Soybean glycinin impaired immune function and caused inflammation associated with PKC-ζ/NF-κb and mTORC1 signaling in the intestine of juvenile grass carp (Ctenopharyngodon idella).

Glycinin is a major protein and antinutritional factor of soybean. However, how dietary glycinin affect intestinal immune function of fish were largely unknown. In this study, we used juvenile grass carp as a model to investigate the impacts of glycinin on intestinal immune function of fish and involved mechanisms. We set three treatments including control, glycinin and glycinin + glutamine in this trial. For immune components, results revealed that compared with control group, glycinin group had lower acid phosphatase activities in the foregut, midgut and hindgut, lower C3 and C4 content, and lower mRNA abundances of IgM, IgZ, hepcidin, LEAP-2A, LEAP-2B and ß-defensin-1 in the midgut and hindgut rather than foregut of grass carp. For pro-inflammatory cytokines and relevant signaling, glycinin elevated mRNA abundances of IL-1ß, IL-8, IL-12p35, IL-12p40 and IL-17D in the midgut and IL-1ß, IFN-γ2, IL-6, IL-8, IL-12p35, IL-12p40 and IL-17D in the hindgut, and increased protein abundances of PKC-ζ and nuclear NF-κB p65 in the midgut and hindgut in comparison to control. For anti-inflammatory cytokines and relevant signaling, glycinin reduced mRNA abundances of TGF-ß1, TGF-ß2, IL-4/13B (rather than IL-4/13A), IL-10 and IL-11 in the midgut and hindgut, and reduced p-mTOR (Ser 2448), p-S6K1 (Thr 389) and p-4EBP1 (Thr 37/46) protein abundances in the midgut and hindgut rather than foregut. Co-administration of glutamine with glycinin could partially enhance intestinal function and reduce intestinal inflammation compared with glycinin treatment. Concluded, glycinin decreased intestinal immune components and caused intestinal inflammation associated with PKC-ζ/NF-κB and mTORC1 signaling.

The dynamic process of dietary soybean ß-conglycinin in digestion, absorption, and metabolism among different intestinal segments in grass carp (Ctenopharyngodon idella).

The present study aimed to investigate the dynamic process of soybean ß-conglycinin in digestion, absorption, and metabolism in the intestine of grass carp (Ctenopharyngodon idella). Fish fed with 80 g ß-conglycinin/kg diet for 7 weeks, the intestinal digestive enzyme was extracted to hydrolyze ß-conglycinin in vitro, the free amino acid and its metabolism product contents in intestinal segments were analyzed. The present study first found that ß-conglycinin cannot be thoroughly digested by fish intestine digestive enzyme and produces new products (about 60- and 55-kDa polypeptides). The indigestible ß-conglycinin further caused the free amino acid imbalance, especially caused free essential amino acid deficiency in the proximal intestine but excess in the distal intestine. Moreover, these results might be partly associated with the effect of ß-conglycinin in amino acid transporters and tight junction-regulated paracellular pathway. Finally, dietary ß-conglycinin increased the content of amino acid catabolism by-product ammonia while decreased the amino acid anabolism product carnosine content in the proximal intestine and distal intestine. Thus, the current study first and systemically explored the dynamic process of ß-conglycinin in digestion, absorption, and metabolism, which further supported our previous study that dietary ß-conglycinin suppressed fish growth and caused intestine injure.

Soybean ß-conglycinin caused intestinal inflammation and oxidative damage in association with NF-κB, TOR and Nrf2 in juvenile grass carp (Ctenopharyngodon idella): varying among different intestinal segments.

