Laetiporus sulphureus-fermented wheat bran enhanced the broiler growth performance by improving the intestinal microflora and inflammation status.

This study investigates the effects of Laetiporus sulphureus-fermented wheat bran (LS) as a feed supplementation on the immunomodulative properties in broiler chickens. Crude phenolic compounds, crude polysaccharides, crude triterpenoids, and ergosterol were determined in LS water extracts. In animal experiments, 400 male broilers (Ross 308) were randomly assigned into 5 groups fed with a corn-soybean-based diet (control) and a control diet replaced with 5% wheat bran (WB), 10% WB, 5% LS, and 10% LS, respectively. Each group had 4 replicates and 20 birds per pen (total of 80 birds/treatment). The results showed that the 5% LS-supplemented group had significantly higher BW in the finisher phase (22-35 D). Better feed conversion ratio (P < 0.05) of LS-supplemented groups was observed in both the finisher phase and the overall experimental period. The LS-supplemented groups had significantly lower coliform counts in the ileum than the other treatment and control groups (P < 0.05). The results of serum immunoglobulin showed that LS supplementation significantly increased serum IgA concentration compared with the control and WB-supplemented groups (P < 0.05). Simultaneously, ileal IgA contents of the LS groups were significantly higher than in the WB and control groups (P < 0.05). Regarding proinflammatory cytokines, serum tumor necrosis factor alpha and IL-6 in the LS-supplemented groups were significantly lower than those in the 10% WB group (P < 0.05), whereas serum tumor necrosis factor alpha and IL-1ß in the 5% LS group were significantly lower than in both the control and WB-supplemented groups (P < 0.05). An investigation on the effects of LS on immune-related genes in broiler showed that chickens supplemented with 5% LS had lower levels of liver and jejunum IL-1ß and NF-κB mRNA compared with the control group and WB groups (P < 0.05). In conclusion, LS supplementation can potentially enhance growth performance of broilers by improving intestinal microflora and inflammation status.

Effect of Cobalt Precursors on Cobalt-Hydroxyapatite Used in Bone Regeneration and MRI.

In clinical dentistry practice, supplemental bone surgery or jawbone defect after tooth extraction must be assisted by a bone-filling material. Cobalt-substituted hydroxyapatite (COHA) effectively promotes bone cell growth, reduces the inflammatory response, and is an antibacterial agent. COHA can therefore be used as an alveolar bone-filling material or guided bone regeneration membrane. Meanwhile, COHA can be used in magnetic resonance imaging (MRI) with negative contrast agents and targeting materials without causing metal interference with the image. Hence, COHA has received increasing amounts of attention in recent years. However, the influence of different cobalt precursors on the synthesized COHA is still unknown. Therefore, COHA synthesized from 3 cobalt precursors (cobalt chloride, cobalt nitrate, and cobalt sulfate) was compared in this study. The results show that COHA synthesized by the precursor with the smallest anion radius, cobalt chloride, has a larger particle size (239 nm) and a higher cobalt ion substitution rate (15.6%). When the cobalt ion substitution rate increases, the MRI has a stronger contrast. Bioactivity data indicate that COHAC is more susceptible to degradation and therefore releases more cobalt ions to contribute to the differentiation of bone cells. Based on these studies, COHAC prepared with the cobalt chloride precursor has a higher cobalt ion substitution rate, faster degradation rate, better image contrast, and better bioactivity. It is therefore the preferred choice of bone-filling material for alveolar bone regeneration.

Effects of dietary Antrodia cinnamomea fermented product supplementation on metabolism pathways of antioxidant, inflammatory, and lipid metabolism pathways-a potential crosstalk.

