Gallic acid (GA), widely distributed in plants and feeds, is known to have a diverse range of activities such as anti-oxidant, anti-inflammatory, antibacterial, anti-allergic, anti-mutagenic, and ...anti-carcinogenic. The purpose of this study was to investigate the efficacy of inclusion of dietary GA at levels 0, 25, 50, 75, 100, or 150 mg/kg on growth performance, antioxidant status, and jejunum intestinal morphology of broiler chicks. In total, 630 one-day-old Arbor Acres (AA) male broiler chicks were randomly allotted to 6 treatment groups for a period of 6 weeks. The results indicate that dietary addition of GA at 75 to 100 mg/kg improved feed conversion efficiency in both the grower (d 21 to 42, P = 0.045) and overall (d 1 to 42, P = 0.026) periods. Dietary addition of GA at a concentration ≥100 mg/kg was able to exhibit higher breast muscle ratio at 42 d (P = 0.043). Interestingly, dietary GA inclusion level from 50 to 100 mg/kg reduced the crypt depth (P = 0.009) and increased the villus height:crypt depth ratio (VCR) of the birds (P = 0.006). Dietary supplementation of GA at 100 mg/kg decreased plasma malondialdehyde (MDA) content at 42 d of age (P = 0.030). Moreover, dietary addition of GA linearly increased plasma total antioxidant capacity (P = 0.039) and plasma total superoxide dismutase activities (P = 0.049) at 21 d of age. However, analysis of plasma biochemical markers revealed that dietary supplementation of GA did not exhibit beneficial health effects. Overall, we conclude that 75 to 100 mg/kg of GA are suitable for enhanced growth performance and health benefits in a broiler diet.
Abstract
The development of a vaccine to prevent congenital human cytomegalovirus (HCMV) disease is a public health priority. We tested rhesus CMV (RhCMV) prototypes of HCMV vaccine candidates in a ...seronegative macaque oral challenge model. Immunogens included a recombinant pentameric complex (PC; gH/gL/pUL128/pUL130/pUL131A), a postfusion gB ectodomain, and a DNA plasmid that encodes pp65-2. Immunization with QS21-adjuvanted PC alone or with the other immunogens elicited neutralizing titers comparable to those elicited by RhCMV infection. Similarly, immunization with all 3 immunogens elicited pp65-specific cytotoxic T-cell responses comparable to those elicited by RhCMV infection. RhCMV readily infected immunized animals and was detected in saliva, blood, and urine after challenge in quantities similar to those in placebo-immunized animals. If HCMV evades vaccine-elicited immunity in humans as RhCMV evaded immunity in macaques, a HCMV vaccine must elicit immunity superior to, or different from, that elicited by the prototype RhCMV vaccine to block horizontal transmission.
Rhesus CMV prototypes of HCMV vaccine candidates were tested in a seronegative macaque oral challenge model. Adjuvanted pentameric complex and postfusion gB subunits with pp65-2–encoding DNA elicited strong serum neutralizing and T-cell responses but were insufficient to prevent infection.
Pyrroloquinoline quinone (PQQ), a putative essential nutrient and redox modulator in microorganisms, cell and animal models, has been recognized as a growth promoter in rodents. Growth performance, ...carcass yield and antioxidant status were evaluated on broiler chickens fed different levels of PQQ disodium (PQQ.Na₂). A total of 784 day-old male Arbor Acres (AA) broilers were randomly allotted into seven dietary groups: negative control group (NC) fed a basal diet without virginiamycin (VIR) or PQQ.Na₂; a positive control group (PC) fed a diet with 15 mg of VIR/kg diet; and PQQ.Na₂ groups fed with 0.05, 0.10, 0.20, 0.40 or 0.80 mg PQQ.Na₂/kg diet. Each treatment contained eight replicates with 14 birds each. The feeding trial lasted for 6 weeks. The results showed that chicks fed 0.2 mg PQQ.Na₂/kg diet significantly improved growth performance comparable to those in PC group, and the feed efficiency enhancement effects of dietary PQQ.Na₂ was more apparent in grower phase. Dietary addition of PQQ.Na₂ had the potential to stimulate immune organs development, and low level dietary addition (<0.1 mg/kg) increased plasma lysozyme level. Broilers fed 0.2 mg PQQ.Na₂/kg diet gained more carcasses at day 42, and had lower lipid peroxide malondialdehyde content and higher total antioxidant power in plasma. The results indicated that dietary PQQ.Na₂ (0.2 mg/kg diet) had the potential to act as a growth promoter comparable to antibiotic in broiler chicks.