The current study aimed to investigate the effects and mechanisms of dietary soybean ß-conglycinin in immune function and oxidative damage among different intestinal segments of juvenile grass carp (Ctenopharyngodon idella). 240 fish (13.77 ±â€¯0.10 g) were fed control or 8% ß-conglycinin diet for 7 weeks. Dietary ß-conglycinin caused inconsistent suppression effects on the innate immune by decreasing complement component, lysozyme, antimicrobial peptide and acid phosphatase among different intestinal segments. Meanwhile, dietary ß-conglycinin caused inflammation in the mid and distal intestine by raising pro-inflammatory cytokines and declining anti-inflammatory cytokines mRNA levels, while more serious in the distal intestine than in the mid intestine. Furthermore, dietary ß-conglycinin regulating inflammatory cytokines might be associated with transcription factors nuclear factor-κB P65 (NF-κB P65) nucleus translocation and target of rapamycin (TOR) phosphorylation in the distal intestine but only related to TOR phosphorylation in the mid intestine. Interestingly, in the proximal intestine, dietary ß-conglycinin decreased both pro-inflammatory and anti-inflammatory cytokines mRNA level, and did not affect NF-κB P65 nucleus translocation and TOR phosphorylation. For oxidative damage, dietary ß-conglycinin exposure elevated both malondialdehyde (MDA) and protein carbonyl (PC) contents in the distal intestine, which might be attributed to the suppression of the Mn-SOD, catalase (CAT) and glutathione peroxidase (GPx) activities. In the mid intestine, dietary ß-conglycinin only increased PC content in association with the low activities of CAT, GPx and glutathione peroxidase (GR). Unexpectedly, in the proximal intestine, dietary ß-conglycinin did not significantly change MDA and PC contents while decreased antioxidant enzyme activities. Furtherly, dietary ß-conglycinin affect the antioxidant enzyme activity might be regulated by the varying pattern of nuclear factor-erythroid 2-related factor 2 (Nrf2) nucleus translocation among these three intestinal segments. In summary, dietary ß-conglycinin caused intestinal inflammation and oxidative damage in association with NF-κB, TOR and Nrf2 signaling molecules, which were varying among the three intestinal segments of grass carp.

Outcomes of microsurgical clipping vs coil embolization for ruptured aneurysmal subarachnoid hemorrhage: A multicenter real-world analysis of 583 patients in China.

Aneurysmal subarachnoid hemorrhage (SAH) is a complex neurovascular syndrome with high disability and mortality. SAH patients may be managed with surgical clipping or coil embolization. In this study, we provided a real-world analysis of the outcome and prognostic factors of aneurysmal SAH in patients treated with coil embolization or microsurgical clipping.We retrospectively analyzed the medical records of aneurysmal SAH patients (n = 583) who underwent treatment at the First Hospital and the Second Hospital of Hebei Medical University, and Tangshan Worker's Hospital in China. All patients were evaluated by a combined neurosurgery and interventional neuroradiology team. Microsurgical aneurysmal clipping was performed using the skull base approach, while coil embolization was performed with bare platinum coils (with or without balloon assistance). The primary outcome was the Glasgow Outcome Scale (GOS) score at discharge.A total of 583 patients were included in this study, of which 397 (68.1%) of them underwent clipping and 186 (31.9%) received coil embolization. The patient cohort consisted of both poor grade and good grade aneurysmal SAH: 441 (75.6%) patients had good-grade (Hunt and Hess grade II or III) and 142 (24.4%) had poor grade (Hunt and Hess grade IV or V). Overall, 123 (21%) patients had unfavorable neurologic outcome (GOS score 1-3) and 460 (78.9%) patients had favorable neurologic outcome (GOS score 4 or 5). The mean GOS score at discharge was comparable for patients who underwent clipping and those received coil embolization (P > .05). Multivariate analysis showed that clipping only [OR (95%CI): 0.03 (0.01, 0.36); P = .000] and clipping with CSF drainage [OR (95%CI): 0.41 (0.18, 0.89); P = .001] were independent factors of a favorable outcome in patients with aneurysmal SAH. Coil embolization with hematoma removal [OR (95%CI): 0.03 (0.01, 0.36); P = .000] was also an independent determinant of a favorable outcome. High baseline Fisher grades were associated with significantly increased risk of an unfavorable outcome [OR (95%CI): 2.08 (1.30, 3.33); P = .002].Our findings suggested that both coil embolization and microsurgical clipping are viable treatment options for aneurysmal SAH patients. Procedures, such as CSF drainage and hematoma removal, performed in parallel with coil embolization and chipping should be considered when treating individual patients.

Soybean glycinin decreased growth performance, impaired intestinal health, and amino acid absorption capacity of juvenile grass carp (Ctenopharyngodon idella).

The present study evaluated the influence of dietary soybean glycinin on growth performance, intestinal morphology, free intestinal amino acid (AA) content, and intestinal AA transporter (AAT) mRNA levels in juvenile grass carp (Ctenopharyngodon idella). Results were displayed as follows: (1) 8% dietary glycinin decreased growth performance, inhibited intestinal growth, and caused intestinal histology damage of grass carp; (2) dietary glycinin decreased the content of free neutral AAs including Val, Ser, Tyr, Ala, Pro, and Gln in all intestinal segments, and Thr, Ile, Leu, Phe, and Gly in the MI and DI while downregulated the mRNA levels of corresponding transporters including SLC38A2, SLC6A19b, and SLC6A14 in all intestinal segments, and SLC7A5, SLC7A8, and SLC1A5 in the MI and DI. Dietary glycinin decreased the content of free basic AAs including Arg in the MI and DI and His in all intestinal segments while downregulated cationic AAT SLC7A1 mRNA levels in the MI and DI. Dietary glycinin decreased the content of free acidic AAs including Glu in all intestinal segments and Asp in the MI and DI while decreased mRNA levels of corresponding transporters including SLC1A2a in all intestinal segments and SLC1A3 in the MI and DI; (3) the digestion trial showed that basic subunits of glycinin was hard to digest in the intestine of grass carp; (4) co-administration of glutamine with glycinin partially alleviated the negative effects. Overall, glycinin decreased intestinal AA absorption capacity partly contributed by decreased AATs' mRNA levels and the indigestibility of glycinin.

