[Effect of ursodeoxycholic acid with traditional Chinese medicine on biochemical response in patients with primary biliary cholangitis: a real-world cohort study].

Objective: To examine the effects of ursodeoxycholic acid combined with Traditional Chinese Medicine on biochemical response in patients with primary biliary cholangitis. Methods: According to the method of receiving treatment, 197 patients with primary biliary cholangitis were divided into Traditional Chinese Medicine plus Western medicine group (93 cases, 47.2%) and Western medicine group (104 cases, 52.8%). From the baseline date, the combined group was treated with ursodeoxycholic acid plus traditional Chinese medicine decoction or Chinese patent medicine for at least one month and the Western medicine group simply took ursodeoxycholic acid . Additionally, Traditional Chinese medicine decoction prescriptions were mainly Xiaoyaosan and Yinchenhao. Chinese patent medicine were restricted to Biejia Ruangan tablets, Fuzheng Huayu capsules, Jiuweigantai capsules and Yinzhihuang capsules, which were used to treat liver fibrosis and cholestasis. The primary efficacy endpoint was defined as ALP level < 1.67 × ULN and ≥ 15% decrease in ALP with baseline level and TBIL≤ULN after 12 months of treatment. Results: The overall biochemical response rate of patients was 35.0% (69/197). The response rate of TCM+ Western medicine group was 43.0% (40/93), and that of Western medicine group was 27.9% (29/104). The difference between the two groups was statistically significant (χ(2) = 4.936, P < 0.05). Further analysis showed that the Chinese and Western medicine group was superior to the Western medicine group alone in reducing γ-glutamyltransferase (GGT) and TBiL [the median decline were GGT: 160.1 U/L and 111.3 U/L (Z = -2.474, P < 0.05), TBiL: 5.2 umol/l and 3.1 umol/l (Z = -2.125, P < 0.05)]. Conclusion: UDCA combined with TCM therapy can remarkably improve the biochemical response rate in patients with PBC and distinctly decrease the TBIL and GGT levels than UDCA monotherapy.

Benzoic acid beneficially affects growth performance of weaned pigs which was associated with changes in gut bacterial populations, morphology indices and growth factor gene expression.

This study was conducted to investigate the effects of benzoic acid (BA) on growth performance, intestinal development and intestinal barrier function in weaned pigs. Ninety weaned pigs were randomly assigned to one of three treatments: a basal diet (CON), the basal diet supplemented with 2000 mg/kg benzoic acid (BA1) and 5000 mg/kg benzoic acid (BA2). At the end of days 14 and 42, six pigs per treatment were randomly selected to collect plasma and intestinal samples. Results showed that BA supplementation not only improved final body weight, daily growth and feed conversion ratio from days 15 to 42 and days 1 to 42, but also decreased the activity of plasma diamine oxidase (day 42) and the pH values of jejunal contents (day 14) (p < 0.05). Ileal Bacillus populations (day 14) were increased by BA, while Escherichia coli counts in the ileum and caecum (day 42) were decreased (p < 0.05). Higher Lactobacillus counts occurred in the ileum (day 14, 42) of BA1-fed piglets as compared to CON and BA2-fed piglets (p < 0.05). In addition, BA supplementation increased the ratio of villus height to crypt depth (day 14, 42) and decreased the crypt depth (day 14) (p < 0.05). Growth-stimulating factors (insulin-like growth factor-1, day 42; insulin-like growth factor-1 receptor, day 14, 42) and tight junction protein (occludin, day 14, 42; zonula occludens-1, day 42)-related gene mRNA levels were upregulated in the jejunum of piglets fed BA diets (p < 0.05). In conclusion, this study provides the first evidence that BA has beneficial effects on intestinal development and intestinal barrier function of weaned pigs, which can partly explain why growth performance of pigs was improved by dietary BA supplementation.

TP53 mutational status is predictive of pazopanib response in advanced sarcomas.

