determined using cytology, histology, immunofluorescence, Western blot, and serum IgE. RESULTS: Therapeutic (60 mg/kg/i.p.) and preventative (100 mg/kg/i.p.) OBE treatment resulted in down-regulation of HDM-induced airway cellular influx, histopathological changes and the increase in expression of pro-inflammatory signaling pathway EGFR, ERK1/2, AKT, pro-inflammatory cytokines and serum IgE. DISCUSSION AND CONCLUSION: Our data show that OBE is an effective anti-inflammatory agent with both therapeutic and preventative anti-asthma effects. These findings imply that onion/OBE may be used as an adjunct therapeutic agent in established asthma and/or to prevent development of allergic asthma. However, further studies to identify the active constituents, and demonstrate proof-of-concept in humans are needed.

Diosgenin protects against cationic bovine serum albumin-induced membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway.

CONTEXT: Membranous glomerulonephritis (MGN) is a leading cause of nephrotic syndrome in adults. Diosgenin (DG) has been reported to exert antioxidative and anti-inflammatory effects. OBJECTIVE: To investigate the renoprotective activity of DG in a cationic bovine serum albumin-induced rat model of MGN. MATERIALS AND METHODS: Fourty male Sprague-Dawley rats were randomized into four groups. The MGN model was established and treated with a DG dose (10 mg/kg) and a positive control (TPCA1, 10 mg/kg), while normal control and MGN groups received distilled water by gavage for four consecutive weeks. At the end of the experiment, 24 h urinary protein, biochemical indices, oxidation and antioxidant levels, inflammatory parameters, histopathological examination, immunohistochemistry and immunoblotting were evaluated. RESULTS: DG significantly ameliorated kidney dysfunction by decreasing urinary protein (0.56-fold), serum creatinine (SCr) (0.78-fold), BUN (0.71-fold), TC (0.66-fold) and TG (0.73-fold) levels, and increasing ALB (1.44-fold). DG also reduced MDA (0.82-fold) and NO (0.83-fold) levels while increasing the activity of SOD (1.56-fold), CAT (1.25-fold), glutathione peroxidase (GPx) (1.55-fold) and GSH (1.81-fold). Furthermore, DG reduced Keap1 (0.76-fold) expression, Nrf2 nuclear translocation (0.79-fold), and induced NQO1 (1.25-fold) and HO-1 (1.46-fold) expression. Additionally, DG decreased IL-2 (0.55-fold), TNF-α (0.80-fold) and IL-6 (0.75-fold) levels, and reduced protein expression of NF-κB p65 (0.80-fold), IKKß (0.93-fold), p-IKKß (0.89-fold), ICAM-1 (0.88-fold), VCAM-1 (0.91-fold), MCP-1 (0.88-fold) and E-selectin (0.87-fold), and also inhibited the nuclear translocation of NF-κB p65 (0.64-fold). DISCUSSION AND CONCLUSIONS: The results suggest a potential therapeutic benefit of DG against MGN due to the inhibition of the NF-κB pathway, supporting the need for further clinical trials.

Acanthopanax senticosus cultures fermented by Lactobacillus rhamnosus enhanced immune response through improvement of antioxidant activity and inflammation in crucian carp (Carassius auratus).

Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.

Saponins from Allium macrostemon Bulbs Attenuate Endothelial Inflammation and Acute Lung Injury via the NF-κB/VCAM-1 Pathway.

Endothelial inflammation is a multifaceted physiological process that plays a pivotal role in the pathogenesis and progression of diverse diseases, encompassing but not limited to acute lung infections like COVID-19, coronary artery disease, stroke, sepsis, metabolic syndrome, certain malignancies, and even psychiatric disorders such as depression. This inflammatory response is characterized by augmented expression of adhesion molecules and secretion of pro-inflammatory cytokines. In this study, we discovered that saponins from Allium macrostemon bulbs (SAMB) effectively inhibited inflammation in human umbilical vein endothelial cells induced by the exogenous inflammatory mediator lipopolysaccharide or the endogenous inflammatory mediator tumor necrosis factor-α, as evidenced by a significant reduction in the expression of pro-inflammatory factors and vascular cell adhesion molecule-1 (VCAM-1) with decreased monocyte adhesion. By employing the NF-κB inhibitor BAY-117082, we demonstrated that the inhibitory effect of SAMB on VCAM-1 expression may be attributed to the NF-κB pathway's inactivation, as characterized by the suppressed IκBα degradation and NF-κB p65 phosphorylation. Subsequently, we employed a murine model of lipopolysaccharide-induced septic acute lung injury to substantiate the potential of SAMB in ameliorating endothelial inflammation and acute lung injury in vivo. These findings provide novel insight into potential preventive and therapeutic strategies for the clinical management of diseases associated with endothelial inflammation.