[Interpretation of the disaster response plans in the pediatric intensive care unit].

In April 2018, the Group of Pediatric Disasters, Pediatric Society, Chinese Medical Association and Pediatric Committee, Medical Association of Chinese People's Liberation Army issued the disaster response plans in the pediatric intensive care unit (PICU). This article outlines the development of the plans and the implementation of PICU disaster rescue, along with ethical issues in the context of disasters and psychological reconstruction after a disaster.

Apolipoprotein E gene polymorphism and the risk of subarachnoid hemorrhage: a meta-analysis of case-control studies.

BACKGROUND: Studies investigating the association between the apolipoprotein E gene (APOE) polymorphism and the risk of subarachnoid hemorrhage (SAH) have reported inconsistent results. So we performed a meta-analysis to estimate the association between APOE polymorphism and SAH susceptibility. METHODS: Relevant studies published before 5 November 2015 were identified by searching PubMed, Embase, EBSCO, and ISI web of knowledge. The strength of relationship between the APOE gene and SAH susceptibility was assessed using odds ratio (OR) and corresponding 95 % confidence interval (95 % CI). RESULTS: A total number of six case-control studies including 638 SAH cases and 2,341 controls were identified. No association was found in dominant model or allele contrast genetic model (ε4 dominant model: OR = 1.06, 95 % CI = 0.91-1.25; ε3 dominant model: OR = 0.99, 95 % CI = 0.97-1.01; ε2 dominant model: OR = 0.99, 95 % CI = 0.78-1.25; ε4 versus ε3: OR = 1.14, 95 % CI = 0.96-1.35; ε4 versus ε2: OR = 1.07, 95 % CI = 0.90-1.28; ε3 versus ε2: OR = 1.00, 95 % CI = 0.96-1.04) for APOE polymorphism and SAH susceptibility. In the subgroup analyzed that was stratified by ethnicity, increased risk of SAH was found in Asian subjects when ε4 allele compared with ε3 allele (ε4 vs ε3, OR = 1.55, 95 % CI = 1.07-2.52). CONCLUSIONS: Our meta-analysis suggested that there is no association between APOE polymorphism and SAH risk for overall population. Due to several limitations in the present study, well-designed epidemiological studies with large sample size among different ethnicities should be performed in the future.

Automated synthesis of 18F-fluoropropoxytryptophan for amino acid transporter system imaging.

OBJECTIVE: This study was to develop a cGMP grade of [(18)F]fluoropropoxytryptophan ((18)F-FTP) to assess tryptophan transporters using an automated synthesizer. METHODS: Tosylpropoxytryptophan (Ts-TP) was reacted with K(18)F/kryptofix complex. After column purification, solvent evaporation, and hydrolysis, the identity and purity of the product were validated by radio-TLC (1M-ammonium acetate : methanol = 4 : 1) and HPLC (C-18 column, methanol : water = 7 : 3) analyses. In vitro cellular uptake of (18)F-FTP and (18)F-FDG was performed in human prostate cancer cells. PET imaging studies were performed with (18)F-FTP and (18)F-FDG in prostate and small cell lung tumor-bearing mice (3.7 MBq/mouse, iv). RESULTS: Radio-TLC and HPLC analyses of (18)F-FTP showed that the Rf and Rt values were 0.9 and 9 min, respectively. Radiochemical purity was >99%. The radiochemical yield was 37.7% (EOS 90 min, decay corrected). Cellular uptake of (18)F-FTP and (18)F-FDG showed enhanced uptake as a function of incubation time. PET imaging studies showed that (18)F-FTP had less tumor uptake than (18)F-FDG in prostate cancer model. However, (18)F-FTP had more uptake than (18)F-FDG in small cell lung cancer model. CONCLUSION: (18)F-FTP could be synthesized with high radiochemical yield. Assessment of upregulated transporters activity by (18)F-FTP may provide potential applications in differential diagnosis and prediction of early treatment response.