Diamine Oxidase Levels Research Articles

Predictive Value of the Serum Diamine Oxidase Level in the Diagnosis of Seasonal Allergic Rhinitis.

Allergic rhinitis (AR) is characterized by the increased sensitivity of the nasal mucosa to allergens and has a significant impact on life quality. There is promising evidence that biomarkers can help in the diagnosis, treatment, and follow-up of patients with AR. Diamine oxidase (DAO) is one of the enzymes responsible for the breakdown of histamine, the primary mediator of allergies. To investigate the significance of DAO as a useful biomarker for diagnosis and the severity of AR. In this case-control study, 24 patients and 24 healthy controls were recruited and their serum DAO levels, total IgE levels (using ELISA), blood eosinophil count, and percentage (using complete blood cell count) were measured. The sino-nasal outcomes test-22 (SNOT-22) questionnaire was used to assess the severity of symptoms in patients. The Receiver Operating Characteristic (ROC) analysis was used to assess the predictive power of DAO level for the diagnosis of AR. The relationship between DAO and disease severity, as well as other AR-related clinical factors, were also investigated. DAO levels were lower in AR patients compared with the controls. The DAO level did not significantly correlate with the severity of AR according to the Allergic Rhinitis and its Impact on Asthma (ARIA) score, though it was lower in patients with persistent or moderate to severe symptoms. The total IgE, eosinophil percentage, and SNOT-22 score all had an inverse relationship with DAO. Moreover, DAO was significantly associated with the diagnosis of AR, with an Area under the ROC Curve (AUC) of 0.771, a sensitivity of 75%, and a specificity of 62.5%. DAO might be a valuable biomarker in the diagnosis of allergic rhinitis.

Elevated serum levels of diamine oxidase, D-lactate and lipopolysaccharides are associated with metabolic-associated fatty liver disease.

Studies have suggested an association between metabolic-associated fatty liver disease (MAFLD) and intestinal barrier function. The present study aims to investigate the association between MAFLD and intestinal barrier impairment in humans and identify potential risk factors for MAFLD. A total of 491 patients were retrospectively enrolled in this study. The serum levels of diamine oxidase, D-lactate and lipopolysaccharide were measured to evaluate intestinal barrier integrity in patients with and without MAFLD. Binary logistic regression and correlational analyses were conducted to verify the association between MAFLD and serum levels of intestinal barrier biomarkers. We enrolled 294 patients with MAFLD and 197 patients without MAFLD in this study. Patients with MAFLD had higher serum levels of diamine oxidase, D-lactate and lipopolysaccharide (P < 0.001) than those without MAFLD. Multivariate logistic regression analyses showed that BMI [odds ratio (OR) 1.324; P < 0.001], triglycerides (OR 2.649; P = 0.002), nonesterified fatty acids (OR 1.002; P = 0.011), diamine oxidase (OR 1.149; P = 0.011) and D-lactate (OR 1.221; P < 0.001) were independent risk factors for MAFLD. Additionally, serum levels of diamine oxidase and D-lactate increase as liver steatosis became more severe. MAFLD patients with ≥2 metabolic abnormalities had higher serum levels of lipopolysaccharide (P = 0.034). MAFLD is associated with intestinal barrier impairment. Diamine oxidase and D-lactate are potential predictors of MAFLD, and their serum levels are related to liver steatosis. Intestinal barrier impairment is related to metabolic disorders in patients with MAFLD.

Transplanted hair follicle mesenchymal stem cells alleviated small intestinal ischemia–reperfusion injury via intrinsic and paracrine mechanisms in a rat model

Background: Small intestinal ischemia-reperfusion (IR) injury is a common intestinal disease with high morbidity and mortality. Mesenchymal stem cells (MSCs) have been increasingly used in various intestinal diseases. This study aimed to evaluate the therapeutic effect of hair follicle MSCs (HFMSCs) on small intestinal IR injury. Methods: We divided Sprague–Dawley rats into three groups: the sham group, IR group and IR + HFMSCs group. A small intestinal IR injury rat model was established by clamping of the superior mesenteric artery (SMA) for 30 min and reperfusion for 2 h. HFMSCs were cultured in vitro and injected into the rats through the tail vein. Seven days after treatment, the intrinsic homing and differentiation characteristics of the HFMSCs were observed by immunofluorescence and immunohistochemical staining, and the paracrine mechanism of HFMSCs was assessed by Western blotting and enzyme-linked immunosorbent assay (ELISA). Results: A small intestinal IR injury model was successfully established. HFMSCs could home to damaged sites, express proliferating cell nuclear antigen (PCNA) and intestinal stem cell (ISC) markers, and promote small intestinal ISC marker expression. The expression levels of angiopoietin-1 (ANG1), vascular endothelial growth factor (VEGF) and insulin growth factor-1 (IGF1) in the IR + HFMSCs group were higher than those in the IR group. HFMSCs could prevent IR-induced apoptosis by increasing B-cell lymphoma-2 (Bcl-2) expression and decreasing Bcl-2 homologous antagonist/killer (Bax) expression. Oxidative stress level detection showed that the malondialdehyde (MDA) content was decreased, while the superoxide dismutase (SOD) content was increased in the IR + HFMSCs group compared to the IR group. An elevated diamine oxidase (DAO) level reflected the potential protective effect of HFMSCs on the intestinal mucosal barrier. Conclusion: HFMSCs are beneficial to alleviate small intestinal IR injury through intrinsic homing to the small intestine and by differentiating into ISCs, via a paracrine mechanism to promote angiogenesis, reduce apoptosis, regulate the oxidative stress response, and protect intestinal mucosal function potentially. Therefore, this study suggests that HFMSCs serve as a new option for the treatment of small intestinal IR injury.