OBJECTIVE: This study was conducted to fathom the underlying mechanisms of nutrition intervention and redox sensitive transcription factors regulated by Antrodia cinnamomea fermented product (FAC) dietary supplementation in broiler chickens. METHODS: Four hundreds d-old broilers (41±0.5 g/bird) assigned to 5 groups were examined after consuming control diet, or control diet replaced with 5% wheat bran (WB), 10% WB, 5% FAC, and 10% FAC. Liver mRNA expression of antioxidant, inflammatory and lipid metabolism pathways were analyzed. Prostaglandin E2 (PGE2) concentration in each group were tested in the chicken peripheral blood mononuclear cells (cPBMCs) of 35-d old broilers to represent the stress level of the chickens. Furthermore, these cells were stimulated with 2,2'-Azobis(2-amidinopropane) dihydrochloride (AAPH) and lipopolysaccharide (LPS) to evaluate the cell stress tolerance by measuring cell viability and oxidative species. RESULTS: Heme oxygenase-1, glutathione S-transferase, glutamate-cysteine ligase, catalytic subunit, and superoxide dismutase, and nuclear factor (erythroid-derived 2)-like 2 (Nrf2) that regulates the above antioxidant genes were all up-regulated significantly in FAC groups. Reactive oxygen species modulator protein 1 and NADPH oxygenase 1 were both rather down-regulated in 10% FAC group as comparison with two WB groups. Despite expressing higher level than control group, birds receiving diet containing FAC had significantly lower expression level in nuclear factor-kappa B (NF-κB) and other genes (inducible nitric oxide synthase, tumor necrosis factor-α, interleukin-1ß, nucleotide-binding domain, leucine-richcontaining family, pyrin domain-containing-3, and cyclooxygenase 2) involving in inflammatory pathways. Additionally, except for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase that showed relatively higher in both groups, the WB, lipoprotein lipase, Acetyl-CoA carboxylase, fatty acid synthase, fatty acid binding protein, fatty acid desaturase 2 and peroxisome proliferator-activated receptor alpha genes were expressed at higher levels in 10% FAC group. In support of above results, promoted Nrf2 and inhibited NF-κB nuclear translocation in chicken liver were found in FAC containing groups. H2O2 and NO levels induced by LPS and AAPH in cPBMCs were compromised in FAC containing diet. In 35-d-old birds, PGE2 production in cPBMCs was also suppressed by the FAC diet. CONCLUSION: FAC may promote Nrf2 antioxidant pathway and positively regulate lipid metabolism, both are potential inhibitor of NF-κB inflammatory pathway.

Autonomic dysfunction as an independent risk factor for uncontrolled inflammation in chronic rhinosinusitis following functional endoscopic sinus surgery.

BACKGROUND: Chronic rhinosinusitis (CRS) is a multi-factorial disorder that causes systemic symptoms beyond rhinologic symptoms alone. A possible association between autonomic nervous system (ANS) dysfunction and CRS has been identified; however, few studies have confirmed this observation. In this study, we prospectively measured changes in ANS dysfunction symptoms following functional endoscopic sinus surgery (FESS) and explored the impact of ANS dysfunction on surgical outcomes of CRS. METHODOLOGY: Patients diagnosed with CRS who consented to surgical intervention were included prospectively. All patients completed the Sino-nasal Outcome Test-22 (SNOT-22) and the 31-item Composite Autonomic Symptom Score (COMPASS 31) questionnaires before the operation and during the follow-up period. Clinical demographic data, Lund-Mackay, and modified Lund-Kennedy scores were recorded and measured. RESULTS: A total of 102 patients were enrolled. The median SNOT-22 and COMPASS 31 scores significantly improved following FESS from 43.0 to 14.0 and 21.0 to 11.2 (all P less than 0.001), respectively. FESS led to a significant reduction in the prevalence of various ANS dysfunction symptoms. In multivariate analyses, revision surgeries (odds ratio [OR] 5.012, 95% confidence interval [CI] 1.52416.489; P=0.008), CRS with nasal polyps (OR 4.071, 95% CI 1.454-11.40; P=0.008), and higher Pre-FESS COMPASS 31 scores (OR 1.043, 95% CI 1.003-1.084; P=0.036) were independent risk factors for uncontrolled inflammation following FESS. CONCLUSIONS: ANS dysfunction symptoms are prevalent in CRS and higher preoperative COMPASS 31 scores correspond with poor surgical outcomes. Following FESS, the majority of ANS dysfunction symptoms can be alleviated. Further investigations are required to explore the possible mechanism of how ANS is involved in the pathogenesis of CRS.