BACKGROUND: To investigate whether TP53 DNA mutational status impacts progression-free survival (PFS) in patients with advanced sarcomas (soft tissue sarcoma) treated with vascular endothelial growth factor receptors (VEGFR) inhibition. PATIENTS AND METHODS: We retrospectively reviewed 19 cases of patients treated at the Ohio State James Comprehensive Cancer Center with advanced sarcoma treated with VEGFR inhibition who also had next-generation sequencing of their tumors (via FoundationOne Heme panel). We evaluated TP53 as well as mutations that were observed in at least 20% of patients and evaluated its contribution to PFS using the Kaplan-Meier survival analysis of available radiology end points. RESULTS: Mutations that were observed in at least 20% of patients included TP53 and Rb1. Only TP53 was predictive of PFS in the context of VEGFR inhibition. The PFS of patients with TP53 mutations was significantly greater than TP53 wild-type tumors with the median PFS of 208 versus 136 days, respectively [P = 0.036, hazards ratio 0.38 (95% confidence interval 0.09-0.83)]. CONCLUSIONS: Mutations in TP53 may serve as a predictive biomarker of response to VEGFR inhibition in patients with advanced sarcoma. Larger, prospective studies are necessary to confirm these findings.

Influence of dietary nicotinic acid supplementation on lipid metabolism and related gene expression in two distinct broiler breeds of female chickens.

This study aimed to evaluate the influence of supplemental dietary nicotinic acid (NA) on lipid metabolism and hepatic expression of related genes in female chickens of two distinct broiler strains [Arbor Acres (AA) and Beijing-You (BJY)]. The treatments were arranged in a 2 × 4 factorial in a completely randomized design. Day-old females (n = 384) were allocated to four treatments with six cages per treatment and fed diets (basal contained approximately 25 mg NA/kg) supplemented with 0, 30, 60 and 120 mg NA/kg. A sample of 72 birds from each breed was slaughtered and sampled at their different market times (8 week for AA and 16 week for BJY). Arbor Acres broilers had thickness of subcutaneous fat plus the skin (SFS), and plasma concentration of low-density lipoprotein cholesterol (LDLC) and lower percentage of abdominal fat (PAF), plasma concentrations of TG, NEFA and adiponectin than the BJY line. The hepatic transcription of apolipoprotein A-I (ApoA-I), apolipoproteinB (ApoB), and adiponectin was significantly higher in AA broilers than in BJY broilers. In both breeds, BW, PAF, SFS, NEFA and TG were increased with increasing supplementation from 0 to 60 mg NA/kg, but then decreased slightly with 120 mg added NA/kg. With increasing supplementation, hepatic expression and plasma concentrations of adiponectin decreased from 0 to 60 mg added NA/kg and then increased with 120 mg added NA/kg. The expression of ApoA-I and ApoB mRNA showed linear response to dietary supplementation with NA. These findings indicate that: (i) supplementation of NA influenced the lipid metabolism and related gene expression; (ii) when supplemented with 120 mg NA/kg, some pharmacologic actions on lipid metabolism appeared; and (iii) changes in BW and fat deposition appeared to be associated with hepatic expression of adiponectin.

Effect of dietary supplemental nicotinic acid on growth performance, carcass characteristics and meat quality in three genotypes of chicken.

The effects of dietary supplemental nicotinic acid (NA) on growth performance, carcass characteristics and meat quality were investigated in three genotypes of chicken. Fast-growing AA (Arbor Acres) broilers were compared with two genotypes of a slow-growing local breed, Beijing-You, that had undergone selection for and against intramuscular fat content respectively (BJY+IMF and BJY-IMF). The treatments were arranged 3×4 factorial completely randomized design. Day-old females (n=624) were allocated to four treatments with six replicates per treatment and fed diets (basal contained ~25 mg NA/kg) supplemented with 0, 30, 60 and 120 mg NA/kg. A sample of 72 birds from each genotype was slaughtered at market time (8 weeks of age for AA and 16 weeks of age for BJY). The breast muscles of AA broilers were darker, had less redness and yellowness, lower drip loss and higher shear force as compared to the BJY genotypes (p<0.01). The highest drip loss and the lowest shear force among the three genotypes were apparent in BJY+IMF (p<0.01). Increasing supplementation from 0 to 60 mg NA/kg tended to increase average daily gain (ADG), average daily feed intake, width of intermuscular fat band, thickness of subcutaneous fat (including skin) and percentage of abdominal fat but, for most variables, values decreased slightly with 120 mg NA/kg. Increasing supplementation to 60 mg NA/kg decreased (quadratic, p<0.001) drip loss, but it increased at 120 mg NA/kg. The present results indicate that (i) the AA broilers fed corn-soybean meal based-diets require approximately 60 mg NA/kg to maximize ADG and meat product yield and decrease the drip loss of breast muscle; (ii) the addition of 30 mg NA/kg meets the requirement of BJY genotypes; and (iii) there seems to be no beneficial effect of NA supplementation on chicken meat quality except for limiting the drip loss.