Electroacupuncture modulates gut microbiota in mice: A potential target in postoperative cognitive dysfunction.

The detailed mechanism of inflammation in postoperative cognitive dysfunction (POCD) is unclear. This study aimed to determine whether electroacupuncture (EA) ameliorates POCD by modulating gut microbial dysbiosis. Compared to the control group, mice in the EA group were treated at the acupoints Zusanli (ST36), Quchi (L111), Baihui (GV20), and Dazhui (GV14) 1 week before appendectomy. Novel object recognition and the Morris water maze tests were used to assess learning and spatial reference memory deficits, whereas hippocampus samples and stool samples were collected for central inflammatory tests and 16S-rRNA sequencing of intestinal flora, respectively. In amyloid precursor protein/presenilin 1 (APP/PS1) mice, EA enhanced spatial memory and learning deficits. The fecal microbial community was altered in APP/PS1 mice in the absence of EA following surgery. Among them, Coprococcus and Bacteroidetes were more abundant in the EA groups than in the control groups; however, Actinobacteriota, Helicobacteraceae, and Escherichia/shigella constitute the minor bacterial colonization in the EA groups. Furthermore, we found a significant negative correlation between Firmicutes and escape latency (Pearson correlation coefficient - 0.551, p < 0.01) and positive correlation between Proteobacteria and escape latency (Pearson correlation coefficient 0.462, p < 0.05). Electron microscopy revealed signs of blood-brain barrier (BBB) impairments and immunofluorescence images showed glial cells activated in the hippocampus of APP/PS mice without EA, and serum diamine oxidase levels were increased in these mice; whereas EA treatment significantly relieved the above pathological changes. Our findings implied that EA decreases hippocampal inflammation ofAPP/PS1 by upregulating benificial gut microbiota, reducing BBB and intestinal barrier dysfunction, thus alleviates postoperative cognitive dysfunction. This may provide a novel target in POCD management.

Dietary supplementation ellagic acid on the growth, intestinal immune response, microbiota, and inflammation in weaned piglets.

Piglets are susceptible to weaning stress, which weakens the barrier and immune function of the intestinal mucosa, causes inflammation, and ultimately affects animal growth and development. Ellagic acid (EA) is a natural polyphenol dilactone with various biological functions. However, The mechanisms underlying the effects of EA on animal health are still poorly known. Herein, we examined whether dietary supplementation with EA has a positive effect on growth performance, intestinal health, immune response, microbiota, or inflammation in weaned piglets. Sixty weaned piglets (age, 30 days) were randomly divided into two groups: the control group (basic diet) and the test group (basic diet + 500 g/t EA). The pigs were fed for 40 days under the same feeding and management conditions, and the growth performance of each individual was measured. At the end of the feeding period, samples were collected from the small intestinal mucosa for further analysis. Using these tissues, the transcriptome sequences and intestinal microbial diversity were analyzed in both groups. An inflammation model using small intestinal mucosal epithelial cells (IPEC-J2) was also constructed. Dietary EA supplementation significantly increased the average daily weight gain (ADG) and reduced diarrhea rate and serum diamine oxidase (DAO) levels of weaned piglets. Transcriptome sequencing results revealed 401 differentially expressed genes in the jejunum mucosal tissue of pigs in the control and test groups. Of these, 163 genes were up-regulated and 238 were down-regulated. The down-regulated genes were significantly enriched in 10 pathways (false discovery rate < 0.05), including seven pathways related to immune response. The results of bacterial 16s rDNA sequencing show that EA affects the composition of the intestinal microbiota in the cecum and rectum, and reveal significant differences in the abundances of Prevotella_9, Lactobacillus delbrueckii, and Lactobacillus reuteri between the test and control groups (P < 0.05). Experiments using the inflammation model showed that certain doses of EA promote the proliferation of IPEC-J2 cells, increase the relative mRNA expression levels of tight junction-related proteins (ZO-1 and Occludin), improve the compactness of the intestine, reduce the expression of inflammatory factors TNF-α and IL-6, and significantly reduce LPS-induced inflammation in IPEC-J2 cells. In conclusion, we found for the first time that dietary supplementation of EA affects the gut immune response and promotes the beneficial gut microbiota in weaned piglets, reduces the occurrence of inflammatory responses, and thereby promotes the growth and intestinal health of piglets.

Effect of Dexmedetomidine on Intestinal Barrier inPatients Undergoing Gastrointestinal Surgery-A Single-Center Randomized ClinicalTrial.