Effects of an artificial pancreas on postoperative inflammation in patients with esophageal cancer.

PURPOSES: Subtotal esophagectomy for esophageal cancer (EC) is associated with high morbidity rates. Tight glycemic control using an artificial pancreas (AP) is one of the promising strategies to reduce postoperative inflammation and morbidities. However, the effects of tight glycemic control using AP in patients with EC are yet to be fully elucidated. METHOD: This study reviewed 96 patients with EC who underwent subtotal esophagectomy. The postoperative inflammation parameters and morbidity rates were compared between patients who used the AP (n = 27) or not (control group, n = 69). AP is a closed-loop system that comprises a continuous glucose monitor and an insulin pump. RESULTS: The numbers of white blood cells (WBC) and Neutrophils (Neut) were noted to be lower in the AP group than in the control group, but with no significant difference. The ratio in which the number of WBC, Neut, and CRP on each postoperative day (POD) was divided by those tested preoperatively was used to standardize the results. The ratio of WBC and Neut on 1POD was significantly lower in the AP group than in the control group. The rate of surgical site infection was lower in the AP group than in the control group. CONCLUSION: AP significantly decreased WBC and Neut on 1POD; this suggests the beneficial effects of AP in alleviating postoperative inflammation.

The Potential Use of Vitamin D3 and Phytochemicals for Their Anti-Ageing Effects.

Unlike other vitamins, vitamin D3 is synthesised in skin cells in the body. Vitamin D3 has been known as a bone-related hormone. Recently, however, it has been considered as an immune vitamin. Vitamin D3 deficiency influences the onset of a variety of diseases. Vitamin D3 regulates the production of proinflammatory cytokines such as tumour necrosis factor-α (TNF-α) through binding to vitamin D receptors (VDRs) in immune cells. Since blood levels of vitamin D3 (25-OH-D3) were low in coronavirus disease 2019 (COVID-19) patients, there has been growing interest in the importance of vitamin D3 to maintaining a healthy condition. On the other hand, phytochemicals are compounds derived from plants with over 7000 varieties and have various biological activities. They mainly have health-promoting effects and are classified as terpenoids, carotenoids, flavonoids, etc. Flavonoids are known as the anti-inflammatory compounds that control TNF-α production. Chronic inflammation is induced by the continuous production of TNF-α and is the fundamental cause of diseases like obesity, dyslipidaemia, diabetes, heart and brain diseases, autoimmune diseases, Alzheimer's disease, and cancer. In addition, the ageing process is induced by chronic inflammation. This review explains the cooperative effects of vitamin D3 and phytochemicals in the suppression of inflammatory responses, how it balances the natural immune response, and its link to anti-ageing effects. In addition, vitamin D3 and phytochemicals synergistically contribute to anti-ageing by working with ageing-related genes. Furthermore, prevention of ageing processes induced by the chronic inflammation requires the maintenance of healthy gut microbiota, which is related to daily dietary habits. In this regard, supplementation of vitamin D3 and phytochemicals plays an important role. Recently, the association of the prevention of the non-disease condition called "ME-BYO" with the maintenance of a healthy condition has been an attractive regimen, and the anti-ageing effect discussed here is important for a healthy and long life.

Theacrine enhances autophagy and inhibits inflammation via regulating SIRT3/FOXO3a/Parkin pathway.