The potential benefits of supplementing pyrroloquinoline quinone disodium (PQQ·Na2) in the diet of broiler chicks were explored. We first examined the effect of different levels of dietary PQQ·Na2 on ...growth performance, carcass characteristics, and plasma biochemical parameters (trial 1). A total of 490 1-day-old male Arbor Acres (AA) broiler chicks were randomly divided into 5 dietary groups supplemented with 0, 0.05, 0.1, 0.2, or 0.4 mg PQQ·Na2/kg feed. As the 0.2 mg/kg PQQ·Na2 supplement gave the best performance, we then investigated whether this level of PQQ·Na2 influenced the redox status of plasma samples and mitochondrial-related metabolism (trial 2). A total of 120 1-day-old male AA chicks were randomly divided into 2 groups supplemented with 0 or 0.2 mg PQQ·Na2/kg diet. In trial 1, birds fed a diet containing 0.2 mg PQQ·Na2/kg showed lower feed conversion ratio compared with those fed the control diet in the overall study (d 1 to 42, P=0.039). Breast muscle yield (d 42) increased quadratically in response to dietary PQQ·Na2 supplementation (P=0.021). Analysis of plasma biochemical parameters revealed that feeding broiler chicks with ≤0.4 mg/kg PQQ·Na2 did not cause adverse health effects. In trial 2, birds fed 0.2 mg/kg PQQ·Na2 again showed improved feed efficiency than the control birds in the grower and overall phases (P=0.038 and 0.016, respectively). In addition, dietary PQQ·Na2 supplementation resulted in a higher anti-oxidative capacity (P=0.001), lower redox potential (P=0.008), and higher hepatic citrate synthase activity (P=0.002). In contrast, no difference in hepatic mitochondrial DNA copy number was observed between the 2 experimental groups (P>0.1). These results indicate that PQQ·Na2 is a potentially effective feed additive for improving feed efficiency, stimulating breast muscle development, and maintaining redox status in broiler chicks. Enhancement of mitochondria efficiency, rather than modulating mitochondria numbers, may underlie the growth-promoting effect of PQQ·Na2.
The protective effects of dietary pyrroloquinoline quinone disodium (PQQ.Na2) supplementation against oxidized sunflower oil-induced oxidative stress and liver injury in laying hens were examined. ...Three hundred and sixty 53-week-old Hy-Line Gray laying hens were randomly allocated into one of the five dietary treatments. The treatments included: (1) a diet containing 2% fresh sunflower oil; (2) a diet containing 2% thermally oxidized sunflower oil; (3) an oxidized sunflower oil diet with 100 mg/kg of added vitamin E; (4) an oxidized sunflower oil diet with 0.08 mg/kg of PQQ.Na2; and (5) an oxidized sunflower oil diet with 0.12 mg/kg of PQQ.Na2. Birds fed the oxidized sunflower oil diet showed a lower feed intake compared to birds fed the fresh oil diet or oxidized oil diet supplemented with vitamin E (P=0.009). Exposure to oxidized sunflower oil increased plasma malondialdehyde (P<0.001), hepatic reactive oxygen species (P<0.05) and carbonyl group levels (P<0.001), but decreased plasma glutathione levels (P=0.006) in laying hens. These unfavorable changes induced by the oxidized sunflower oil diet were modulated by dietary vitamin E or PQQ.Na2 supplementation to levels comparable to the fresh oil group. Dietary supplementation with PQQ.Na2 or vitamin E increased the activities of total superoxide dismutase and glutathione peroxidase in plasma and the liver, when compared with the oxidized sunflower oil group (P<0.05). PQQ.Na2 or vitamin E diminished the oxidized sunflower oil diet induced elevation of liver weight (P=0.026), liver to BW ratio (P=0.001) and plasma activities of alanine aminotransferase (P=0.001) and aspartate aminotransferase (P<0.001) and maintained these indices at the similar levels to the fresh oil diet. Furthermore, oxidized sunflower oil increased hepatic DNA tail length (P<0.05) and tail moment (P<0.05) compared with the fresh oil group. Dietary supplementation of PQQ.Na2 or vitamin E decreased the oxidized oil diet induced DNA tail length and tail moment to the basal levels in fresh oil diet. These results indicate that PQQ.Na2 is a potential antioxidant and is as effective against oxidized oil-related liver injury in laying hens as vitamin E. The protective effects of PQQ.Na2 against liver damage induced by oxidized oil may be partially due to its role in the scavenging of free radicals, inhibiting of lipid peroxidation and enhancing of antioxidant defense systems.