Gastrointestinal failure results in death in critically ill patients. This study aimed to explore the effect of dexmedetomidine (DEX) on intestinal barrier function and its mechanism in critically ill patients undergoing gastrointestinal surgery. Patients undergoing gastrointestinal surgery were randomized into the DEX group (n=21) or midazolam (MID) group (n=21). Sufentanil was used for analgesia in both groups. In the DEX group, DEX was loaded (1μg/kg) before sedation and infused (0.7μg/kg/h) during sedation. In the MID group, MID was loaded (0.05mg/kg) before sedation and infused (0.1mg/kg/h) during sedation. The mean arterial pressure , heart rate , borborygmus resumption time , first defecation time, length of intensive care unit stay, and length of hospital stay were observed. The diamine oxidase (DAO), D-lactate , TNF-α, IL-6, and α7nAChR levels in plasma or hemocytes were detected before the start of sedation (0h) and after sedation (24h). No significant differences in age, sex, body mass index, Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores were noted (P>0.05). The mean arterial pressure between 0h and 24h showed no significant difference between the groups (P>0.05), but the heart rate was significantly lower in the DEX group (P=0.042). The borborygmus resumption time was significantly earlier in the DEX group (P=0.034). The lengths of intensive care unit stay (P=0.016) and hospital stay (P=0.031) were significantly shorter in the DEX group. The TNF-α level in the DEX group was lower at 24h than 0h. The D-lactate level was significantly lower in the DEX group than the MID group at 24h(P=0.016). The expression of α7nAChR in the DEX group was significantly higher at 24h than 0h(P<0.05). DEX maintained intestinal barrier integrity in patients undergoing gastrointestinal surgery through the cholinergic anti-inflammatory pathway.

Integrated systematic pharmacology analysis and experimental validation to reveal the mechanism of action of Semen aesculi on inflammatory bowel diseases

Background and ethnopharmacological relevanceSemen aesculi (SA), a traditional Chinese herb, has been used in the treatment of gastrointestinal disease for thousands of years. The escin was the main components of SA. A growing number of research showed that escin has a wide range of pharmacological activities in intestinal barrier dysfunction. Aim of the studyInflammatory bowel diseases (IBD) are an idiopathic disease of the intestinal tract with the hallmark features of mucosal inflammation and loss of barrier function. The theory of traditional Chinese medicine (TCM) suggests that SA plays a potential role in protecting the gastrointestinal diseases. The present study aimed to explore the effects of SA on the intestinal barrier under existing inflammatory conditions and elucidate underlying mechanisms. Materials and methodsThe bioactive components of SA and their predicted biological targets were combined to develop a compound target pathway network. It is used to predict the bioactive components, molecular targets, and molecular pathways of SA in improving IBD. The ingredients of SA were extracted by decoction either in water and ethanol and separated into four fractions (AE, EE, PEE and PCE). The effects of extractions were evaluated in the lipopolysaccharide (LPS)-induced RAW264.7 macrophages cell model, LPS-induced intestinal barrier injury model and imodium-induced constipation model. The high-performance liquid chromatography (HPLC) analysis was performed to identify the bioactive components. ResultsThe compound-target pathway network was identified with 10 bioactive compounds, 166 IBD-related targets, and 52 IBD-related pathways. In LPS-induced RAW264.7 cells, PEE and PCE significantly decreased nitric oxide (NO) production and TNF-α level. In mice, PEE and PCE administration improved intestinal barrier damage, increased intestinal motility, reduced levels of TNF-α and diamine oxidase (DAO). Furthermore, PEE and PCE administration not only decreased expression of p-Akt, p-IκBα, nuclear p-p65, and TNF-α level, but also increased expression of the zonula occludin-1 (ZO-1) in LPS-induced intestinal barrier injury model. The escin content of AE, EE, PEE and PCE gradually increased with an increase of the bioactivity. ConclusionsEscin was the main bioactive components of SA. The effects of SA on IBD were mediated by repairing the intestinal barrier and promoting intestinal motility. The mechanism of action of SA is related to inhibiting the Akt/NF-κB signaling pathway in intestinal tissue, at least, in part. Our results provide a scientific basis for further exploring the mechanisms involved in the beneficial effects of SA in IBD.

Hexavalent Chromium Exposure Induces Intestinal Barrier Damage via Activation of the NF-κB Signaling Pathway and NLRP3 Inflammasome in Ducks.

Hexavalent chromium [Cr(VI)] is a dangerous heavy metal which can impair the gastrointestinal system in various species; however, the processes behind Cr(VI)-induced intestinal barrier damage are unknown. Forty-eight healthy 1-day-old ducks were stochastically assigned to four groups and fed a basal ration containing various Cr(VI) dosages for 49 days. Results of the study suggested that Cr(VI) exposure could significantly increase the content of Cr(VI) in the jejunum, increase the level of diamine oxidase (DAO) in serum, affect the production performance, cause histological abnormalities (shortening of the intestinal villi, deepening of the crypt depth, reduction and fragmentation of microvilli) and significantly reduced the mRNA levels of intestinal barrier-related genes (ZO-1, occludin, claudin-1, and MUC2) and protein levels of ZO-1, occludin, cand laudin-1, resulting in intestinal barrier damage. Furthermore, Cr(VI) intake could increase the contents of hydrogen peroxide (H2O2) and malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-18 (IL-18) but decrease the activities of total superoxide dismutase (T-SOD), catalase (CAT), and glutathione reductase (GR), as well as up-regulate the mRNA levels of TLR4, MyD88, NF-κB, TNFα, IL-6, NLRP3, caspase-1, ASC, IL-1β, and IL-18 and protein levels of TLR4, MyD88, NF-κB, NLRP3, caspase-1, ASC, IL-1β, and IL-18 in the jejunum. In conclusion, Cr(VI) could cause intestinal oxidative damage and inflammation in duck jejunum by activating the NF-κB signaling pathway and the NLRP3 inflammasome.