BACKGROUND: Psoriasis, a common chronic inflammatory skin condition, impacts around 2%-3% of the global population. Theacrine is recognized for its potential anti-inflammatory and antioxidant properties. However, the role of theacrine in psoriasis remains unclear. PURPOSES: To investigate the effects of theacrine on psoriasis and explore the underlying signaling pathways. METHODS: For imiquimod (IMQ)-induced Psoriasis-like mice, the psoriatic inflammation was monitored using Psoriasis Area and Severity Index (PASI). The skin damage was observed using Hematoxylin and Eosin staining. The KI67 and CD4 in skin tissues were assessed using Immunohistochemistry analysis. Western blots were performed to evaluate the expression of Keratin 1 (KRT1), KRT6, LC3, P62, Beclin1, T-bet, GATA3, RAR-related orphan receptor (ROR)-γt, Sirtuin-3 (SIRT3), Forkhead Box O3a (FOXO3a) and Parkin. Additionally, LC3B expression was analyzed using an immunofluorescent assay, while flow cytometry was performed to analyze the percentage of Th17, Th1, and Th2 positive cells in skin-draining lymph node. RESULTS: Theacrine improved skin condition by reducing hyperkeratosis and acanthosis, lowering PASI scores, and decreasing KI67-positive cells. Theacrine also modulated keratin expression, elevating KRT1 while reducing KRT6 levels. Theacrine enhanced autophagy indicated by an increased LC3-II/LC3-I ratio and Beclin1, while reduced P62 levels. Additionally, Theacrine reduced CD4-positive cells and suppressed Th17 and Th1 cell activation. Theacrine activated the FOXO3a/Parkin pathway by upregulating SIRT3 expression, and down-regulation of SIRT3 counteracted theacrine's effects in psoriasis-like mice. CONCLUSION: Theacrine inhibits skin damage, promotes autophagy, and mediates inflammation in IMQ-induced psoriasis mice via upregulating SIRT3 to activate FOXO3a/Parkin pathway, positioning theacrine as a candidate for psoriasis treatment.

Modulation of faecal miRNAs highlights the preventive effects of a Mediterranean low-inflammatory dietary intervention.

BACKGROUND: Dietary interventions have been proposed as therapeutic approaches for several diseases, including cancer. A low-inflammatory Mediterranean dietary intervention, conducted as a pilot study in subjects with Familial Adenomatous Polyposis (FAP), reduced markers of local and systemic inflammation. We aim to determine whether this diet may modulate faecal microRNA (miRNA) and gene expression in the gut. METHODS: Changes in the faecal miRNome were evaluated by small RNA sequencing at baseline (T0), after the three-month intervention (T1), and after an additional three months (T2). Changes in the transcriptome of healthy rectal mucosa and adenomas were evaluated by RNA sequencing at T0 and T2. The identification of validated miRNA-gene interactions and functional analysis of miRNA targets were performed using in silico approaches. RESULTS: Twenty-seven subjects were included in this study. It was observed that the diet modulated 29 faecal miRNAs (p < 0.01; |log2 Fold Change|>1), and this modulation persisted for three months after the intervention. Levels of miR-3612-3p and miR-941 correlated with the adherence to the diet, miR-3670 and miR-4252-5p with faecal calprotectin, and miR-3670 and miR-6867 with serum calprotectin. Seventy genes were differentially expressed between adenoma and normal tissue, and most were different before the dietary intervention but reached similar levels after the diet. Functional enrichment analysis identified the proinflammatory ERK1/2, cell cycle regulation, and nutrient response pathways as commonly regulated by the modulated miRNAs and genes. CONCLUSIONS: Faecal miRNAs modulated by the dietary intervention target genes that participate in inflammation. Changes in levels of miRNAs and genes with oncogenic and tumour suppressor functions further support the potential cancer-preventive effect of the low-inflammatory Mediterranean diet. CLINICAL TRIAL NUMBER REGISTRATION: NCT04552405, Registered in ClinicalTrials.gov.

Preventative and therapeutic potential of nutrition for inflammatory bowel diseases: A narrative review.

Diet strongly shapes the gut microbiome and metabolome, which in turn influence intestinal inflammation in patients with inflammatory bowel disease (IBD). Separate from inflammation and malnutrition, diet's direct interactions with the gastrointestinal system can also provoke or attenuate a host of nonspecific gastrointestinal symptoms. Given these multifaceted effects of diet on inflammation and symptoms, nutrition has been investigated for its potential roles in the prevention and treatment of IBD. This review presents epidemiological, observational cohort, and clinical trial evidence that underlie our current understanding of nutrition for prevention and treatment of IBD.