Computational fluid dynamic simulations of a cavopulmonary assist device for failing Fontan circulation.

OBJECTIVES: Adult patients who have undergone the Fontan procedure are highly vulnerable to gradual, progressive circulatory failure, and options to reverse this situation are few. A cavopulmonary assist device could decongest the venous and lymphatic systems, overcome elevated pulmonary vascular resistance, increase cardiac output, and support some of these patients to heart transplant. This study characterizes the performance and challenges of a novel multilumen cannula coupled to an external blood pump proposed as a potential Fontan cavopulmonary assist strategy. METHODS: Computational fluid dynamic simulations were conducted for 3 extracardiac Fontan geometries consisting of 1 idealized model and 2 patient-specific models. A range of physiologic flow rates and pump assist levels were simulated to calculate the pressure gain provided by the multilumen cannula. Hemolysis index was estimated for the idealized model with Lagrangian particle tracking and 2 variations of the power-law. Wall shear stresses were also examined. RESULTS: Pressure gains up to 4 and 9 mm Hg were achieved for the idealized and patient-specific models, respectively. Pressure gains increased with both higher cardiac output and larger pump intake through the external pump. Flow-weighted hemolysis show hemoglobin damage levels to be several times lower than the 2% threshold at the highest pump intake flow cases. Wall shear stress predictions depict elevated areas in the pulmonary vessels and regions of the cannula device. CONCLUSIONS: The cannula tested in this study shows promise as a percutaneous option to bridge support in some patients with a failing extracardiac Fontan. Limitations identified will be addressed in future design iterations and in ongoing experimental tests.

Evaluation of potential antioxidant and anti-inflammatory effects of Antrodia cinnamomea powder and the underlying molecular mechanisms via Nrf2- and NF-κB-dominated pathways in broiler chickens.

Antrodia cinnamomea, a precious and unique medical fungus existing exclusively in Taiwan, exhibits antioxidant and immunomodulatory properties. This study was conducted to evaluate the beneficial effects of A. cinnamomea powder (ACP) and to further illuminate its underlying antioxidant and immunomodulation molecular mechanisms in broilers. The functional compounds of ACP-crude triterpenoids, crude polysaccharides, and total phenolic content-were assayed, respectively. Two-hundred-forty one-day-old broilers (Ross 308) were assigned to 4 treatment groups receiving dietary supplementation with ACP at 0, 0.1, 0.2, and 0.4% for 35 days. Each group had 4 replicate pens, with 15 birds per pen. During 1 to 21- and 22 to 35-day periods, chickens on ACP-supplemented diet demonstrated increased body weight gain, compared to those on the control diet, resulting in increased weight gain throughout the entire experimental period with an increased tendency in feed consumption yet no significant difference in FCR. Blood antioxidant potentiality, superoxide dismutase (SOD), increased in birds fed the supplemented diet at both 21 and 35 d, accompanied by higher catalase (CAT) activity at 21 days. In vivo peripheral blood mononuclear cells (PBMC) exposed to lipopolysaccharide (LPS) and 2,2΄-Azobis(2-amidinopropane) dihydrochloride (AAPH) capability showed that the diminished cell viability caused by both challenge factors was improved in ACP-supplemented groups. Antioxidant genes dominated by Nrf2 genes, such as HO-1 and GCLC, were up-regulated in 35-day-old birds. Inflammatory-related genes, such as IL-1ß and IL-6, ruled mainly by NF-κB, were rather down-regulated by 0.2% ACP addition at 21 and 35 days. Protein expression of Nrf2 and NF-κB in the liver supported the mRNA results, demonstrating that all ACP-supplemented groups showed significantly higher Nrf2 expression, whereas the NF-κB was inhibited. In conclusion, preferable microbial balance may putatively indicate the improvement of immunomodulatory-related capacity by ACP. Furthermore, ACP could induce the Nrf2-dependent pathway and decrease the NF-κB-dominated inflammatory signaling pathway. Antioxidant and immune capacity in terms of antioxidant enzymes and cell tolerance also was elevated by ACP. Concomitantly, body weight increasing with ACP supplementation as compared to the corresponding control group further implied the promising effects exerted by ACP.