Gut Dysbiosis and Intestinal Barrier Dysfunction Promotes IgA Nephropathy by Increasing the Production of Gd-IgA1.

BackgroundImmunoglobulin A nephropathy (IgAN) is the most common type of primary glomerular disease in adults worldwide. Several studies have reported that galactose-deficient IgA1 (Gd-IgA1) is involved in the pathogenesis of IgAN.MethodsThirty-five patients with IgAN diagnosed with renal biopsy for the first time served as the experimental group, who were hospitalized in our department. Twenty normal healthy cases in the physical examination center of our hospital served as the control group. Then the levels of Gd-IgA1 in serum and urine, and intestinal mucosal barrier injury indexes [diamine oxidase (DAO), serum soluble intercellular adhesion molecule-1 (sICAM-1), D-lactate (D-LAC), and lipopolysaccharide (LPS)] and inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α)] in the serum samples were detected. Fecal samples were collected to detect intestinal microbiota using 16 s rDNA sequencing. Then, we assessed possible correlations among clinical and laboratory findings.ResultsIn patients with IgAN, the levels of Gd-IgA1 both in the serum and urine were higher than that of the healthy control. Furthermore, urine Gd-IgA1 level was positively correlated with the serum creatinine level, 24 h urine protein, and M, S, and T parameters in the Oxford classification. ROC curve analysis showed that urine Gd-IgA1 has a greater diagnostic value (AUC = 0.9714, 95% CI, 0.932–1; P < 0.0001) for IgAN. The best cutoff value for urine Gd-IgA1 was 0.745 ng·l/ml·μmol (sensitivity, 94%; specificity, 95%). The intestinal mucosal barrier damage indexes (DAO, sICAM-1, D-LAC, and LPS) were increased in the patients with IgAN, which were positively correlated with Gd-IgA1 levels (P < 0.05) both in serum and urine. The levels of inflammatory factors in the patients with IgAN were increased. 16 s rDNA analysis showed that the intestinal microbiota in these patients was disordered compared to that observed in the healthy subjects. Actinobacteria, Bifidobacterium, Blautia, Bifidobacteriaceae, and Bifidobacteriales were decreased and Shigella was increased in IgAN. The decreased populations of these flora were negatively and significantly correlated with urine Gd-IgA1 and the levels of DAO, sICAM-1, D-LAC, and LPS.ConclusionThe urine Gd-IgA1 levels may be a non-invasive biological marker for evaluating kidney injury in IgAN. Gut flora dysbiosis and intestinal barrier dysfunction may be involved in Gd-IgA1 expression.

Effect of dietary Pinus densiflora bark extract on nutrient utilization and intestinal health in weaned piglets

Pinus densiflora bark extracts (PBE) has been widely used in health care medicine and animal husbandry by its beneficial physiological functions such as antioxidant activity, anti-inflammatory, antibacterial and antiviral activity. The study aimed to investigate the effect of dietary level of PBE on diarrhea rate, nutrient digestibility and intestinal health in weaned piglets. 120 crossbreed pigs were divided randomly into 4 treatment groups (0, 100, 200, 300 mg/kg PBE, respectively), with 3 replicates per treatment and 10 piglets per replicate. The experiment lasted for 28 d. Dietary supplementation with PBE significantly decreased diarrhea rate and diarrhea index (p < 0.0001). The groups supplemented with dietary PBE showed significant decrease in total tract apparent digestibility (TTAD) of crude protein (CP), gross energy (GE) and ether extracts (EE) (p < 0.05), while there was no significant effect of TTAD on dry matter (DM). Interestingly, the trypsin was not affected by dietary PBE, and the lipase and amylase activities decreased significantly in pigs fed diets supplemented with PBE (p < 0.05). The levels of total protein and glucose in serum were significantly increased by adding PBE in diets (p < 0.05), and levels of diamine oxidase (DAO) and endotoxin in serum were reduced by PBE supplementation (p < 0.05). The mRNA expression levels of tight junction proteins in the jejunum were significantly up-regulated compared to control. This study revealed that PBE supplementation decreased nutrient utilization and decreased diarrhea rate with improvement of the intestinal health in weaned piglets, and suggested appropriate dietary concentration of PBE supplementation would be 200 mg/kg.