Preventive effects of hesperidin in an experimental model ofs acute lung inflammation.

In this study, we hypothesized that long-term administration of hesperidin can modulate the inflammatory response and oxidative stress in animals submitted to mechanical ventilation (MV). Twenty-five C57BL/6 male mice were divided into 5 groups: control, MV, animals receiving hesperidin in three doses 10, 25 and 50 mg/kg. The animals received the doses of hesperidin for 30 days via orogastric gavage, and at the end of the period the animals were submitted to MV. In animals submitted to MV, increased lymphocyte, neutrophil and monocyte/macrophage cell counts were observed in the blood and airways. Associated to this, MV promoted an increase in inflammatory cytokine levels such as CCL2, IL-12 and TNFα. The daily administration of hesperidin in the three doses prevented the effects caused by MV, which was observed by a lower influx of inflammatory cells into the airways, a reduction in inflammatory markers and less oxidative damage.

Amelioration of obesity and inflammation by polysaccharide from unripe fruits of raspberry via gut microbiota regulation.

Raspberry, a traditional medicine food homology species, has important benefits in patients with metabolic syndrome. However, the mechanism of raspberry polysaccharides (RP) on obesity remains unclear. In our study, we showed that RP intervention is negatively associated with body weight gain, hyperlipidemia, inflammation, and fat accumulation in obese mice. RP ameliorated HFD-induced gut microbiota dysbiosis, produced short-chain fatty acids, maintained intestinal barrier integrity, and prevented metabolic endotoxemia, manifested by decreased host lipopolysaccharide level, and increased colon expression of tight junction proteins. These effects might be related with driven by a SCFAs-producing bacterium and downregulation of TLR4/NF-κB signaling transduction. Notably, the abundance of Ruminococcaceae_UCG - 014, Lactobacillus taiwanensis, Bifidobacterium pseudolongum, and Turicibacter are markedly correlated with enhanced intestinal barrier function induced by RP treatment. Thus, we believe that RP could be as a potential health supplement or prebiotic for obesity therapy.

Impact of folic acid supplementation on ischemia‒reperfusion-induced kidney injury in rats: folic acid prophylactic role revisited.

Folic acid (FA), with its anti-inflammatory and antioxidant properties, may offer protection against ischemia-reperfusion (IR) injury. This study investigated whether FA safeguards rat kidneys from IR by targeting high mobility group box-1 (HMGB1), a key inflammatory mediator. Fifty adult male Wistar rats were randomly allocated into four groups: control, IR, IR + FA pretreatment, and FA alone. Compared to controls, IR significantly impaired renal function and elevated levels of malondialdehyde, HMGB1, NF-κB, and caspase 3. FA pretreatment effectively reversed these detrimental changes, protecting renal function and minimizing tissue damage. The FA-alone group showed no significant differences compared to the control group, indicating no adverse effects of FA treatment. Mechanistically, FA inhibited HMGB1 expression and its downstream activation of NF-κB and caspase 3, thereby quelling inflammation and cell death. FA shields rat kidneys from IR-induced injury by suppressing HMGB1-mediated inflammation and apoptosis, suggesting a potential therapeutic avenue for IR-associated kidney damage.

Self-assembled coating with a metal-polyphenolic network for intraocular lens modification to prevent posterior capsule opacification.

Posterior capsule opacification (PCO) is a main complication after cataract surgery and intraocular lens (IOLs) implantation and is attributed to residual lens epithelial cells (LECs) migrating to the IOL surface and posterior capsules. IOL surface modification has been a newly-developing research filed in recent years; however, the applicability and economical acquisition of modified materials remain unsolved. In this study, we first applied a metal-polyphenolic network coating with a self-assembly technique on the IOL surface by using tannic acid (TA) combined with AlCl3, which are easily acquire and applying on the IOL surface to solve the IOL transmittance affair. Using wound healing and Transwell assay to verify AZD0364 inhibits cell migration (P< 0.05), the lipopolysaccharide-induced macrophage inflammation model to verify pterostilbene (PTE) inhibits the inflammatory reaction (P< 0.01). By optimizes its self-assembly coating parameters and calculating its drug release kinetics, we successfully loaded these two drugs on the coating, named TA (AZD0364/PTE) IOL. Its surface morphology characteristics were analyzed by scanning electron microscope, x-ray photoelectron spectrometer and water contact angle. The optical performance was carefully investigated by optical instruments and equipment (n= 3). Thein vitroresults showed that TA (AZD0364/PTE) IOL can significantly inhibit cell adhesion and acute inflammation (n= 3,P< 0.0001). Importantly, afterin vivoimplantation for 28 d with eight rabbits PCO models in two groups, the TA (AZD0364/PTE) IOL group maintained clear refracting media and decreased the inflammatory reaction compared with the original IOL group (P< 0.05). This study provides a new applicable and economical strategy for preventing PCO and offers a reference for the next generation of IOLs that benefit cataract patients.

