Dietary isoleucine supplementation enhances growth performance, modulates the expression of genes related to amino acid transporters and protein metabolism, and gut microbiota in yellow-feathered chickens.

This study investigated the effects of dietary isoleucine (Ile) on growth performance, intestinal expression of amino acid transporters, protein metabolism-related genes and intestinal microbiota in starter phase Chinese yellow-feathered chickens. Female Xinguang yellow-feathered chickens (n = 1,080, aged 1 d) were randomly distributed to 6 treatments, each with 6 replicates of 30 birds. Chickens were fed diets with 6 levels of total Ile (6.8, 7.6, 8.4, 9.2, 10.0, and 10.8 g/kg) for 30 d. The average daily gain and feed conversion ratio were improved with dietary Ile levels (P < 0.05). Plasma uric acid content and glutamic-oxalacetic transaminase activity were linearly and quadratically decreased with increasing dietary Ile inclusion (P < 0.05). Dietary Ile level had a linear (P < 0.05) or quadratic (P < 0.05) effect on the jejunal expression of ribosomal protein S6 kinase B1 and eukaryotic translation initiation factor 4E binding protein 1. The relative expression of jejunal 20S proteasome subunit C2 and ileal muscle ring finger-containing protein 1 decreased linearly (P < 0.05) and quadratically (P < 0.05) with increasing dietary Ile levels. Dietary Ile level had a linear (P = 0.069) or quadratic (P < 0.05) effect on the gene expression of solute carrier family 15 member 1 in jejunum and solute carrier family 7 member 1 in ileum. In addition, bacterial 16S rDNA full-length sequencing showed that dietary Ile increased the cecal abundances of the Firmicutes phylum, and Blautia, Lactobacillus, and unclassified_Lachnospiraceae genera, while decreased that of Proteobacteria, Alistipes, and Shigella. Dietary Ile levels affected growth performance and modulated gut microbiota in yellow-feathered chickens. The appropriate level of dietary Ile can upregulate the expression of intestinal protein synthesis-related protein kinase genes and concomitantly inhibit the expression of proteolysis-related cathepsin genes.

Genistein improves the reproductive performance and bone status of breeder hens during the late egg-laying period.

Genistein (GEN), a type of soy isoflavones, is similar to estrogen structurally and functionally. The effects of dietary gen on the reproductive performance and bone status of breeder hens were investigated. A total pf 720 laying broiler breeder (LBB) hens were randomly allocated into 3 groups with supplemental dietary GEN doses (0, 40, 400 mg/kg). Each treatment has 8 replicates of 30 birds. The results indicated that supplemental GEN significantly improved the egg production and eggshell strength of LBB hens. Dietary GEN was deposited into the egg yolk, which decreased malonaldehyde in the follicle and egg yolk. The levels of vitellogenin (VTG), progesterone, and follicle-stimulating hormone in the serum of GEN-treated groups were elevated compared with the control group. Furthermore, GEN treatment downregulated the mRNA expression of insulin-like growth factor binding protein in the fallopian tube, whereas 40 mg/kg GEN treatment upregulated estrogen receptor α expression. Both the mRNA expression of VTG-II in the liver and mRNA expression of amphiregulin in the fallopian tube were upregulated after 40 and 400 mg/kg GEN treatment. In the 400 mg/kg GEN-treated group, the levels of calcitonin and alkaline phosphatase in the serum were increased compared with the control group, which was consistent with the increased levels of calcium and phosphorus in the tibia. Supplemental GEN (400 mg/kg) improved the tibia strength of LBB hens, whereas 40 mg/kg GEN had better effects on laying performance. In summary, dietary GEN could improve the egg production and quality, as well as the bone status of LBB hens during the late egg-laying period.

Effects of curcumin on performance, antioxidation, intestinal barrier and mitochondrial function in ducks fed corn contaminated with ochratoxin A.