Fermented soybean meal increases nutrient digestibility via the improvement of intestinal function, anti-oxidative capacity and immune function of weaned pigs

The nutritional components of fermented soybean meal (FSBM) vary because of the complex process of microbial fermentation. The objective of this study was to investigate the nutritional value of FSBM from two sources and explore the mode of actions of FSBM on the improvement of nutrient digestibility with the measurements of digestive enzymes and serum biomarkers. Eight weaned barrows (initial BW: 14.12 ± 0.24 kg) equipped with T-cannula in the distal ileum were allotted to a duplicated 4 × 4 Latin-square design with four experimental diets and four periods. Four experimental diets included a soybean meal control diet, two FSBM diets, and a nitrogen-free diet. The two sources of FSBM increased the contents of CP, amino acid and lactic acid, while decreased the levels of anti-nutritional factors, including glycinin, β-conglycinin and trypsin inhibitors. Compared to soybean meal control diet, both FSBM diets significantly increased the apparent and standardised ileal digestibility of CP and amino acids (P < 0.05), increased the activities of lipase, maltase and invertase in digesta (P < 0.05), increased total antioxidant capacity, activities of glutathione peroxidase and superoxide dismutase, the levels of interleukin-4, IgA, IgG and IgM in serum (P < 0.05), while decreased the levels of diamine oxidase, malondialdehyde, interleukin-6, and interleukin-2 in serum (P < 0.05). Additionally, the standardised ileal digestibility of amino acids were highly correlated with the aforementioned digestive enzymes and health-related serum biomarkers. In summary, FSBM diets showed an improved nutritional value evidenced by the higher nutrient digestibility, which may be partially derived from its beneficial effects on intestinal integrity, anti-oxidative capacity and immune function.

Correlation between Intestinal Microflora in Irritable Bowel Syndrome and Severity.

Background Irritable bowel syndrome (IBS) is a common chronic functional gastrointestinal disease accompanied by changes in intestinal microecology. This study investigated the relationship between gut microbiota and disease severity in patients with irritable bowel syndrome (IBS). Methods An observational study was performed on 60 IBS patients (study group) and 20 healthy controls admitted to our hospital from January 2013 to December 2014. Fecal samples were taken after admission to measure intestinal flora including Bifidobacterium, Lactobacillus, Enterobacter, and Enterococcus, and patient blood was collected to determine serum D-lactate and diamine oxidase (DAO) levels. The gut microbiota and serum markers of the two groups were analyzed. The correlation of gut microbiota index levels and serum markers with disease severity, as well as the correlation between gut microbiota index levels and serum markers, were analyzed. Results The levels of intestinal Lactobacillus and Bifidobacterium were lower, while the levels of Enterococcus and Enterobacter and serum D-lactate were higher in the study group than those in the control group. The levels of intestinal Lactobacillus and Bifidobacterium were lower, while the levels of Enterococcus and Enterobacter, serum D-lactate, and DAO were higher in patients with moderate IBS than those in patients with mild IBS. The levels of intestinal Lactobacillus and Bifidobacterium were lower in patients with severe IBS than those with moderate IBS, while the levels of Enterococcus and Enterobacter, serum D-lactate, and DAO were higher in patients with severe IBS. There was a significant negative correlation between the levels of Lactobacillus and Bifidobacterium and disease severity and a significant positive correlation between the levels of Enterococcus and Enterobacter, D-lactate, and DAO and disease severity. There was a significant negative correlation between the levels of Lactobacillus and Bifidobacterium and serum D-lactate and DAO, while there was a significant positive correlation between the levels of Enterococcus and Enterobacter and serum D-lactate and DAO (P < 0.05). Conclusion Intestinal flora, D-lactate, and DAO were abnormal in IBS patients, and intestinal flora was closely correlated with disease severity, D-lactate, and DAO levels.

Exploring Standardized Scales and Serum Biomarkers to Evaluate Changes in Pruritus due to Eczema after Japanese Kampo Treatment: A Prospective Case Series

Background: We aimed to explore standardized scales and serum biomarkers for tracking changes in the symptoms and severity of pruritus due to eczema in patients treated with Kampo formulas. Patients and Methods: This prospective, single-arm, pre-post comparison case series recruited patients with pruritus mostly due to eczema who consulted the Kampo Clinic at the Keio University Hospital from June 2019 to March 2020. The participants were prescribed a personalized Kampo formula for 12 weeks. Patient profiles and symptoms were assessed every 4 weeks using the visual analog scale (VAS), patient-oriented eczema measure (POEM) scale, 5-D itch scale (5D), Skindex-16, and eczema area and severity index (EASI). Blood biomarkers and intestinal permeability indicators were measured at the first consultation and 12 weeks later. Results: Pruritus and eczema severity improved significantly over time. The VAS, POEM, 5D, and Skindex-16 scores were well-correlated. The serum interleukin-31 levels decreased significantly after a 12-week intervention. Changes in the interleukin-31 level correlated with the diamine oxidase level at week 0, suggesting the involvement of the Th2 immune system and intestinal permeability in the mechanism of Kampo formulas. Conclusion: The evaluated scales are suitable for evaluating subjective symptoms and eczema severity after Kampo treatment; further studies are required to verify the study findings.

Electroacupuncture in Treatment of Acute Gastrointestinal Injury in Patients with Severe Traumatic Brain Injury: A Multicenter Randomized Controlled Trial.