Aucubin provides protection against cerebral ischaemia-reperfusion injury by suppressing neuronal apoptosis, oxidative stress, and inflammation through the modulation of the AKT-GSK-3ß-Nrf2 signal cascade.

Aucubin (AU) is a naturally occurring iridoid glycoside known to possess a wide range of pharmacological properties and exhibit a notable protective effect against various pathological conditions. Studies have shown that AU has neuroprotective properties in different neurological diseases. However, its potential protective effects against cerebral ischemia-reperfusion (CIR) injury have not been thoroughly investigated. This study aimed to investigate the impact of AU on CIR injury and explore the underlying mechanism. Cultured neurons treated with AU showed a significant reduction in apoptosis, oxidative stress, and inflammation caused by oxygen-glucose deprivation and reoxygenation (OGD/R). In a rat model of CIR, treatment with AU resulted in a significant decrease in cerebral infarct size and neurological deficits. AU treatment also reversed the increased apoptosis, oxidative stress, and inflammation in the brains of CIR rats. Furthermore, AU was found to enhance the activation of nuclear factor-erythroid 2-related factor 2 (Nrf2), accompanied by increased phosphorylation of serine/threonine-protein kinase AKT and glycogen synthase kinase-3 beta (GSK-3ß). The activation of Nrf2 induced by AU was reversed when the AKT-GSK-3ß cascade was blocked. Additionally, the neuroprotective effect of AU was significantly reduced when Nrf2 was pharmacologically suppressed. In conclusion, these findings suggest that AU exerts a neuroprotective effect on CIR injury, and this effect is mediated by the activation of Nrf2 through the AKT-GSK-3ß axis. This work highlights the potential of AU as a drug candidate for the treatment of CIR injury.

PKR inhibitor protects spinal cord injury through mitigating endoplasmic reticulum stress and pyroptosis.

OBJECTIVES: The goal of the study was to reveal the regulatory role of protein kinase R (PKR) in spinal cord injury (SCI), a devasting disorder of the neurological system, and to elucidate its potential mechanism. METHODS: The established animal and cellular models of SCI were treated by the PKR inhibitor C12. Histological injury and tissue apoptosis were assessed via H&E staining and TUNEL assays, respectively. Basso-Beattie-Bresnahan (BBB) scoring as well as forelimb grip strength tests were employed to evaluate functional recovery. The production of ROS and cytokines were appraised via their related commercial kits. Western blot and immunofluorescence assay were used to examine protein expression. CCK-8 method was used to assay cell activity. Co-immunoprecipitation assay was conducted to measure the affinity of PKR with STAT1. RESULTS: PKR expression was enhanced following SCI, and the PKR inhibitor C16 mitigated histological injury, cell apoptosis and water content in spinal cord, and improved function recovery following SCI. Meanwhile, C16 attenuated ER stress, pyroptosis, NLRP3 inflammasome and inflammation in mice with SCI and in BV-2 cells challenged with LPS. Additionally, PKR interacted with STAT1 in BV-2 cells, and STAT1 knockdown inhibited ER stress, pyroptosis and inflammation in BV-2 cells challenged with LPS. The protective role of C16 in BV-2 cells exposed to LPS were partly abolished by STAT1 overexpression. CONCLUSION: PKR inhibition might be a prospective effective approach to attenuating SCI and accelerating function recovery through modulating microglial pyroptosis and ER stress.