Effects of dietary vitamin E on immunological stress of layers and their offspring.

In the present study, two experiments were conducted to evaluate the effect of vitamin E (VE) supplementation of a commercial layer diet on the laying performance and immunological stress responses of hens and their offspring. In experiment 1, responses to increased dietary VE levels were evaluated on 180 White Leghorn layers between 20 and 35 weeks of age. There were three levels of VE in the diets (0, 40 and 100 IU/kg) and five replicates per treatment, each containing 12 hens. Results showed that the high level of VE supplementation (100 IU/kg) had a beneficial effect on feed intake and feed efficiency of hens (p < 0.05), compared with the VE-deficient or low-level group. In experiment 2, 540 female progeny from the VE-treated hens in experiment 1 were used. The experimental design consisted of three levels of VE supplementation (the same as their mothers') × 3 vaccinating routines, the first vaccination being administered on day 5, 8 or 11. All vaccines and the subsequent vaccinating intervals were identical. In the interim of the experiment, each bird was injected celiacly with Escherichia coli lipopolysaccharide (LPS). The results showed that antibody titres against Newcastle disease virus (NDV) or avian influenza virus (AIV) and the plasma concentration of interleukin (IL)-1 were increased by the high level of VE supplementation. There were significant effects of the day of initial immunization with infection bursal disease on the NDV and AIV antibody titre, H/L ratio and plasma concentration of corticosterone and IL-1 before and after injecting LPS, suggesting the occurrence of immunological stress. There was also significant interaction between VE and vaccination routine on the immune functions of experimental birds. Considered together with the results of experiment 1, VEs biological function appeared to be dose-dependent, especially with regard to its positive effect on the immune responses of young chickens.

Effect of dietary omega6/omega3 on growth performance, carcass traits, meat quality and fatty acid profiles of Beijing-you chicken.

The effects of varying the omega6 to omega3 fatty acid ratio (omega6/omega3) of diets on growth performance, carcass traits, meat quality and fatty acid composition of breast muscle were investigated in Beijing-you chickens grown to 92 days. A total of 360 one-day-old female BJY chickens were fed diets containing 0%, 0.12%, 0.42%, 1.00% or 1.97% linseed oil replacing equal weights of maize oil to make dietary omega6/omega3 to be approximately 30:1, 20:1, 10:1, 5:1 and 2.5:1. Subcutaneous fat thickness and intramuscular fat content increased significantly in birds fed up to 10:1 omega6/omega3. a* values (redness of meat, dimension of the CIELAB-system) progressively increased as the diets contained increasing omega3 content, up to the 10:1 omega6/omega3.The changes in b* (yellowness of meat, dimensions of the CIELAB-system) were also significant but the pattern was almost the reverse of changes in a*. Shear force increased significantly as dietary omega6/omega3 was reduced from 30:1 to 5:1. Decreasing the dietary omega6/omega3 clearly decreased the content in breast muscle of C20:1 and C22:1, but increased that of C24:1. C20:4, C20:5 and C22:5, increased significantly by decreasing the dietary omega6/omega3, and the birds fed the 10:1 diet had higher contents of C22:6 than other treatments. This study has clearly demonstrated that decreasing the dietary omega6/omega3, increases the deposition of desirable omega3 and omega6 long chain PUFA in the edible tissue, thereby achieving nutritionally enriched meat.