To evaluate whether electroacupuncture (EA) would improve gastrointestinal function and clinical prognosis in patients with severe traumatic brain injury (TBI) complicocted by acute gastrointestinal injury (AGI). This multicenter, single-blind trial included patients with TBI and AGI admitted to 5 Chinese hospitals from September 2018 to December 2019. A total of 500 patients were randomized to the control or acupuncture groups using a random number table, 250 cases in each group. Patients in the control group received conventional treatment, including mannitol, nutritional support, epilepsy and infection prevention, and maintenance of water, electrolytes, and acid-base balance. While patients in the acupuncture group received EA intervention at bilateral Zusanli (ST 36), Shangjuxu (ST 37), Xiajuxu (ST 39), Tianshu (ST 25), and Zhongwan (RN 12) acupoints in addition to the conventional treatment, 30 min per time, twice daily, for 7 d. The primary endpoint was 28-d mortality. The secondary endpoints were serum levels of D-lactic acid (D-lac), diamine oxidase (DAO), lipopolysaccharide (LPS), motilin (MTL) and gastrin (GAS), intra-abdominal pressure (IAP), bowel sounds, abdominal circumference, AGI grade, scores of gastrointestinal failure (GIF), Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation (APACHE II), Sequential Organ Failure Assessment (SOFA), and Multiple Organ Dysfunction Syndrome (MODS), mechanical ventilation time, intense care unit (ICU) stay, and the incidence of hospital-acquired pneumonia. The 28-d mortality in the acupuncture group was lower than that in the control group (22.80% vs. 33.20%, P<0.05). Compared with the control group, the acupuncture group at 7 d showed lower GIF, APACHE II, SOFA, MODS scores, D-lac, DAO, LPS, IAP, and abdominal circumference and higher GCS score, MTL, GAS, and bowel sound frequency (all P<0.05). In addition, the above indices showed simillar changes at 7 d compared with days 1 and 3 (all P<0.05) in the EA group. Early EA can improve gastrointestinal function and clinical prognosis in patients with severe TBI complicated by AGI. (Registration No. ChiCTR2000032276).

Ellagic Acid Improves Antioxidant Capacity and Intestinal Barrier Function of Heat-Stressed Broilers via Regulating Gut Microbiota.

Simple SummaryEnvironmental heat stress easily damages feed intake, intestinal health, and growth performance of broilers. Ellagic acid (EA), a natural polyphenol antioxidant in fruits or nuts, is beneficial to animal health. For the first time, we revealed that dietary EA improved antioxidant capacity and the intestinal barrier function of heat-stressed broilers probably via regulating gut microbiota. Therefore, it is proposed that EA could be exploited as a feed additive to alleviate heat stress-induced oxidative damages in broilers.Heat stress (HS) has been revealed to damage the antioxidant system and intestinal barrier function, which greatly threatens poultry production. The present study investigated the effects of dietary ellagic acid (EA) on the antioxidant system, gut barrier function, and gut microbiota of heat-stressed broilers. Arbor Acres 14-day-old broilers numbering 360 were randomly divided into six groups, including one negative control group (NC) and five experimental groups. The broilers in the NC group were supplemented with a basal diet at a normal temperature (23 ± 2 °C). The broilers in the experimental groups were supplemented with basal diets containing EA at different doses (0, 75, 150, 300, and 600 mg/kg) at HS temperature (35 ± 2 °C). The experiment lasted for 4 weeks. Results showed that dietary EA reduced the corticosterone (CORT), LPS, and diamine oxidase (DAO) levels in the serum of heat-stressed broilers. Additionally, dietary EA improved the antioxidant enzyme activity and mRNA levels of Nrf2/HO-1 in the ileum of heat-stressed broilers. The relative abundances of Streptococcus, Ruminococcus_torques, Rothia, Neisseria, Actinomyces, and Lautropia in the cecum were significantly reduced by the EA supplementation in a dose-dependent manner. Notably, the LPS, DAO, and MDA in the serum were revealed to be positively correlated with the relative abundances of Rothia, Neisseria, Actinomyces, and Lautropia, while the GSH-px, SOD, and CAT levels in the serum were negatively correlated with the relative abundances of Ruminococcus_torques, Rothia, Neisseria, Actinomyces, Streptococcus, and Lautropia. Taken together, dietary EA improved the antioxidant capacity, intestinal barrier function, and alleviated heat-stressed injuries probably via regulating gut microbiota.

An Antioxidant Supplement Function Exploration: Rescue of Intestinal Structure Injury by Mannan Oligosaccharides after Aeromonas hydrophila Infection in Grass Carp (Ctenopharyngodon idella).

Mannan oligosaccharides (MOS) are a type of functional oligosaccharide which have received increased attention because of their beneficial effects on fish intestinal health. However, intestinal structural integrity is a necessary prerequisite for intestinal health. This study focused on exploring the protective effects of dietary MOS supplementation on the grass carp’s (Ctenopharyngodon idella) intestinal structural integrity (including tight junction (TJ) and adherent junction (AJ)) and its related signalling molecule mechanism. A total of 540 grass carp (215.85 ± 0.30 g) were fed six diets containing graded levels of dietary MOS supplementation (0, 200, 400, 600, 800 and 1000 mg/kg) for 60 days. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila for 14 days. We used ELISA, spectrophotometry, transmission electron microscope, immunohistochemistry, qRT-PCR and Western blotting to determine the effect of dietary MOS supplementation on intestinal structural integrity and antioxidant capacity. The results revealed that dietary MOS supplementation protected the microvillus of the intestine; reduced serum diamine oxidase and d-lactate levels (p < 0.05); enhanced intestinal total antioxidant capacity (p < 0.01); up-regulated most intestinal TJ and AJ mRNA levels; and decreased GTP-RhoA protein levels (p < 0.01). In addition, we also found several interesting results suggesting that MOS supplementation has no effects on ZO-2 and Claudin-15b. Overall, these findings suggested that dietary MOS supplementation could protect intestinal ultrastructure, reduce intestinal mucosal permeability and maintain intestinal structural integrity via inhibiting MLCK and RhoA/ROCK signalling pathways.