Curcumin has been attributed with antioxidant, anti-inflammatory, antibacterial activities, and has shown highly protective effects against enteropathogenic bacteria and mycotoxins. Ochratoxin A (OTA) is one of the major intestinal pathogenic mycotoxins. The possible effect of curcumin on the alleviation of enterotoxicity induced by OTA is unknown. The effects of dietary curcumin supplementation on OTA-induced oxidative stress, intestinal barrier and mitochondrial dysfunctions were examined in young ducks. A total of 540 mixed-sex 1-day-old White Pekin ducklings with initial BW (43.4±0.1 g) were randomly assigned into controls (fed only the basal diet), a group fed an OTA-contaminated diet (2 mg/kg feed), and a group fed the same OTA-contaminated feed plus 400 mg/kg of curcumin. Each treatment consisted of six replicates, each containing 30 ducklings and treatment lasted for 21 days. There was a significant decrease in average daily gain (ADG) and increased feed : gain caused by OTA (P<0.05); curcumin co-treatment prevented the decrease in BW and ADG compared with the OTA group (P<0.05). Histopathological and ultrastructural examination showed clear signs of enterotoxicity caused by OTA, but these changes were largely prevented by curcumin supplementation. Curcumin decreased the concentrations of interleukin-1ß, tumor necrosis factor-α and malondialdehyde, and increased the activity of glutathione peroxidase induced by OTA in the jejunal mucosa of ducks (P<0.05). Additionally, curcumin increased jejunal mucosa occludin and tight junction protein 1 mRNA and protein levels, and decreased those of ρ-associated protein kinase 1 (P<0.05). Notably, curcumin inhibited the increased expression of apoptosis-related genes, and downregulated mitochondrial transcription factors A, B1 and B2 caused by OTA without any effects on RNA polymerase mitochondrial (P<0.05). These results indicated that curcumin could protect ducks from OTA-induced impairment of intestinal barrier function and mitochondrial integrity.

Dietary curcumin enhances intestinal antioxidant capacity in ducklings via altering gene expression of antioxidant and key detoxification enzymes.

The study investigated the effects of dietary curcumin supplementation on tissue distribution of curcumin and its metabolites, intestinal antioxidant capacity, and expression of detoxification-related genes in ducks. A total of 720 one-day-old male Cherry Valley Pekin ducklings (initial BW 58.6 ± 0.1 g) were randomly assigned to 4 dietary groups each with 6 replicates of 30 ducks using a single factorial arrangement design. Ducks in the control group were fed a basal diet and the remainder were fed the basal diet supplemented with 200, 400, or 800 mg/kg curcumin. The experiment lasted for 21 D. Curcumin was present at 13.12 to 16.18 mg/g in the cecal digesta, 75.50 to 575.40 µg/g in jejunal mucosa, 35.10 to 73.65 µg/g in liver, and 7.02 to 7.88 µg/mL in plasma. The jejunal and hepatic contents of curcumin increased significantly (P < 0.05) in response to supplementation with 400 and 800 mg/kg of curcumin respectively, compared with 200 mg curcumin/kg group. There was a linear (P < 0.001) effect of dietary curcumin on relative abundance of SOD1, GPX1, CAT, HO-1, and Nrf2 transcripts, and a quadratic (P < 0.001) increase in the activities of GSH-Px and T-AOC in jejunal mucosa. The expression of CYP1A4, CYP2D17 increased and CYP1B1, CYP2A6 decreased linearly (P < 0.001) with dietary curcumin concentrations. In addition, dietary curcumin increased gene expression of GST, MRP6, and ABCB1 in jejunal mucosa. In conclusion, dietary supplementation with 200 to 800 mg/kg curcumin enhanced the accumulation of curcumin and its metabolites in jejunum as well as increasing the antioxidant capacity and detoxification potential, which play major roles in the protection of duck intestines against damage.

Utility and potential of rapid epidemic intelligence from internet-based sources.

OBJECTIVES: Rapid epidemic detection is an important objective of surveillance to enable timely intervention, but traditional validated surveillance data may not be available in the required timeframe for acute epidemic control. Increasing volumes of data on the Internet have prompted interest in methods that could use unstructured sources to enhance traditional disease surveillance and gain rapid epidemic intelligence. We aimed to summarise Internet-based methods that use freely-accessible, unstructured data for epidemic surveillance and explore their timeliness and accuracy outcomes. METHODS: Steps outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist were used to guide a systematic review of research related to the use of informal or unstructured data by Internet-based intelligence methods for surveillance. RESULTS: We identified 84 articles published between 2006-2016 relating to Internet-based public health surveillance methods. Studies used search queries, social media posts and approaches derived from existing Internet-based systems for early epidemic alerts and real-time monitoring. Most studies noted improved timeliness compared to official reporting, such as in the 2014 Ebola epidemic where epidemic alerts were generated first from ProMED-mail. Internet-based methods showed variable correlation strength with official datasets, with some methods showing reasonable accuracy. CONCLUSION: The proliferation of publicly available information on the Internet provided a new avenue for epidemic intelligence. Methodologies have been developed to collect Internet data and some systems are already used to enhance the timeliness of traditional surveillance systems. To improve the utility of Internet-based systems, the key attributes of timeliness and data accuracy should be included in future evaluations of surveillance systems.