Chlorogenic acid protects against intestinal inflammation and injury by inactivating the mtDNA-cGAS-STING signaling pathway in broilers under necrotic enteritis challenge.

This study aimed to determine the effects of chlorogenic acid (CGA) on the growth performance, intestinal health, immune response, and mitochondrial DNA (mtDNA)-cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway in broilers under necrotic enteritis (NE) challenge. The 180 one-day-old male Cobb 500 broilers with similar body weight of 44.59 ± 1.39 g were randomly allocated into 3 groups. The groups were control diet (Control group), control diet + NE challenge (NE group), and control diet + 500 mg/kg CGA + NE challenge (NE + CGA group), with 6 replicates per treatment. All broilers except the Control group were given sporulated coccidian oocysts (d 14) and Clostridium perfringens (d 19-21) by oral gavage. Our findings showed that CGA improved the growth performance and intestinal morphology in broilers under NE challenge. CGA supplementation elevated the barrier function in broilers under NE challenge, which reflected in the decreased serum concentrations of D-lactate and diamine oxidase, and upregulated jejunal protein expression of occludin. CGA supplementation also improved the immune function, which reflected in the increased concentrations and gene expressions of anti-inflammatory factors, and decreased concentrations and gene expressions of proinflammatory factors. CGA supplementation further enhanced intestinal cell proliferation and differentiation, which manifested in the increased number of goblet cells and positive cells of proliferating cell nuclear antigen on d 28 and 42. Furthermore, CGA supplementation decreased the mtDNA (d 42) and mitochondrial reactive oxygen species levels (d 28 and 42), and increased the mitochondrial membrane potential (d 42) and mitochondrial complex I (d 28 and 42) or III (d 28) activity. Broilers challenged with NE had upregulated jejunal protein expressions of cGAS, phospho-TANK-binding kinase 1, and phospho-interferon regulatory factor 7 compared with the Control group, which were downregulated after CGA supplementation. In conclusion, dietary supplementation CGA could protect against intestinal inflammation and injury by reducing the leakage of mtDNA and inactivating the cGAS-STING signaling pathway in broilers under NE challenge.

Von Willebrand factor promotes radiation-induced intestinal injury (RIII) development and its cleavage enzyme rhADAMTS13 protects against RIII by reducing inflammation and oxidative stress.

Patients with abdominopelvic cancer undergoing radiotherapy commonly develop radiation-induced intestinal injury (RIII); however, its underlying pathogenesis remains elusive. The von Willebrand factor (vWF)/a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) axis has been implicated in thrombosis, inflammation, and oxidative stress. However, its role in RIII remains unclear. In this study, the effect of radiation on vWF and ADAMTS13 expression was firstly evaluated in patients with cervical cancer undergoing radiotherapy and C57BL/6J mice exposed to different doses of total abdominal irradiation. Then, mice with the specific deletion of vWF in the platelets and endothelium were established to demonstrate the contribution of vWF to RIII. Additionally, the radioprotective effect of recombinant human (rh) ADAMTS13 against RIII was assessed. Results showed that both the patients with cervical cancer undergoing radiotherapy and RIII mouse model exhibited increased vWF levels and decreased ADAMTS13 levels. The knockout of platelet- and endothelium-derived vWF rectified the vWF/ADAMTS13 axis imbalance; improved intestinal structural damage; increased crypt epithelial cell proliferation; and reduced radiation-induced apoptosis, inflammation, and oxidative stress, thereby alleviating RIII. Administration of rhADAMTS13 could equally alleviate RIII. Our results demonstrated that abdominal irradiation affected the balance of the vWF/ADAMTS13 axis. vWF exerted a deleterious role and ADAMTS13 exhibited a protective role in RIII progression. rhADAMTS13 has the potential to be developed into a radioprotective agent.

Inflammation risk before cardiac surgery and the treatment effect of intraoperative dexamethasone.