Protective effect and possible mechanism of arctiin on broilers challenged by Salmonella pullorum.

This study was aimed to investigate the effects of dietary arctiin (ARC) supplementation (100, 200, and 400 mg/kg) on the growth performance and immune response of broilers after a Salmonella pullorum (S. pullorum) challenge, and we conducted in vitro antibacterial test to explore the bacteriostatic mechanism of ARC. The in vivo trial was randomly assigned to six groups: noninfected control (NC) group and positive control (PC) group received a basal diet; TET group, received a basal diet supplemented with 100 mg/kg chlortetracycline; ARC100, ARC200, and ARC400 groups received a basal diet containing 100, 200, and 400 mg/kg ARC, respectively. From days 14 to 16, all birds (except the NC group) were infected with 1 mL (1 × 108 CFU per mL) fresh S. pullorum culture by oral gavage per day. In vivo results showed that dietary supplementation of 200 mg/kg ARC significantly increased average daily gain (P < 0.05) and decreased feed-to-gain ratio of broilers vs. the PC group during days 15 to 28 after being challenged with S. pullorum (P < 0.05). The jejunal crypt depth (CD) was decreased by supplementing 100 or 200 mg/kg ARC in diets compared with PC birds at day 19 (P < 0.05). The jejunal villi height (VH) was increased by supplementing 100, 200, or 400 mg/kg ARC in diets compared with PC birds at day 28 (P < 0.05). Besides, dietary supplementation of 200 mg/kg ARC increased the jejunal VH to CD ratio than the PC group both at days 19 and 28 (P < 0.05). Notably, the broilers had lower serum lipopolysaccharide and diamine oxidase levels in the ARC100 and ARC200 groups at day 28 than those in the PC group (P < 0.05). Furthermore, in comparison to PC birds, the birds in ARC groups (100, 200, and 400 mg/kg) had higher serum contents of IgM and IL-10, and the birds in the ARC200 group had higher serum contents of IgA at day 19 (P < 0.05). At day 28, the birds in ARC groups (100, 200, and 400 mg/kg) had lower serum contents of IL-8, and the birds in the ARC200 group had lower serum contents of IFN-γ compared with PC birds (P < 0.05). The in vitro experiment showed that ARC significantly inhibited the biofilm formation and adhesion of S. pullorum (P < 0.05). Metabonomics analysis revealed that ARC can restrain the formation of the biofilm by affecting a variety of metabolic pathways of S. pullorum. Therefore, dietary supplementation of 200 mg/kg ARC might be a potential way to substitute antibiotics to control S. pullorum infection in broilers.

Effects of Chlorogenic Acid on Performance, Anticoccidial Indicators, Immunity, Antioxidant Status, and Intestinal Barrier Function in Coccidia-Infected Broilers.

Simple SummaryCoccidiosis impairs the growth performance, intestinal health, and immunity of broilers, resulting in significant economic losses to the poultry industry. The use of anticoccidial drugs can lead to the emergence of resistant strains and drug resistance, and the control effect of vaccines is limited. Thus, there is an urgent need to develop substitutes for anticoccidial drugs. Chlorogenic acid (CGA) was reported to have positive effects on the performance and intestinal health of broilers. However, little is known about the application and mechanism of CGA in coccidia-infected broilers. The results of this study showed that dietary supplementation with CGA exhibited anticoccidial activities, and improved growth performance, immunity, antioxidant status, and intestinal barrier function in coccidia-infected broilers.The effects of chlorogenic acid (CGA) on growth performance, anticoccidial indicators (oocysts per gram of excreta, cecal lesion score, and bloody diarrhea score), immunity, antioxidant status, and intestinal barrier function in coccidia-infected broilers were investigated. A total of 240 one-day-old Arbor Acres broilers were randomly divided into four groups with six replicates of ten broilers each for 42 days. Four treatments included control diet (non-infected control, NC), control diet +Eimeria infection (infected control, IC), control diet +0.5 g/kg CGA + Eimeria infection (CGA0.5), and control diet +1 g/kg CGA + Eimeria infection (CGA1). At day 14, each broiler in IC, CGA0.5, and CGA1 groups was orally inoculated with 1 mL saline containing 4 × 105 sporulated oocysts. The results showed that the CGA1 group increased the average daily gain by 12.57% (p < 0.001) and decreased the feed/gain ratio (p = 0.010) and mortality (p = 0.030) by 13.00% and 77.76%, respectively, of broilers from 14 to 42 days compared with the IC group. The CGA1 group decreased the oocysts per gram of excreta (p < 0.001) and bloody diarrhea score (p = 0.001) compared with the IC group. The CGA0.5 and CGA1 groups increased total antioxidant capacity (p < 0.001) at day 21 and villus height (p < 0.001) in the duodenum and jejunum at day 42, and decreased the levels of interleukin 6 (IL-6) (p = 0.002), malondialdehyde (MDA) (p < 0.001), D-lactic acid (p < 0.001), and diamine oxidase (DAO) (p < 0.001) at day 21 and the levels of MDA (p < 0.001) and D-lactic acid (p = 0.003) at day 42 compared with the IC group. In the CGA1 group, villus height in the duodenum (p < 0.001) and jejunum (p = 0.017) increased at day 21 and in the ileum (p < 0.001) at day 42, and the level of DAO (p < 0.001) decreased at day 42 compared with the IC group. Broilers in the IC group had a higher IL-6 level (p = 0.048) at day 42 and lower IL-10 (p = 0.027) and immunoglobulin A (p = 0.042) levels at day 21, and IL-10 level (p = 0.017) at day 42 than those in the NC group, while no significant differences were observed among the NC, CGA0.5, and CGA1 groups. In conclusion, dietary supplementation with 1 g/kg CGA improved growth performance, immunity, antioxidant status, and intestinal barrier function in coccidia-infected broilers.