The symptom burden of autonomic dysfunction is positively associated with chronic rhinosinusitis status.

BACKGROUND: Dysregulation of the autonomic system can affect sinonasal physiological function and may exacerbate the symptom burden associated with rhinosinusitis. However, the association between autonomic dysfunction and chronic rhinosinusitis (CRS) has seldom been studied. Here, we investigated the relationship between autonomic dysfunction and CRS. METHODS: Patients with CRS who failed medical treatment were prospectively enrolled. All patients underwent pre-operative examinations and completed questionnaires, including the reflux symptom index (RSI) and the Sino-nasal Outcome Test-22 (SNOT-22). Autonomic dysfunction was scored using the 31-item Composite Autonomic Symptom Score (COMPASS 31), a validated simple instrument used to evaluate dysautonomia. RESULTS: We prospectively enrolled a total of 89 CRS patients, including 37 with polyps (CRSwNP) and 52 without polyps (CRSsNP). The most common dysautonomic symptoms were dry eye, dry mouth, postural dizziness, and a sensation of excessive fullness after meals. Significant positive correlations were evident between COMPASS 31 and SNOT-22 scores in CRSwNP patients. CRS-associated symptoms, including cough, post-nasal drip, sleep, and psychological dysfunction, were correlated with the level of autonomic dysfunction. CONCLUSIONS: We found a positive correlation between the symptom burdens of autonomic dysfunction and CRSwNP. The relationship between autonomic dysfunction and CRS is highly complex; further work is needed.

[First aid system for trauma: development and status].

With the great progress of the economy, the level of industrialization has been increasing year by year, which leads to an increase in accidental trauma accidents. Chinese annual death of trauma is already more than 400 000, which makes trauma the fifth most common cause of death, following malignant tumor, heart, brain and respiratory diseases. Trauma is the leading cause of the death of young adults. At the same time, trauma has become a serious social problem in peace time. Trauma throws great treats on human health and life. As an important part in the medical and social security system, the emergency of trauma system occupies a very important position in the emergency medical service system. In European countries as well as the United States and also many other developed countries, trauma service system had a long history, and progressed to an advanced stage. However, Chinese trauma service system started late and is still developing. It has not turned into a complete and standardized system yet. This review summarizes the histories and current situations of the development of traumatic first aid system separately in European countries, the United States and our country. Special attentions are paid to the effects of the pre- and in-hospital emergency care. We also further try to explore the Chinese trauma emergency model that adapts to the situations of China and characteristics of different regions of China. Our review also introduces the trauma service system that suits the situations of China proposed by Professor Jiang Baoguo's team in details, taking Chinese conditions into account, they conducted a thematic study and made an expert consensus on pre-hospital emergency treatment of severe trauma, providing a basic routine and guidance of severe trauma treatment for those pre-hospital emergency physicians. They also advised to establish independent trauma disciplines and trauma specialist training systems, and to build the regional trauma care system as well as the standards for graded treatment, thus establishing a multiple disciplinary team (MDT) of severe trauma. In this way, we can reduce the mortality and disability risks of severe trauma, improve the quality of patients' life, and save more lives.

Antioxidant capacity of phytochemicals and their potential effects on oxidative status in animals - A review.