Fluorescence (excitation-emission matrices, EEMs) spectroscopy coupled with PARAFAC (parallel factor) modelling and UV-Vis (ultraviolet visible) spectra were used to ascertain the sources, ...distribution and biogeochemical transformation of dissolved organic matter (DOM) in the Duliujian River catchment. Dissolved organic carbon (DOC), chromophoric dissolved organic matter (a335) (CDOM), and hydrophobic components (a260) were higher in summer than in other seasons with 53.3 m−1, while aromaticity (SUVA254) was higher in spring. Four fluorescent components, namely terrestrial humic acid (HA)-like (A/C), terrestrial fulvic acid (FA)-like (A/M), autochthonous fulvic acid (FA)-like (A/M), and protein-like substances (Tuv/T), were identified using EEM-PARAFAC modelling in this river catchment. The results demonstrated that terrestrial HA-like substances enhance its contents in summer ARE compared with BRE, whilst terrestrial FA-like substances were newly input in summer ARE, which was entirely absent upstream and downstream, suggesting that rain events could significantly input the terrestrial soil-derived DOM in the ambient downward catchments. Autochthonous FA-like substances in summer BRE could derive from phytoplankton in the downstream waters. The results also showed that DOM from wetland exhibited lower fluorescent intensity of humic-like peak A/C and fulvic-like peak A/M, molecular weight (SR) and humification index (HIX) during the low-flow season. Built-up land, cropland, and unused land displayed higher a335 (CDOM). A higher proportion of forest and industrial land in the SCs showed higher SUVA254 values. Humic-like moiety, molecular weight and aromaticity were more responsive to land use during stormflow in summer. Rainfall could increase the export of soil DOM from cropland and unused land, which influences the spatial variation of HIX. The results in this study highlighted that terrestrial DOM has a significant influence on the biogeochemical alterations of DOM compositions and thus water quality in the downward watershed catchments, which might significantly vary according to the land-use types and their alterations by human activities.
The development of digital cancer twins relies on the capture of high-resolution representations of individual cancer patients throughout the course of their treatment. Our research aims to improve ...the detection of metastatic disease over time from structured radiology reports by exposing prediction models to historical information. We demonstrate that Natural language processing (NLP) can generate better weak labels for semi-supervised classification of computed tomography (CT) reports when it is exposed to consecutive reports through a patient's treatment history. Around 714,454 structured radiology reports from Memorial Sloan Kettering Cancer Center adhering to a standardized departmental structured template were used for model development with a subset of the reports included for validation. To develop the models, a subset of the reports was curated for ground-truth: 7,732 total reports in the lung metastases dataset from 867 individual patients; 2,777 reports in the liver metastases dataset from 315 patients; and 4,107 reports in the adrenal metastases dataset from 404 patients. We use NLP to extract and encode important features from the structured text reports, which are then used to develop, train, and validate models. Three models-a simple convolutional neural network (CNN), a CNN augmented with an attention layer, and a recurrent neural network (RNN)-were developed to classify the type of metastatic disease and validated against the ground truth labels. The models use features from consecutive structured text radiology reports of a patient to predict the presence of metastatic disease in the reports. A single-report model, previously developed to analyze one report instead of multiple past reports, is included and the results from all four models are compared based on accuracy, precision, recall, and F1-score. The best model is used to label all 714,454 reports to generate metastases maps. Our results suggest that NLP models can extract cancer progression patterns from multiple consecutive reports and predict the presence of metastatic disease in multiple organs with higher performance when compared with a single-report-based prediction. It demonstrates a promising automated approach to label large numbers of radiology reports without involving human experts in a time- and cost-effective manner and enables tracking of cancer progression over time.