Influence of dietary vitamin E supplementation on meat quality traits and gene expression related to lipid metabolism in the Beijing-you chicken.

1. The effects of dietary vitamin E (DL-alpha-tocopheryl acetate) on carcase and meat quality, oxidative stability, fatty acid composition of muscle lipids, and gene expression related to lipid metabolism were studied in Beijing-you chickens. 2. A total of 360 female birds were distributed among 6 treatments, containing 6 replicates, each of 10 birds. The feed for each treatment was supplemented with vitamin E (0, 10, 50, 100, 150, or 200 mg/kg feed). At 120 d, 30 birds from each treatment were slaughtered to examine the effect of dietary vitamin E supplementation on evaluated traits. 3. The results showed that supplemental vitamin E in diet significantly increased alpha-tocopherol contents of breast and thigh muscles, reduced the drip loss and improved tenderness but did not influence carcase yield, meat colour or pH value 24 h after slaughter. 4. Thiobarbituric acid reactive substance (TBARS) values decreased with increase in dietary vitamin E, and the addition of 100 mg/kg or more vitamin E had a beneficial effect on oxidative stability as indicated by TBARS values during storage up to 7 d. 5. Dietary vitamin E supplementation significantly altered fatty acid composition of breast muscle. Supplementing with 200 mg/kg vitamin E led to lower saturated fatty acids and greater polyunsaturated fatty acids proportions in breast muscle than control and 10 mg/kg vitamin E treatments. 6. Vitamin E supplementation significantly inhibited expression of the cytosolic phospholipase A(2) gene (cPLA(2)) in breast muscle, while enhancing that of the peroxisome proliterator-activated receptor beta (PPAP-beta) and heart fatty acid binding protein genes (H-FABP). The results indicate that dietary supplementation with vitamin E increased lipid stability in muscle and improved meat quality and fatty acid composition, probably by its influence on the expression of genes related to lipid metabolism.

ATP7B antisense oligodeoxynucleotides increase the cisplatin sensitivity of human ovarian cancer cell line SKOV3ipl.

The objective of this study was to investigate the effect of ATP7B antisense oligodeoxynucleotides (ASODNs) on regulating the sensitivity to cisplatin in ovarian carcinoma cell line SKOV3ip1. The ATP7B ASODNs and the corresponding sense oligodeoxynucleotide (SODN) as control were transfected into SKOV3ip1 cells by lipofectamine-2000. The changes of ATP7B were detected by reverse transcription-polymerase chain reaction, flow cytometry, and Western blotting. The survival rate of the SKOV3ip1 cells was assessed by MTT assay. Compared with nontransfected cell, the transfer of ASODN/lipofectin (LF) into SKOV3ip1 cells resulted in (1) 73.70% and 48.30% reduction of ATP7B in messenger RNA and protein, respectively, (2) an obviously decreased intracellular fluorescence intensity from 79.42 to 50.87 (P < 0.01), and (3) a decreased IC(50) value for cisplatin from 126.63 to 80.90 micromol/L (P < 0.01), while no significant changes were detected for groups treated with SODN/LF and LF only. ASODN transfection can inhibit the expression of ATP7B and increase the cisplatin sensitivity in SKOV3ip1 cells.

Effect of conjugated linoleic acid on growth performances, carcase composition, plasma lipoprotein lipase activity and meat traits of chickens.

1. The effects of dietary conjugated linoleic acid isomers (CLAs) on productive traits, carcase yield and meat quality were investigated in Beijingyou (Chinese) chickens. A total of 360 male chicks were allocated to 5 dietary treatments (0.00, 0.25, 0.50, 1.00 and 2.00% CLA) and fed for 126 d. 2. The results showed that CLA supplementation did not significantly influence body weight, but increased feed conversion and decreased intramuscular fat in breast and thigh muscles. Mortality was significantly higher in the control group. 3. The addition of 1.0 and 2.0% CLA decreased abdominal fat percentages. At CLA dietary levels greater than 0.5%, lipoprotein lipase activity in plasma was significantly decreased. 4. Hunter L* and a* values were not significantly affected by CLA supplementation. However, Hunter b* values were lower in chickens supplemented at levels greater than 0.5% CLA. Supplementing diets with CLA modified the fatty acid composition of breast muscle. The proportions of CLA, saturated and polyunsaturated fatty acids were increased whereas the proportion of monounsaturated fatty acids was decreased.