Patients who exhibit high systemic inflammation after cardiac surgery may benefit most from pre-emptive anti-inflammatory treatments. In this secondary analysis (n = 813) of the randomised, double-blind Intraoperative High-Dose Dexamethasone for Cardiac Surgery trial, we set out to develop an inflammation risk prediction model and assess whether patients at higher risk benefit from a single intraoperative dose of dexamethasone (1 mg/kg). Inflammation risk before surgery was quantified from a linear regression model developed in the placebo arm, relating preoperatively available covariates to peak postoperative C-reactive protein. The primary endpoint was the interaction between inflammation risk and the peak postoperative C-reactive protein reduction associated with dexamethasone treatment. The impact of dexamethasone on the main clinical outcome (a composite of death, myocardial infarction, stroke, renal failure, or respiratory failure within 30 days) was also explored in relation to inflammation risk. Preoperatively available covariates explained a minority of peak postoperative C-reactive protein variation and were not suitable for clinical application (R2 = 0.058, P = 0.012); C-reactive protein before surgery (excluded above 10 mg/L) was the most predictive covariate (P < 0.001). The anti-inflammatory effect of dexamethasone increased as the inflammation risk increased (-0.689 mg/L per unit predicted peak C-reactive protein, P = 0.002 for interaction). No treatment-effect heterogeneity was detected for the main clinical outcome (P = 0.167 for interaction). Overall, risk predictions from a model of inflammation after cardiac surgery were associated with the degree of peak postoperative C-reactive protein reduction derived from dexamethasone treatment. Future work should explore the impact of this phenomenon on clinical outcomes in larger surgical populations.

HIF1α/miR-146α/TRAF6/NF-κB axis modulates hepatic iron overload-induced inflammation.

Transfusional therapy is used to cure anemia but raises the risk of hepatic iron overload (IO), which triggers oxidative stress damage, inflammation, and failure even fibrosis. microRNAs play a vital role in developing hepatic diseases. This study presented the mechanism by which IO induce hepatic inflammation through microRNAs. In this study, microRNA expression profiling in the liver was observed after IO for 2 weeks, in which the target microRNA will be found. IO activating the miR-146α/TRAF6/NF-κB pathway was validated, and the molecular mechanism of the IO-induced decrease of miR-146α in the liver was studied in vivo and in vitro. The expression of TRAF6/NF-κB (p65)-dependent inflammatory factors increased, whereas the expression of miR-146α decreased during the IO-induced inflammatory response in the liver. The reduced expression of HNF4α caused by HIF1α and miR-34α may decrease the expression of miR-146α. Overexpression of miR-146α alleviated the hepatic inflammatory response caused by IO. Our findings indicate that miR-146α is a key factor in inducing hepatic IO inflammation, which will be another potential target to prevent IO-induced hepatic damage.

Exclusive Enteral Nutrition Alleviates Th17-Mediated Inflammation via Eliminating Mechanical Stress-Induced Th17-Polarizing Cytokines in Crohn's-like Colitis.

BACKGROUND AND AIMS: Exclusive enteral nutrition (EEN) with a liquid diet is the only established dietary treatment for Crohn's' disease (CD). However, the mechanism of action of EEN in CD is unclear. T helper 17 (Th17) immune response plays a critical role in CD. We hypothesized that EEN alleviates Th17 response by eliminating mechanical stress-induced expression of Th17-polarizing cytokines. METHODS: A rat model of Crohn's-like colitis was established by intracolonic instillation of TNBS (65 mg/kg in 250 µL of 40% ethanol). Control rats were treated with saline. We characterized immunophenotypes and molecular changes of the colon in control and colitis rats with and without EEN treatment. Th17 differentiation was determined using coculture assays. RESULTS: TNBS instillation induced transmural inflammation with stenosis in the inflammation site and a marked increase of Th17-polarizing cytokines interleukin (IL)-6 and osteopontin and the Th17 cell population in the mechanically distended preinflammation site (P-site). EEN treatment eliminated mechanical distention and the increase of IL-6, osteopontin, and Th17 response in the P-site. IL-6 and osteopontin expression was found mainly in the muscularis externa. Mechanical stretch of colonic smooth muscle cells in vitro induced a robust increase of IL-6 and osteopontin. When naïve T cells were cultured with conditioned media from the P-site tissue or stretched cells, Th17 differentiation was significantly increased. Inhibition of IL-6, but not deletion of osteopontin, blocked the increase of Th17 differentiation. CONCLUSIONS: Mechanical stress induces Th17-polarizing cytokines in the colon. EEN attenuates Th17 immune response by eliminating mechanical stress-induced IL-6 in Crohn's-like colitis.