Oxidative stress suppresses animal health, performance, and production, subsequently impacting economic feasibility; hence, maintaining and improving oxidative status especially through natural nutrition strategy are essential for normal physiological process in animals. Phytochemicals are naturally occurring antioxidants that could be considered as one of the most promising materials used in animal diets in various forms. In this review, their antioxidant effects on animals are discussed as reflected by improved apparent performance, productivity, and the internal physiological changes. Moreover, the antioxidant actions toward animals further describe a molecular basis to elucidate their underlying mechanisms targeting signal transduction pathways, especially through the antioxidant response element/nuclear factor (erythroid-derived 2)-like 2 transcription system.

Comparison of PI-RADS 2, ADC histogram-derived parameters, and their combination for the diagnosis of peripheral zone prostate cancer.

PURPOSE: The purpose of this study was to compare the PI-RADS V2 scores, ADC histogram-derived parameters, and their combination for the diagnosis of clinically significant peripheral zone prostate cancer (PCa). MATERIALS AND METHODS: The IRB approved this retrospective study of 47 men who underwent 1.5 Tesla endorectal prostate magnetic resonance imaging (MRI). Informed consent was waived. Two readers identified and scored MRI lesions using PI-RADS V2. Their mean, median, 10th, 25th, 75th percentile ADC values, and normalized ratio were also calculated. Multilevel logistic regression and receiver-operating characteristic (ROC) curve analyses assessed their diagnostic performance. Clinically significant PCa was defined as tumor volume over 0.5 cc and Gleason grade of 4 or 5 on prostatectomy. RESULTS: The area under the ROC curve (A z) of the overall and diffusion-weighted imaging (DWI) PI-RADS V2 scores were 0.69 and 0.84 (reader-1), and 0.68 and 0.73 (reader-2). The A z of ADC parameters ranged from 0.68 to 0.75 for both readers. Compared to other predictors, DWI PI-RADS V2 yielded the highest A z for identification of significant cancer; but, except for reader-1 75th percentile ADC, the differences were not statistically significant (P > 0.05). Adding ADC parameters to PI-RADS V2 scores did not improve their diagnostic ability. CONCLUSION: DWI PI-RADS V2 score may a better predictor of clinically significant PCa than the overall PI-RADS V2 score, but its diagnostic performance was not significantly improved by the addition of objective ADC value measurements.

Candidate tumor suppressor B-cell translocation gene 3 impedes neoplastic progression by suppression of AKT.

BTG3 (B-cell translocation gene 3) is a p53 target that also binds and inhibits E2F1. Although it connects two major growth-regulatory pathways functionally and is downregulated in human cancers, whether and how BTG3 acts as a tumor suppressor remain largely uncharacterized. Here we present evidence that BTG3 binds and suppresses AKT, a kinase frequently deregulated in cancers. BTG3 ablation results in increased AKT activity that phosphorylates and inhibits glycogen synthase kinase 3ß. Consequently, we also observed elevated ß-catenin/T-cell factor activity, upregulation of mesenchymal markers, and enhanced cell migration. Consistent with these findings, BTG3 overexpression suppressed tumor growth in mouse xenografts, and was associated with diminished AKT phosphorylation and reduced ß-catenin in tissue specimens. Significantly, a short BTG3-derived peptide was identified, which recapitulates these effects in vitro and in cells. Thus, our study provides mechanistic insights into a previously unreported AKT inhibitory pathway downstream of p53. The identification of an AKT inhibitory peptide also unveils a new avenue for cancer therapeutics development.

Predicting cancer risks from dental computed tomography.