Basal Serum Diamine Oxidase Levels as a Biomarker of Histamine Intolerance: A Retrospective Cohort Study.

Background: Histamine Intolerance (HIT) is a multifaceted pseudoallergic disorder possibly due to defective histamine metabolism. Diamine oxidase (DAO) contributes to histamine degradation and can be measured in the serum. The role of DAO measurement in the diagnostic work-up of HIT still remains unclear, and conflicting results have been reported in the literature. Therefore, we aimed to evaluate the possible clinical usefulness and consistency of DAO value ranges as provided by the assay manufacturer and verify whether they could predict the response to treatment. Methods: We retrospectively analyzed 192 outpatients with HIT symptoms and measured serum DAO values at baseline. Patients were prescribed either with low-histamine diet and/or enzymatic supplementation according to symptom severity and re-evaluated six to eight months later. Patients were stratified into three groups according to DAO levels: <3 U/mL, 3–10 U/mL, and >10 U/mL. HIT severity was assessed on a scale of 1 to 5 before and after treatment. Results: A total of 146 patients completed the study. Gastrointestinal and cutaneous symptoms, often associated with headache, were more frequent in subjects with DAO < 10 U/mL. Symptom severity and DAO ranges were correlated. Patients with intermediate DAO levels (3–10 U/mL) showed a more complex clinical phenotype but also a more significant improvement in symptom severity (score reduction 50%, interquartile range (IQR) = 33–60%) when compared to patients with low DAO (40%, IQR = 20–60%; p = 0.045) or high DAO (33%, IQR = 0–50%; p < 0.001). Complex clinical phenotypes were also more frequent in patients with intermediate DAO levels. Conclusions: HIT is characterized by typical symptoms and low levels of DAO activity. Symptom severity was associated with the degree of DAO deficiency. Patients with DAO values between 3 and 10 U/mL show the best response to treatment (low-histamine diet and/or DAO supplementation). DAO value could arguably be considered as a predictor of clinical response to treatment. Prospective studies are needed to confirm these data.

Effect of TRAF6 in acute pancreatitis-induced intestinal barrier injury via TLR4/NF-κB signal pathway

BackgroundThe aim of this study was to investigate the effect of tumor necrosis factor receptor-related factor 6 (TRAF6) in acute pancreatitis (AP)-induced intestinal barrier injury via the Toll-like receptor 4/nuclear factor kappa-B (TLR4/NF-κB) signal pathway. MethodsRat models of acute edematous pancreatitis (AEP) and acute necrotizing pancreatitis (ANP) were established by intraperitoneal injection of caerulein and retrograde infusion of sodium taurocholate solution into the biliopancreatic duct, respectively. Separate groups of model rats were pretreated with the TRAF6 inhibitor, MG-132. Rats were sacrificed at 12 h after the last injection for inducing AP. Histopathological changes, inflammatory response, intestinal barrier function, and protein expression levels were assessed by pathological score, ELISA, TUNEL, qRT-PCR, immunohistochemistry and western blotting. ResultsRat models of AEP and ANP were successfully established as evidenced by the pathological changes in the pancreas and intestine. Pre-treatment with MG-132 significantly alleviated pancreatic and intestinal pathological scores, reduced serum levels of amylase, IL-1β, and IL-6, and ameliorated apoptosis of mucosal cells. MG-132 reduced intestinal barrier injury, including serum levels of diamine oxidase and lipopolysaccharide, and intestinal expressions of ZO-1 and occludin. Moreover, it significantly suppressed the activation of the intestinal TLR4/NF-κB signaling pathway. ConclusionsTRAF6 inhibitor alleviated pancreatic and intestinal injury in AEP and ANP. This effect may be mediated through inhibition of the TLR4/NF-κB signaling pathway, which in turn regulates the inflammatory response and intestinal barrier injury.