An integrated healthcare enterprise information portal and healthcare information system framework.

The paper presents an integrated, distributed Healthcare Enterprise Information Portal (HEIP) and Hospital Information Systems (HIS) framework over wireless/wired infrastructure at National Taiwan University Hospital (NTUH). A single sign-on solution for the hospital customer relationship management (CRM) in HEIP has been established. The outcomes of the newly developed Outpatient Information Systems (OIS) in HIS are discussed. The future HEIP blueprints with CRM oriented features: e-Learning, Remote Consultation and Diagnosis (RCD), as well as on-Line Vaccination Services are addressed. Finally, the integrated HEIP and HIS architectures based on the middleware technologies are proposed along with the feasible approaches. The preliminary performance of multi-media, time-based data exchanges over the wireless HEIP side is collected to evaluate the efficiency of the architecture.

Novel antihyperglycemic terpenoid-quinones from Pycnanthus angolensis.

Two new compounds, pycnanthuquinone A (1) and pycnanthuquinone B (2), were isolated from leaves and stems of the African plant, Pycnanthus angolensis (Welw.) Warb (Myristicaceae), by bioassay-guided fractionation of an ethanolic extract using a diabetic mouse model. Pycnanthuquinones A and B are the first representatives of a novel terpenoid-type quinone skeleton, and both compounds possess significant antihyperglycemic activity.

New iridoids from the medicinal plant Barleria prionitis with potent activity against respiratory syncytial virus.

Two new iridoid glycosides (1 and 2), together with the known compounds barlerin (3) and verbascoside (4), were isolated from Barleria prionitis. The new iridoid glycosides were determined to be 6-O-trans-p-coumaroyl-8-O-acetylshanzhiside methyl ester (1) and its cis isomer (2) by using spectroscopic, especially 2D NMR, data. A 3:1 mixture of 1 and 2 was shown to have potent in vitro activity against respiratory syncytial virus (EC50 2.46 microgram/mL, IC50 42.2 microgram/mL).

Antiviral phenylpropanoid glycosides from the medicinal plant Markhamia lutea.

Three new phenylpropanoid glycosides, named luteoside A (3), luteoside B (4), and luteoside C (5), were isolated together with the known compounds verbascoside (1) and isoverbascoside (2) from the roots of the medicinal plant Markhamia lutea. The structures of the new compounds were determined to be 1-O-(3, 4-dihydroxyphenyl)ethyl beta-D-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-4-O- caffeo yl-6-acetyl-beta-d-glucopyranoside, 1-O-(3,4-dihydroxyphenyl)ethyl beta-d-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-6-O- caffeo yl-beta-d-glucopyranoside, and 1-O-(3,4-dihydroxyphenyl)ethyl beta-D-apiofuranosyl(1-->2)-alpha-l-rhamnopyranosyl(1-->3)-6-O- ferulo yl-beta-d-glucopyranoside, respectively, on the basis of chemical and spectroscopic data. All five phenylpropanoid glycosides exhibited potent in vitro activity against respiratory syncytial virus.

Acetogenins from seeds of Annona reticulata.

Chromatography of an ethyl acetate extract of seeds of Annona reticulata led to the isolation of a new cytotoxic gamma-lactone acetogenin, cis-/trans-isomurisolenin, along with six known cytotoxic acetogenins, annoreticuin, annoreticuin-9-one, bullatacin, squamocin, cis-/trans-bullatacinone and cis-/trans-murisolinone. Structures of these compounds were established by means of mass and related spectral experiments. Some of the compounds isolated, showed potent cytotoxicities against Hep. 2,2,15, Hep. G2, KB and CCM2, four cancer cell-lines.