Id1 is a helix-loop-helix transcriptional modulator that increases the aggressiveness of malignant glial neoplasms. Since most glioblastomas (GBMs) show increased phosphatidylinositol-3 kinase ...(PI-3K) signaling, we sought to determine whether this pathway regulates Id1 expression. Higher basal Id1 expression correlates with dysregulated PI-3K signaling in multiple established GBM cell lines. Further characterization of PI-3K-dependent Id1 regulation reveals that chemical or genetic inhibition of PI-3K signaling reduces Id1 protein but not mRNA expression. Overall, PI-3K signaling appears to enhance Id1 translation with no significant effect on its stability. PI-3K signaling is known to regulate protein translation through mTORC1-dependent phosphorylation of 4E-BP1, which reduces its association with and inhibition of the translation initiation factor eIF4E. Interestingly, while inhibition of PI-3K and AKT lowers 4E-BP1 phosphorylation and expression of Id1 in all cases, inhibition of TORC1 with rapamycin does not consistently have a similar effect, suggesting an alternative mechanism for PI-3K-dependent regulation of Id1 translation. We now identify a potential role for the serine-threonine phosphatase PPM1G in translational regulation of Id1 protein expression. PPM1G knockdown by siRNA increase both 4E-BP1 phosphorylation and Id1 expression and PPM1G and 4E-BP1 co-associates in GBM cells. Furthermore, PPM1G is a phosphoprotein and this phosphorylation appears to be regulated by PI-3K activity. Finally, PI-3K inhibition increases PPM1G activity when assessed by an in vitro phosphatase assay. Our findings provide the first evidence that the PI-3K/AKT signaling pathway modulates PPM1G activity resulting in a shift in the balance between hyper- and hypo-phosphorylated 4E-BP1 and translational regulation of Id1 expression.
Hepatocellular carcinoma (HCC) is a common primary cancer associated frequently with hepatitis C virus (HCV). To gain insight into the molecular mechanisms of hepatocarcinogenesis, and to identify ...potential HCC markers, we performed cDNA microarray analysis on surgical liver samples from 20 HCV-infected patients. RNA from individual tumors was compared with RNA isolated from adjacent nontumor tissue that was cirrhotic in all of the cases. Gene expression changes related to cirrhosis were filtered out using experiments in which pooled RNA from HCV-infected cirrhotic liver without tumors was compared with pooled RNA from normal liver. Expression of approximately 13,600 genes was analyzed using the advanced analysis tools of the Rosetta Resolver System. This analysis revealed a set of 50 potential HCC marker genes, which were up-regulated in the majority of the tumors analyzed, much more widely than common clinical markers such as cell proliferation-related genes. This HCC marker set contained several cancer-related genes, including serine/threonine kinase 15 (STK15), which has been implicated in chromosome segregation abnormalities but which has not been linked previously with liver cancer. In addition, a set of genes encoding secreted or plasma proteins was identified, including plasma glutamate carboxypeptidase (PGCP) and two secreted phospholipases A2 (PLA2G13 and PLA2G7). These genes may provide potential HCC serological markers because of their strong up-regulation in more than half of the tumors analyzed. Thus, high throughput methods coupled with high-order statistical analyses may result in the development of new diagnostic tools for liver malignancies.
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