Presenile (early ageing) changes in tissues of Kaschin-Beck disease and its pathogenetic significance.

The selenium level and activity of glutathione peroxidase in blood of children living in Kaschin-Beck disease (KBD) endemic areas were lower than that in nonendemic areas. KBD children were deficient in selenium, their lipid components, structure and function of the red cell membrane and cartilage tissue were abnormal. That is, the phospholipid (PL) content in the tissues of the patient was less than that of the controls in endemic and non-endemic areas. Especially as the phosphatidylcholine (PC) content decreased significantly, but sphingomyelin (SM) increased, the molar ratio of SM/PC and cholesterol (Ch)/PL increased. Increase of acanthocyte content was seen under the electron microscope and the fragility of erythrocytes was also increased. It indicated that there were membrane defects and membrane damage in KBD. At the same time, the sulfation extent of mucopolysaccharides in cartilage of patients was lower, and the collagen content was higher than that of controls. The presenile changes in lipid composition, structure and function of biomembranes and cartilage metabolism of KBD are very significant in studies on the aetiological pathogenesis of KBD and other ageing diseases.

Antileukemic activity of ungeremine and related compounds. Preparation of analogues of ungeremine by a practical photochemical reaction.

A number of alkoxypyrrolophenanthridinium salts and their analogues related to the antileukemic alkaloid ungeremine were prepared by a practical photochemical cyclization. The importance of the quaternary nitrogen atom and of alkoxy groups, the planarity of a molecule, and steric considerations relative to antileukemic activity are discussed.

Synthesis and antimalarial activity of 8-[(1-alkyl-4-aminobutyl)amino]-6-methoxy-4-methylquinolines.

Three analogues of the causal prophylactic antimalarial primaquine were prepared and their antimalarial activity was evaluated. 8-[(1-Ethyl-4-aminobutyl)amino]-6-methoxy-4-methylquinoline (2a) demonstrated activity against Plasmodium berghei in mice at 20 mg/kg, with all animals cured at 320 mg/kg, and is without toxicity at 640 mg/kg. It also possessed outstanding causal prophylactic activity against Plasmodium cynomolgi in rhesus monkeys at very low dosages.

Complete genomic organization and promoter analysis of the round-spotted pufferfish JAK1, JAK2, JAK3, and TYK2 genes.

We have previously reported the isolation of the JAK1 gene from the round-spotted pufferfish. In the present study, we cloned and characterized genomic sequences encoding pufferfish JAK2, JAK3, and TYK2, which are other members of JAK family. To our knowledge, this is the first report to demonstrate the existence of four JAK genes in fish. All pufferfish JAK genes except JAK1 are composed of 24 exons; JAK1 has an additional exon. A comparison of the exon-intron organization of these genes revealed that the splice sites of JAK genes are nearly identical. In addition, all pufferfish JAK genes have one intron in the 5' untranslated region. Taken together, these data suggest that the pufferfish JAK genes may have evolved from a common ancestor. By 5' rapid amplification of cDNA ends and sequence analysis, we deduced the promoter regions for all JAK genes and found they do not contain typical TATA or CCAAT boxes but rather numerous other potential binding sites for transcription factors. Interestingly, the TYK2 gene is linked to CDC37 in a head-to-tail manner with a small intergenic region of 292 bp. Within this region, there are two potential binding sites for transcriptional factors such as c-Myb and NF-IL6. The putative promoter regions of all JAK genes were tested either in a carp CF cell line or in zebrafish embryos using CAT or lacZ as reporter genes. Both assays confirmed the transcriptional activities of these promoters in vitro and in vivo.

Absence of mutagenicity of coralyne and related antileukemic agents: structural comparison with the potent carcinogen 7,12-dimethylbenz[a]anthracene.