Two new lignans with activity against influenza virus from the medicinal plant Rhinacanthus nasutus.

Two new lignans, rhinacanthin E (1) and rhinacanthin F (2), were isolated from the aerial parts of the plant Rhinacanthus nasutus. Their structures were established by detailed spectroscopic analysis. These compounds show significant antiviral activity against influenza virus type A.

Molecular cloning and analysis of two subunits of the human TFIID complex: hTAFII130 and hTAFII100.

Transcription factor TFIID is a multiprotein complex composed of the TATA box-binding protein (TBP) and multiple TBP-associated factors (TAFs). TFIID plays an essential role in mediating transcriptional activation by gene-specific activators. Numerous transcriptional activators have been characterized from mammalian cells; however, molecular analysis of the components of mammalian TFIID has been incomplete. Here we describe isolation of cDNAs encoding two TAF subunits of the human transcription factor TFIID. The first cDNA is predicted to encode the C-terminal 947 residues of the 130-kDa human TAF subunit, hTAFII130. The second cDNA encodes the C-terminal 801 residues of the 100-kDa subunit, hTAFII100. Recombinant TAFs expressed in human cells by transient transfections are capable of associating with the endogenous TAFs and TBP to form a TFIID complex in vivo. Protein binding experiments demonstrate that hTAFII130, like its Drosophila homolog dTAFII110, interacts with the glutamine-rich activation domains of the human transcription factor Sp1. Furthermore, hTAFII130 shows reduced binding to the Sp1 mutants with impaired ability to activate transcription, suggesting a role for hTAFII130 as a direct coactivator target for Sp1.

Two new naphthoquinones with antiviral activity from Rhinacanthus nasutus.

Two new naphthoquinones, rhinacanthin-C (1) and rhinacanthin-D (2), exhibit inhibitory activity against cytomegalovirus (CMV), with EC50 values of 0.02 and 0.22 microgram/mL, respectively, against human CMV. They were isolated from the medicinal plant Rhinacanthus nasutus (Acanthaceae). The structures of the compounds were determined by analysis of their spectroscopic data, in particular, 2D NMR.

[A study on the regulation of ACTH secretion in rat pituitary cells].

In addition to method of ACTH RIA, a rat pituitary cell perfusion system was developed for the assessment of pituitary cells in stimulating and inhibiting ACTH secretion induced by some substances. Hypothalamic extract stimulated the ACTH secretion in a dose-dependent manner. AVP, cAMP, Ca2+, K+, noradrenaline, metoclopramide and haloperidol also had some stimulating effect. Dexamethasone and dopamine inhibited the basal ACTH secretion of pituitary cell and antagonized the effect of the various stimulating substances. Cyproheptadine could antagonize the effect of some of the stimulating substances while GABA had no marked inhibiting effect.

[Change in serum growth hormone in aged men and effect of kidney-warming and yang-restoring drugs].

Basal and sleeping levels of serum growth hormone (GH) were measured in aged men and young men. GH levels after an intravenous bolus of growth hormone releasing hormone (1 microgram/kg) were also determined in healthy aged men with mild Kidney-Yang deficiency. The effect of Chinese herbs with Kidney-warming and Yang-restoring function was observed. The basal GH value in aged men was not significantly different when compared with young men, but the GH value during sleep evidently decreased (P less than 0.05). The response of GH to GRF was obviously decreased as compared with young people. The GH level following GRF stimulation was significantly different from that of young men. The Kidney-warming and Yang-restoring Chinese herbs could alleviate the symptoms of Kidney-Yang deficiency in aged men. The sleep value of GH and response of GH to GRF were increased after taking Chinese herbs. It suggested that the decrease of pituitary reserve might probably be the pathogenesis of Kidney deficiency. Together with the results of another animal experiments, the authors presumed that the Chinese herbs with Kidney-warming and Yang-restoring characteristics might effect through the increase of hypothalamic dopamine and the subsequent improvement of pituitary hormone reserve.