Dental computed tomography (CT) has become a common tool when carrying out dental implants, yet there is little information available on its associated cancer risk. The objective of this study was to estimate the lifetime-attributable risk (LAR) of cancer incidence that is associated with the radiation dose from dental CT scans and to evaluate the effect of scan position, sex, and age on the cancer risk. This retrospective cohort study involved 505 participants who underwent CT scans. The mean effective doses for male and female patients in the maxilla group were 408 and 389 µSv (P = 0.055), respectively, whereas the mean effective doses for male and female patients in the mandible groups were 475 and 450 µSv (P < 0.001), respectively. The LAR for cancer incidence after mandible CT scanning varied from 1 in 16,196 for a 30-y-old woman to 1 in 114,680 for a 70-y-old man. The organ-specific cancer risks for thyroid cancer, other cancers, leukemia, and lung cancer account for 99% of the LAR. Among patients of all ages, the estimated LAR of a mandible scan was higher than that of a maxilla scan. Furthermore, the LAR for female thyroid cancer had a peak before age 45 y. The risk for a woman aged 30 y is roughly 8 times higher than that of a woman aged 50 y. After undergoing a dental CT scan, the possible cancer risks related to sex and age across various different anatomical regions are not similar. The greatest risk due to a dental CT scan is for a mandible scan when the woman is younger than 45 y. Given the limits of the sample size, machine parameters, and the retrospective nature of this study, the results need to be interpreted within the context of this patient population. Future studies will be of value to corroborate these findings.

Helicobacter pylori sensitizes TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in human gastric epithelial cells through regulation of FLIP.

Helicobacter pylori (H. pylori) infection is associated with chronic gastritis, peptic ulcer and gastric cancer. Apoptosis induced by microbial infections is implicated in the pathogenesis of H. pylori infection. Here we show that human gastric epithelial cells sensitized to H. pylori confer susceptibility to TRAIL-mediated apoptosis via modulation of death receptor signaling. Human gastric epithelial cells are intrinsically resistant to TRAIL-mediated apoptosis. The induction of TRAIL sensitivity by H. pylori is dependent on the activation of caspase-8 and its downstream pathway. H. pylori induces caspase-8 activation via enhanced assembly of the TRAIL death-inducing signaling complex (DISC) through downregulation of cellular FLICE-inhibitory protein (FLIP). Overexpression of FLIP abolished the H. pylori-induced TRAIL sensitivity in human gastric epithelial cells. Our study thus demonstrates that H. pylori induces sensitivity to TRAIL apoptosis by regulation of FLIP and assembly of DISC, which initiates caspase activation, resulting in the breakdown of resistance to apoptosis, and provides insight into the pathogenesis of gastric damage in Helicobacter infection. Modulation of host apoptosis signaling by bacterial interaction adds a new dimension to the pathogenesis of Helicobacter.

MicroRNA-17-5p post-transcriptionally regulates p21 expression in irradiated betel quid chewing-related oral squamous cell carcinoma cells.

BACKGROUND AND PURPOSE: Betel nut chewing is associated with oral cavity cancer in Taiwan. OC3 is an oral carcinoma cell line that was established from cells collected from a long-term betel nut chewer who does not smoke. After we found that microRNA-17-5p (miR-17-5p) is induced in OC3 cells, we used this cell line to examine the biological role(s) of this microRNA in response to exposure to ionizing radiation. MATERIALS AND METHODS: A combined SYBR green-based real-time PCR and oligonucleotide ligation assay was used to examine the expression of the miR-17 polycistron in irradiated OC3 cells. The roles of miR-17-5p and p21 were evaluated with specific antisense oligonucleotides (ODN) that were designed and used to inhibit their expression. Expression of the p21 protein was evaluated by Western blotting. The clonogenic assay and annexin V staining were used to evaluate cell survival and apoptosis, respectively. Cells in which miR-17-5p was stably knocked down were used to create ectopic xenografts to evaluate in vivo the role of miR-17-5p. RESULTS: A radiation dose of 5 Gy significantly increased miR-17-5p expression in irradiated OC3 cells. Inhibition of miR-17-5p expression enhanced the radiosensitivity of the OC3 cells. We found that miR-17-5p downregulates radiation-induced p21 expression in OC3 cells and, by using a tumor xenograft model, it was found that p21 plays a critical role in increasing the radiosensitivity of OC3 cells in vitro and in vivo. CONCLUSION: miR-17-5p is induced in irradiated OC3 cells and it downregulates p21 protein expression, contributing to the radioresistance of OC3 cells.