The structural similarity between antileukemic alkaloid coralyne and the carcinogenic and antineoplastic hydrocarbon 7, 12-dimethylbenz[a]anthracene, as well as the similarity between the antileukemic alkaloid nitidine and the carcinogenic hydrocarbon 5-methylchrysene, prompted a mutagenicity evaluation of coralyne sulfoacetate, nitidine chloride, the 8-ethyl homolog of coralyne, nitidine methosulfate, and the tetramethoxy analog of nitidine by the Ames method against the histidine-auxotroph strains of Salmonella typhimurium TA-1537, TA-1538, TA-98, and TA-100; 7,12-dimethylbenz[a]anthracene was used as a reference standard. The mutagenicity of these antileukemic compounds was either completely eliminated or drastically reduced, but the mutagenic response was generally high for 7,12-dimethylbenz[a]anthracene. The results suggest that the presence of a quaternary nitrogen atom and alkoxy groups could be important in alleviating the mutagenicity of the parent mutagenic and carcinogenic hydrocarbons.

New tetraterpenoid from the soft coral Sarcophyton tortuosum.

A novel tetraterpenoid named methyl tortuoate C (1) has been isolated from the soft coral Sarcophyton tortuosum Tix.-Dur. The structure of 1 was determined on the basis of spectroscopic methods.

In situ zymography: a molecular pathology technique to localize endogenous protease activity in tissue sections.

Proteases play important roles in modulating a wide range of cellular functions, in the regulation of biologic processes, and in the pathogenesis of various diseases. Several molecular techniques are available to identify and characterize proteases in cells and tissues. Most of these techniques do not provide information on the activity of proteases in tissues. In situ zymography (ISZ) is a relatively low-cost technique that uses specific protease substrates to detect and localize specific protease activities in tissue sections. Used in combination with other techniques, ISZ provides data that further our understanding of the role of specific proteases in various pathologic and physiologic conditions. This review describes the general principle of ISZ and highlights the past and future applications of this technique in molecular pathology.

Effect of a lipidic extract from lepidium meyenii on sexual behavior in mice and rats.

OBJECTIVES: To determine the effect of oral administration of a purified lipidic extract from Lepidium meyenii (MacaPure M-01 and M-02) on the number of complete intromissions and mating in normal mice, and on the latent period of erection (LPE) in rats with erectile dysfunction. METHODS: Mice and rats were randomly divided into several experimental and control groups. A 10% ethanol suspension of M-01 and M-02 was orally administered for 22 days to the experimental groups according to the dosage specified by the experimental design. On day 22, 30 minutes after the dose was administered to the male mice, 2 virgin female mice were placed with 1 male mouse. The number of complete intromissions of each male mouse in 3 hours was recorded. In an assessment of 1 day of mating, each male mouse was cohabited with 5 estrous female mice overnight. The number of sperm-positive females was recorded. The LPE was measured to assess the sexual function in rats with erectile dysfunction. By using a YSD-4G multifunction instrument, an electric pulse at 20 V was applied to stimulate the rat's penis, and the duration from the start of the stimulus to full erection was measured in seconds as the LPE. RESULTS: In the normal male mice, the number of complete intromissions during the 3-hour period was 16.33 +/- 1.78, 46.67 +/- 2.39, and 67.01 +/- 2.55 for the control group, M-01 group, and M-02 group, respectively. In the assessment of mating, the number of sperm-positive females increased from 0.6 +/- 0.7 in the control group to 1.5 +/- 0.5 in the M-01 experimental group. The LPE of male rats with erectile dysfunction was 112 +/- 13 seconds with a regular diet (control group). The oral administration of M-01 at a dose of 180 or 1800 mg/kg body weight and M-02 at a dose of 45, 180, or 1800 mg/kg body weight reduced the LPE to 54 +/- 12 seconds, 54 +/- 13 seconds, 71 +/- 12 seconds, 73 +/- 12 seconds, and 41 +/- 13 seconds, respectively. The LPE of the surgical rats treated with M-01 at the lowest dose (45 mg/kg) was 121 +/- 12 seconds; thus, the change was not significant. CONCLUSIONS: Oral administration of M-01 and M-02 enhanced the sexual function of the mice and rats, as evidenced by an increase in the number of complete intromissions and the number of sperm-positive females in normal mice, and a decrease in the LPE in male rats with erectile dysfunction. The present study reveals for the first time an aphrodisiac activity of L. meyenii, an Andean Mountain herb.